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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the effects of using absorbable synthetic suture material compared to catgut for perineal repair in terms of short-term pain, need for analgesia, suture dehiscence, and long-term pain? Please answer this question based on the information provided below:
[A comparison between chromic catgut and polyglycolic acid sutures in episiotomy repair (author's transl)].
Polyglycolic acid sutures (Dexon) were compared to chromic catgut sutures in episiotomy repair. When polyglycolic acid sutures were used, the degree of postpartum perineal pain was approximately half as great, and the incidence of dehiscence of episiotomy was 3--5 times greater in the chromic catgut group. The cosmetic results 3 months postpartum were clearly better by using Dexon sutures, especially when the perineal skin was closed by a continuous intracutaneous suture.
A trial of polyglycolic acid and chromic catgut sutures in episiotomy repair.
A comparison between catgut and polyglycolic acid sutures in episiotomy repair.
The Ipswich Childbirth Study: 2. A randomised comparison of polyglactin 910 with chromic catgut for postpartum perineal repair.
OBJECTIVE: To compare polyglactin 910 sutures with chromic catgut sutures for postpartum perineal repair.
DESIGN: A stratified randomised controlled trial, using a 2 x 2 factorial design.
SETTING: The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994.
SAMPLE: 1780 women who had sustained an episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery.
METHODS: Policies of repair with polyglactin 910 or chromic catgut were compared. Both groups were assessed by a research midwife completing questionnaires at 24 to 48 hours and at ten days postpartum, and by self-completed questionnaires at three months after birth.
MAIN OUTCOME MEASURES: 1. 24 to 48 hours postpartum: perineal pain, healing; 2. ten days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse.
RESULTS: Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. The two groups were similar at trial entry. Significantly fewer women allocated to the polyglactin 910 reported pain in the previous 24 hours at both 24 to 48 hours (59% vs 67%; RR 0.89, 95% CI 0.83-0.95; 2P < 0.01), and ten days (24% vs 29%; RR 0.81, 95% CI 0.69-0.95; 2P = 0.01). At three months postpartum there was no clear difference between the groups in terms of perineal pain, dyspareunia or failure to resume pain-free intercourse. More women in the polyglactin 910 group reported that some suture material had been removed (12% vs 7%; RR 1.62, 95% CI 1.19-2.21; 2P < 0.01). Three women in the polyglactin 910 group had required resuturing compared with ten in the chromic catgut group (RR 0.30; 95% CI 0.08-1.09; 2P = 0.1).
CONCLUSIONS: Using polyglactin 910 rather than chromic catgut for perineal repair leads to about one fewer women among every 20 having perineal pain and using analgesia ten days postpartum. Its only apparent disadvantage is that more women, again estimated as 1 in 20, report having material removed during healing. Data from this and other trials suggest that for every 100 women repaired with a polyglycolic acid-based material, about one fewer will require resuturing.
The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma.
Commonly used suture materials and techniques for perineal repair following vaginal delivery were compared in a randomized controlled trial involving 1574 women. Three comparisons were made using a modified factorial design. In the comparison of teflon-coated polyglycolic acid (Dexon plus) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short-term analgesia being required in association with polyglycolic acid. Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk, although silk repair required more packets of material and was associated with delay in resuming sexual intercourse; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing. There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin.
Polyglycolic acid and catgut sutures, with and without oral proteolytic enzymes, in the healing of episiotomies.
Polyglycolic acid (PGA) sutures and traditional catgut were compared in 190 patients undergoing episiotomy. Each group was also randomly allocated to a double blind comparison of therapy with oral proteolytic enzymes (Chymoral) and placebo. The combination of Chymoral and polyglycolic acid sutures was shown to reduce the level of pain, assessed subjectively, and there was a significant reduction in analgesic requirements in the Chymoral/PGA group.
Evaluation of post-episiorrhaphy pain: polyglycolic acid vs catgut sutures.
Options:
A: Absorbable synthetic sutures result in less short-term pain, less need for analgesia, less suture dehiscence, and significantly less long-term pain.
B: Absorbable synthetic sutures result in less short-term pain, less need for analgesia, less suture dehiscence, but no significant difference in long-term pain.
C: Absorbable synthetic sutures result in more short-term pain, more need for analgesia, more suture dehiscence, and significantly more long-term pain.
D: Absorbable synthetic sutures result in no difference in short-term pain, need for analgesia, suture dehiscence, or long-term pain.
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B
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1
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of bed rest in hospital for women with suspected impaired fetal growth compared to ambulatory management? Please answer this question based on the information provided below:
The effect of bedrest in hospital on fetal outcome in pregnancies complicated by intra-uterine growth retardation.
A prospective study was made to evaluate whether bedrest in hospital is beneficial in pregnancies where intra-uterine growth retardation (IUGR) was suspected. Diagnosis was based on routine fetometry at 32 weeks of gestation, in conjunction with general ultrasound screening. 107 patients with suspected IUGR-pregnancies were divided into two groups, 49 in a hospital bedrest group and 58 in an 'out-patient' group. Fifteen women in the bedrest group refused hospitalization, and 8 women in the out-patient group had to be hospitalized for medical reasons other than suspected growth retardation, leaving 79% of the women in their allocated group. The women in the bedrest group were hospitalized for a mean duration of 29.2 days (range 5-54). The results suggest that bedrest in hospital is not beneficial, either to fetal growth or to pregnancy outcome.
Options:
A: Bed rest in hospital significantly improved fetal growth parameters and neonatal outcomes.
B: Bed rest in hospital significantly worsened fetal growth parameters and neonatal outcomes.
C: There were no significant differences in fetal growth parameters and neonatal outcomes between bed rest in hospital and ambulatory management.
D: Bed rest in hospital was found to be harmful to both the mother and the fetus.
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C
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2
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness of betamimetic therapy for suspected impaired fetal growth in terms of fetal growth and perinatal outcomes? Please answer this question based on the information provided below:
Long-term hospitalization and beta-mimetic therapy in the treatment of intrauterine growth retardation of unknown etiology.
A group of 98 third trimester pregnant women whose ultrasonographic studies raised the suspicion of intrauterine fetal growth retardation was studied. The patients were randomly assigned to two groups: Group A (Treatment group: 44 patients) and Group B (Control group: 54 patients). All patients were admitted to the hospital upon diagnosis for baseline evaluation. Those in Group A remained in the hospital until delivery (mean stay 15 +/- 5 days) and received treatment with 10 mg/t.i.d. of p.o. ritodrine. Group B patients were discharged after an average stay of 7 +/- 3 days. This group was not treated with ritodrine, and they were seen weekly in an outpatient setting. The prevalence of low-birth-weight infants for their gestational age was 47.73% in the treatment group and 40.74% in the control group. Of the deliveries in the treatment group, 40.9% were induced (half for fetal indications). In the control group 35.18% of the induced labors was (47.35% for fetal indications). Of the cases in the treatment group 18.18% were delivered by cesarean section, of which 62.5% were performed for fetal distress. The control group showed similar figures: 16.66% cesarean sections with 77.7% of them done for fetal distress. We observed an incidence of 20.45% of acute fetal distress in the study group against 12.96% in the control group. Such a difference is not statistically significant. The group under study demonstrated a rate of 6.82% pathological pH value in the umbilical artery, while the rate of abnormal values in the control group was 18.52%. In both groups, the greatest percentage of acidotic pH was observed in patients with IGR.(ABSTRACT TRUNCATED AT 250 WORDS)
Options:
A: Betamimetic therapy significantly improved fetal growth and reduced neonatal morbidity and mortality.
B: Betamimetic therapy had no significant effect on fetal growth, neonatal morbidity, or mortality.
C: Betamimetic therapy significantly increased the risk of low birth weight and other adverse outcomes.
D: Betamimetic therapy showed mixed results, with some studies indicating benefits and others indicating harm.
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B
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3
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the use of prophylactic betamimetic therapy during the second stage of labour on perinatal outcomes? Please answer this question based on the information provided below:
The effect of intravenous ritodrine on the acid-base status of the fetus during the second stage of labour.
A progressive fetal respiratory acidosis occurs in the second stage of labour. A double-blind controlled trial showed that the intravenous infusion of Ritodrine abolished this.
Options:
A: Prophylactic betamimetic therapy significantly reduced the need for forceps deliveries and improved neonatal outcomes.
B: Prophylactic betamimetic therapy had no significant effect on the need for forceps deliveries, postpartum haemorrhage, neonatal irritability, feeding slowness, umbilical arterial pH values, or Apgar scores at 2 minutes.
C: Prophylactic betamimetic therapy was associated with an increase in forceps deliveries and had no clear effects on postpartum haemorrhage, neonatal irritability, feeding slowness, umbilical arterial pH values, or Apgar scores at 2 minutes.
D: Prophylactic betamimetic therapy significantly improved placental blood flow and fetal oxygenation, leading to better perinatal outcomes.
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C
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4
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness and tolerance of different antibiotics for treating genital Chlamydia trachomatis infection in pregnant women? Please answer this question based on the information provided below:
Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.
OBJECTIVE: To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy.
METHODS: Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy. Side effects, compliance, and treatment efficacy were assessed.
RESULTS: One hundred six women were enrolled, and eighty-five women completed the protocol. Significantly fewer gastrointestinal side effects were noted in the azithromycin group than in the erythromycin group (11.9% versus 58.1%, P < or = .01). Enhanced compliance was noted with azithromycin, because it was given in a single observed dose. Similar treatment efficacy was noted between azithromycin and erythromycin (88.1% versus 93.0%, P > .05).
CONCLUSION: Compared with erythromycin, azithromycin is associated with significantly fewer gastrointestinal side effects in pregnancy. This association, along with the ease of administration and similar efficacy, suggests that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy.
Randomised comparison of amoxycillin and erythromycin in treatment of genital chlamydial infection in pregnancy.
Erythromycin, the standard treatment for chlamydial infection in pregnant women, commonly causes side-effects, which limits its efficacy. In a randomised, double-blind study, we compared amoxycillin with erythromycin in this setting. 210 pregnant women with Chlamydia trachomatis infection were randomly assigned 7 days' treatment with amoxycillin (500 mg three times daily) or erythromycin (500 mg four times daily). Control cultures were obtained 21 days after treatment, during late pregnancy, and from the infant within a week of birth. Treatment was judged a failure if any post-treatment culture was positive or if the patient had to stop therapy because of severe side-effects. 11 women (5.2%) were lost to follow-up. 1 (of 100) amoxycillin-treated women had to stop treatment because of severe side-effects compared with 12 (of 99) erythromycin-treated women (p = 0.002). 1 woman in the amoxycillin group had a positive culture at the third-trimester examination. No positive post-treatment culture was found in the erythromycin group. Severe gastrointestinal side-effects were more common in women who received erythromycin (31 vs 6%, p < 0.001). The overall failure rate was therefore 2% in the amoxycillin group and 12% in the erythromycin group (p = 0.005). These results suggest that amoxycillin is an acceptable alternative to erythromycin for C trachomatis infection in pregnant women.
Comparative efficacy of clindamycin versus erythromycin in eradication of antenatal Chlamydia trachomatis.
Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity. Erythromycin, the only drug recommended for treatment during pregnancy, is often poorly tolerated, thus preventing successful cure. We have done a prospective, randomized, double-blind, placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia. A total of 126 patients with documented cervical infection were enrolled before 24 weeks' gestation to receive clindamycin (450 mg), erythromycin (333 mg), or placebo orally four times daily for 14 days. Partners received doxycycline, 100 mg, twice daily for 7 days. Both clindamycin and erythromycin were effective agents with cure rates of 92.7% and 83.8%, respectively. Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy (23.1% (9/39) vs. 2.4% (1/41), p less than 0.02) whereas clindamycin was not. Patients who experienced side effects were more likely to be poorly compliant (p less than 0.03) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant (p less than 0.002). Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later.
Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy.
OBJECTIVE: To compare azithromycin and erythromycin in regard to side effects, intolerance, and cure rate in a pregnant population with chlamydial cervicitis.
METHODS: Thirty women were randomized to receive either erythromycin, 500 mg orally four times a day for 7 days, or azithromycin, 1 g orally as one dose. All subjects completed questionnaires identifying the incidence of nausea, vomiting, diarrhea, abdominal pain, and anorexia. Post-treatment cultures were taken from all subjects.
RESULTS: All subjects receiving erythromycin reported two or more gastrointestinal side effects, versus none in the azithromycin group (P < .001). Five of 15 subjects in the erythromycin treatment arm were intolerant to the 500-mg dose given four times a day, compared to none in the azithromycin group (P < .025), so the dosage was lowered to 250 mg four times a day to complete the course. Repeat cervical testing demonstrated similar cure rates for both medications: 100 and 93% (14 of 15) for azithromycin and erythromycin, respectively.
CONCLUSION: These data suggest that azithromycin is a valid treatment option in pregnant patients who cannot tolerate erythromycin because of side effects.
Randomized Clinical Trial of Azithromycin vs. Erythromycin for the Treatment of Chlamydia Cervicitis in Pregnancy.
OBJECTIVE: The purpose of this study was to prospectively test the null hypothesis that there is no difference in the clinical effectiveness of azithromycin and erythromycin for the treatment of chlamydia cervicitis in pregnancy.
METHODS: All antepartum obstetrical patients underwent routine screening for chlamydia cervicitis using a DNA probe assay (Gen-Probe Pace, San Diego, CA). Women who tested positive for chlamydia cervicitis were prospectively randomized to receive either azithromycin 1 g orally at enrollment, or erythromycin 500 mg orally 4 times a day for 7 days. Sexual partners were referred to the county health department for evaluation and treatment. A test of cure was repeated in 2 weeks. RESULTS were analyzed by chi-square analysis and Fisher's exact test when indicated.
RESULTS: One hundred forty women tested positive for chlamydia cervicitis and agreed to randomization. There were 4 (6.2%) treatment failures in the azithromycin group and 18 (27.7%) in the erythromycin group (P = 0.005). Gastrointestinal side effects were reported by 42 (65.5%) of the women taking erythromycin, but only 12 (19.4%) of those taking azithromycin (P < 0.002). Gastrointestinal side effects and resultant noncompliance were significantly related to treatment failure with erythromycin.
CONCLUSIONS: The findings of this study support the conclusion that a single dose of azithromycin is a significantly more effective and better tolerated treatment regimen for chlamydia cervicitis in pregnancy than erythromycin which is currently recommended.
Double-blind randomized study comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy.
OBJECTIVE: To compare the efficacy and patient tolerance of amoxicillin to that of erythromycin in the treatment of lower genital tract chlamydia infections during pregnancy.
METHODS: A double-blind, randomized study was conducted comparing oral amoxicillin 500 mg three times daily versus oral erythromycin 500 mg four times daily for 7 days. One hundred forty-three women with positive cervical cultures for chlamydia at less than 36 weeks' gestation were enrolled. A test-of-cure culture was obtained 4 weeks after entry into the study and side effects were assessed. Success of the regimen was defined as completing the course of medication and having a negative test-of-cure culture.
RESULTS: Thirty of the 65 women in the erythromycin group (46.1%) developed symptoms while taking the medication and 15 of them were unable to continue treatment (23.1%). In contrast, five of the 65 women (7.7%) in the amoxicillin group became symptomatic, with only one of these patients intolerant of the side effects (1.5%) (P < .001). Of the 50 patients in the erythromycin group who were able to complete their course of medication, only three had a positive test of cure (6.0%). In comparison, nine of the 64 patients (14.1%) taking amoxicillin who completed their course had positive cultures at test of cure. This difference was not statistically significant (P = .14). Forty-seven of the 65 patients (72.3%) in the erythromycin group successfully completed their regimen, compared to 55 of the 65 women (84.6%) in the amoxicillin group. This difference was not statistically significant.
CONCLUSIONS: These findings suggest that amoxicillin is a reasonable alternative for the treatment of chlamydia in pregnant patients intolerant to erythromycin. The incidence of side effects and intolerance to therapy for amoxicillin are less than those for erythromycin.
Double-Blind Placebo-Controlled Treatment Trial of Chlamydia trachomatis Endocervical Infections in Pregnant Women.
OBJECTIVE: The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and/or low birth weight.
METHODS: Pregnant women between the 23rd and 29th weeks of gestation were randomized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo. The trial continued until the end of the 35th week of gestation.
RESULTS: When the results were examined without regard to study site, erythromycin had little impact on reducing low birth weight (8% vs. 11%, P = 0.4) or preterm delivery (13% vs. 15%, P = 0.7). At the sites with high persistence of C. trachomatis in the placebo-treated women, low birth weight infants occurred in 9 (8%) of 114 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.04) and delivery <37 weeks occurred in 15 (13%) of 115 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.4).
CONCLUSIONS: The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis. Due to the high clearance rate of C. trachomatis in the placebo group, these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight.
Randomized trial of erythromycin and azithromycin for treatment of chlamydial infection in pregnancy.
OBJECTIVE: The purpose of this study was to compare erythromycin and azithromycin in the treatment of chlamydial cervicitis during pregnancy with regard to efficacy, side effects, and compliance.
METHODS: In a prospective manner, 48 pregnant patients with cervical chlamydial infections diagnosed by routine screening tests were randomly assigned to receive either erythromycin, 500 mg q.i.d. for 7 days (N = 24), or azithromycin, 1 g as a one-time dose (N = 24). All sexual partners were given prescriptions for doxycycline, 100 mg b.i.d. for 7 days. The treatment efficacy was assessed by follow-up chlamydia testing 3 weeks after the therapy was completed. The side effects, intolerance to therapy, and overall compliance were evaluated by means of a standardized posttreatment questionnaire.
RESULTS: There was no significant difference in cure rates noted between the erythromycin group and the azithromycin group (77% vs. 91%, respectively; P = 0.24). Gastrointestinal side effects were reported more frequently among patients treated with erythromycin compared with patients treated with azithromycin (45% vs. 17%, respectively; P = 0.004). The patients who received erythromycin reported intolerance to therapy secondary to side effects more frequently than patients who received azithromycin (23% vs. 4%, respectively; P = 0.07). Furthermore, the patients in the azithromycin group were more likely to complete their course of therapy as prescribed than the patients in the erythromycin group (100% vs. 61%, respectively; P = 0.002).
CONCLUSIONS: Azithromycin is efficacious and well tolerated for the treatment of chlamydial cervicitis in pregnancy. Erythromycin, though efficacious, is poorly tolerated, as demonstrated by the number of patients reporting significant side effects during the course of therapy. Since the cost of azithromycin is comparable to that of generic erythromycin, the present study supports the use of azithromycin as an alternative to erythromycin for the treatment of chlamydial cervicitis in pregnancy.
Randomized trial of erythromycin and azithromycin for treatment of chlamydial infection in pregnancy.
OBJECTIVE: The purpose of this study was to compare erythromycin and azithromycin in the treatment of chlamydial cervicitis during pregnancy with regard to efficacy, side effects, and compliance.
METHODS: In a prospective manner, 48 pregnant patients with cervical chlamydial infections diagnosed by routine screening tests were randomly assigned to receive either erythromycin, 500 mg q.i.d. for 7 days (N = 24), or azithromycin, 1 g as a one-time dose (N = 24). All sexual partners were given prescriptions for doxycycline, 100 mg b.i.d. for 7 days. The treatment efficacy was assessed by follow-up chlamydia testing 3 weeks after the therapy was completed. The side effects, intolerance to therapy, and overall compliance were evaluated by means of a standardized posttreatment questionnaire.
RESULTS: There was no significant difference in cure rates noted between the erythromycin group and the azithromycin group (77% vs. 91%, respectively; P = 0.24). Gastrointestinal side effects were reported more frequently among patients treated with erythromycin compared with patients treated with azithromycin (45% vs. 17%, respectively; P = 0.004). The patients who received erythromycin reported intolerance to therapy secondary to side effects more frequently than patients who received azithromycin (23% vs. 4%, respectively; P = 0.07). Furthermore, the patients in the azithromycin group were more likely to complete their course of therapy as prescribed than the patients in the erythromycin group (100% vs. 61%, respectively; P = 0.002).
CONCLUSIONS: Azithromycin is efficacious and well tolerated for the treatment of chlamydial cervicitis in pregnancy. Erythromycin, though efficacious, is poorly tolerated, as demonstrated by the number of patients reporting significant side effects during the course of therapy. Since the cost of azithromycin is comparable to that of generic erythromycin, the present study supports the use of azithromycin as an alternative to erythromycin for the treatment of chlamydial cervicitis in pregnancy.
A randomized, prospective trial comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy.
OBJECTIVE: Our purpose was to evaluate the efficacy of amoxicillin as an alternative therapy to erythromycin for the treatment of cervical chlamydial infections during pregnancy.
STUDY DESIGN: A randomized, prospective trial of two treatment regimens for Chlamydia trachomatis was performed in a cohort of pregnant women enrolled for care in an inner-city, university-based prenatal clinic, with an alternate-therapy crossover arm for primary treatment failures. Pregnant women diagnosed with chlamydial infection by McCoy cell culture of cervical swabs were assigned to receive either 500 mg of amoxicillin three times daily or 500 mg of erythromycin four times daily for 7 days. Patients' partners were treated with doxycycline. Compliance information was obtained by a standardized questionnaire at a posttherapy follow-up visit. Patients with positive follow-up cultures were crossed over into the alternate treatment arm and recultured at a later visit.
RESULTS: During the study period 74 women consented to participate in this trial; 36 were treated with amoxicillin and 38 with erythromycin. Initial cure rates of 82.3% (28/34) for the amoxicillin group and 84.6% (27/32) for erythromycin were obtained before crossover (p = 0.91); four patients in each group were lost to follow-up. Overall cure rates after crossover were 84.6% (33/39) for amoxicillin and 84.2% (32/38) for erythromycin (p = 0.83). In the amoxicillin group 12.8% of patients reported side effects compared with 31.6% treated with erythromycin (p = 0.09), although seven erythromycin-treated patients compared with none of those in the amoxicillin arm stopped therapy because of side effects (p = 0.02).
CONCLUSION: Amoxicillin offers a reasonable alternative to erythromycin for the treatment of Chlamydia trachomatis in pregnancy, on the basis of both cure rates and patient compliance.
A randomized, prospective trial comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy.
OBJECTIVE: Our purpose was to evaluate the efficacy of amoxicillin as an alternative therapy to erythromycin for the treatment of cervical chlamydial infections during pregnancy.
STUDY DESIGN: A randomized, prospective trial of two treatment regimens for Chlamydia trachomatis was performed in a cohort of pregnant women enrolled for care in an inner-city, university-based prenatal clinic, with an alternate-therapy crossover arm for primary treatment failures. Pregnant women diagnosed with chlamydial infection by McCoy cell culture of cervical swabs were assigned to receive either 500 mg of amoxicillin three times daily or 500 mg of erythromycin four times daily for 7 days. Patients' partners were treated with doxycycline. Compliance information was obtained by a standardized questionnaire at a posttherapy follow-up visit. Patients with positive follow-up cultures were crossed over into the alternate treatment arm and recultured at a later visit.
RESULTS: During the study period 74 women consented to participate in this trial; 36 were treated with amoxicillin and 38 with erythromycin. Initial cure rates of 82.3% (28/34) for the amoxicillin group and 84.6% (27/32) for erythromycin were obtained before crossover (p = 0.91); four patients in each group were lost to follow-up. Overall cure rates after crossover were 84.6% (33/39) for amoxicillin and 84.2% (32/38) for erythromycin (p = 0.83). In the amoxicillin group 12.8% of patients reported side effects compared with 31.6% treated with erythromycin (p = 0.09), although seven erythromycin-treated patients compared with none of those in the amoxicillin arm stopped therapy because of side effects (p = 0.02).
CONCLUSION: Amoxicillin offers a reasonable alternative to erythromycin for the treatment of Chlamydia trachomatis in pregnancy, on the basis of both cure rates and patient compliance.
Randomized prospective study comparing erythromycin, amoxicillin, and clindamycin for the treatment of chlamydia trachomatis in pregnancy.
OBJECTIVE: The purpose of this study was to compare the efficacy and side effects of erythromycin, amoxicillin, and clindamycin in eradicating Chlamydia trachomatis from the lower genital tract of pregnant women.
METHODS: A total of 174 women at <36 weeks gestation with positive cervical cultures for C. trachomatis were enrolled. Patients were assigned in a randomized prospective fashion to either erythromycin (500 mg q.i.d, for 7 days), amoxicillin (500 mg t.i.d, for 7 days), or clindamycin (600 mg t.i.d, for 10 days). Six women elected not to participate and 8 patients were lost to follow-up, leaving 53 patients in the erythromycin group, 55 patients in the amoxicillin group, and 52 patients in the clindamycin group. All sexual partners of the enrolled women were offered doxycycline (100 mg b.i.d. for 7 days) and patients were instructed to use barrier contraception until treatment was complete.
RESULTS: All 3 medications were effective agents for the treatment of antenatal C. trachomatis infection with treatment efficacies of 96%, 94%, and 98% for the erythromycin, amoxicillin, and clindamycin groups, respectively. When the antibiotic groups were compared, no statistically significant differences were noted in intolerance. However, the differences in the incidence of gastrointestinal symptoms between erythromycin and amoxicillin and/or clindamycin were significant (P < 0.05).
CONCLUSIONS: These findings suggest that 1) all 3 antibiotic regimens are efficacious, 2) erythromycin has a higher incidence of side effects, and 3) amoxicillin or clindamycin are reasonable alternatives for the treatment of C. trachomatis in pregnant patients unable to tolerate erythromycin.
Options:
A: Amoxycillin was found to be less effective than erythromycin but better tolerated.
B: Amoxycillin was found to be as effective as erythromycin and better tolerated.
C: Clindamycin and azithromycin were found to be ineffective.
D: Erythromycin was found to be the only effective antibiotic.
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B
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5
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of different antibiotic regimens for treating gonorrhoea in pregnant women in terms of microbiological cure? Please answer this question based on the information provided below:
Treatment of gonorrhea in pregnancy.
OBJECTIVE: To evaluate prospectively the 1989 Centers for Disease Control recommendations for treatment of gonorrhea in pregnancy.
METHODS: Two hundred fifty-two women referred with probable endocervical gonorrhea had pre-treatment endocervical, rectal, and oral cultures for Neisseria gonorrhoeae and direct fluorescent antibody testing for Chlamydia trachomatis. They were assigned randomly to receive ceftriaxone 250 mg intramuscularly (IM), spectinomycin 2 g IM, or amoxicillin 3 g orally plus probenecid 1 g orally. Treatment was unblinded and in a 1:1:1 distribution.
RESULTS: Two hundred forty-five women (97%) had endocervical infection, 68 (27%) had rectal infection, and 17 (7%) had pharyngeal infection. One hundred two of 252 women (40%) had concomitant endocervical C trachomatis. The overall efficacy was 235 of 252 subjects (93%) (95% confidence interval [CI] 90.1-96.4%). Ceftriaxone was effective in 80 of 84 cases (95%) (95% CI 90.6-99.9%), amoxicillin with probenecid was effective in 75 of 84 cases (89%) (95% CI 82.5-96%), and spectinomycin was effective in 80 of 84 cases (95%) (95% CI 90.6-99.9%). No significant difference was noted in overall efficacy or by site of infection. There was no increased incidence of congenital malformations in the offspring spring of any treatment group.
CONCLUSIONS: Ceftriaxone and spectinomycin are safe and effective for the treatment of gonorrhea in pregnancy. Amoxicillin with probenecid has lower efficacy and is not recommended for treatment of gonococcal infection in pregnancy.
Treatment of gonorrhea in pregnancy.
OBJECTIVE: To evaluate prospectively the 1989 Centers for Disease Control recommendations for treatment of gonorrhea in pregnancy.
METHODS: Two hundred fifty-two women referred with probable endocervical gonorrhea had pre-treatment endocervical, rectal, and oral cultures for Neisseria gonorrhoeae and direct fluorescent antibody testing for Chlamydia trachomatis. They were assigned randomly to receive ceftriaxone 250 mg intramuscularly (IM), spectinomycin 2 g IM, or amoxicillin 3 g orally plus probenecid 1 g orally. Treatment was unblinded and in a 1:1:1 distribution.
RESULTS: Two hundred forty-five women (97%) had endocervical infection, 68 (27%) had rectal infection, and 17 (7%) had pharyngeal infection. One hundred two of 252 women (40%) had concomitant endocervical C trachomatis. The overall efficacy was 235 of 252 subjects (93%) (95% confidence interval [CI] 90.1-96.4%). Ceftriaxone was effective in 80 of 84 cases (95%) (95% CI 90.6-99.9%), amoxicillin with probenecid was effective in 75 of 84 cases (89%) (95% CI 82.5-96%), and spectinomycin was effective in 80 of 84 cases (95%) (95% CI 90.6-99.9%). No significant difference was noted in overall efficacy or by site of infection. There was no increased incidence of congenital malformations in the offspring spring of any treatment group.
CONCLUSIONS: Ceftriaxone and spectinomycin are safe and effective for the treatment of gonorrhea in pregnancy. Amoxicillin with probenecid has lower efficacy and is not recommended for treatment of gonococcal infection in pregnancy.
A randomized trial that compared oral cefixime and intramuscular ceftriaxone for the treatment of gonorrhea in pregnancy.
OBJECTIVE: The purpose of this study was to evaluate prospectively the Centers for Disease Control recommendations for the treatment of gonococcal infection in pregnancy.
STUDY DESIGN: One hundred sixty-one women who were referred with probable endocervical gonorrhea underwent pretreatment endocervical, anal, and oral cultures for Neisseria gonorrhoeae. The women were randomly assigned to receive ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally. Treatment was open and in a 1:1 distribution. There were 95 evaluable patients. The tests of cure cultures were performed 4 to 10 days after treatment.
RESULTS: Eighty-six women (91%) had endocervical infection; 39 women (41%) had anal infection, and 11 women (12%) had pharyngeal infection. Fifty of 95 women (53%) had concomitant endocervical chlamydial infection. The overall efficacy was 91 of 95 subjects (95.8%; 95% CI, 89.6%-98.8%). Ceftriaxone was effective in 41 of 43 cases (95%; 95% CI, 84.2%-99.4%), and cefixime was effective in 50 of 52 cases (96%; 95% CI, 86.8%-99.5%). No significant difference was noted in the overall efficacy or by site of infection. Three of the 4 women who experienced treatment failures admitted to unprotected intercourse before their test of cure culture.
CONCLUSION: Both intramuscular ceftriaxone 125 mg and oral cefixime 400 mg appear to be effective for the treatment of gonococcal infection in pregnancy.
Options:
A: Amoxycillin with probenicid, spectinomycin, and ceftriaxone all have similar effects on microbiological cure.
B: Only amoxycillin with probenicid was found to be effective in achieving microbiological cure.
C: Spectinomycin and ceftriaxone were found to be less effective than amoxycillin with probenicid in achieving microbiological cure.
D: None of the antibiotic regimens tested were effective in achieving microbiological cure.
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A
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6
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What interventions have been found to be effective in decreasing the risk of mother-to-child transmission of HIV infection? Please answer this question based on the information provided below:
Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: pediatric AIDS Clinical Trials Group Protocol 076--results and treatment recommendations.
Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.
BACKGROUND AND METHODS: Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected.
RESULTS: From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar.
CONCLUSIONS: In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.
Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.
BACKGROUND AND METHODS: A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 (HIV-1) is transmitted from mother to infant. We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load, the risk of HIV-1 transmission, and the efficacy of zidovudine treatment. Viral cultures were obtained, and HIV-1 RNA was measured by two assays in samples of maternal blood obtained at study entry and at delivery.
RESULTS: In 402 mother-infant pairs, the rate of transmission of HIV-1 was 7.6 percent (95 percent confidence interval, 4.3 to 12.3 percent) with zidovudine treatment and 22.6 percent (95 percent confidence interval, 17.0 to 29.0 percent) with placebo (P<0.001). In the placebo group, a large viral burden at entry or delivery or a positive culture was associated with an increased risk of transmission (the transmission rate was greater than 40 percent in the highest quartile of the RNA level). In both groups, transmission occurred at a wide range of maternal plasma HIV-1 RNA levels. Zidovudine reduced plasma RNA levels somewhat (median reduction, 0.24 log). Zidovudine was effective regardless of the HIV-1 RNA level or the CD4+ count at entry. In the zidovudine group, however, after we adjusted for the base-line HIV-1 RNA level and CD4+ count, the reduction in viral RNA from base line to delivery was not significantly associated with the risk of transmission of HIV-1.
CONCLUSIONS: A high maternal plasma concentration of virus is a risk factor for the transmission of HIV-1 from an untreated mother to her infant. The reduction in such transmission after zidovudine treatment is only partly explained by the reduction in plasma levels of viral RNA. To prevent HIV-1 transmission, initiating maternal treatment with zidovudine is recommended regardless of the plasma level of HIV-1 RNA or the CD4+ count.
6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant.
BACKGROUND: Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding.
METHODS: A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat.
FINDINGS: Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group.
INTERPRETATION: A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding.
Prevention of mother-to-child transmission of HIV in Africa: uptake of pregnant women in a clinical trial in Abidjan, Côte d'Ivoire.
Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.
BACKGROUND: The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life.
METHODS: From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis.
FINDINGS: Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups.
INTERPRETATION: Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
A randomised trial of mode of delivery in women infected with the human immunodeficiency virus.
OBJECTIVE: During the pilot phase of a trial to evaluate the effectiveness of caesarean section delivery compared with vaginal delivery in reducing mother-to-child transmission of human immunodeficiency virus (HIV) infection, the feasibility of randomisation to mode of delivery was assessed.
DESIGN: At 36 weeks of pregnancy, women infected with HIV were randomly allocated to either caesarean section delivery at 38 weeks or vaginal delivery. Information was also collected on the reasons why women were not enrolled, either because they refused or had a contraindication.
SETTING: Fifty-one centres in six European countries.
POPULATION: Pregnant women with confirmed HIV-1 infection.
MAIN OUTCOME MEASURES: Randomisation.
RESULTS: Three-hundred and thirty-nine women had been randomised by the end of 1996, the large majority from Italy (n = 250) and France (n = 54), with 22 from South Africa, three from Sweden, nine from Barcelona and one from London. A further 150 women were eligible but had not been randomised. Forty-eight women (14%) were not delivered according to the arm to which they were randomised; the majority (n = 44) were changed from vaginal to caesarean section delivery. There is wide variation between European countries in the acceptability and adherence to the mode of delivery trial.
CONCLUSION: The pilot phase of this trial has shown that in some settings randomisation to mode of delivery is feasible and acceptable, but that in other settings clinicians and pregnant women are more reluctant to be randomised. Pending further information on transmission rates and accrual, enrollment into the trial continues.
Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial.
BACKGROUND: Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.
METHODS: Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.
FINDINGS: We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1.8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10.5%) of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few postpartum complications and no serious adverse events in either group.
INTERPRETATION: Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother.
Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.
BACKGROUND: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour.
METHODS: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR.
FINDINGS: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery.
INTERPRETATION: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.
Administration of zidovudine during late pregnancy and delivery to prevent perinatal HIV transmission--Thailand, 1996-1998.
Worldwide, approximately 500,000 infants are perinatally infected with human immunodeficiency virus (HIV) each year, most of whom are born in developing countries. In 1994, a clinical trial in the United States and France demonstrated that zidovudine (ZDV) administered orally five times a day to HIV-infected pregnant women starting at 14-34 weeks' gestation, intravenously during labor, and orally to their newborns for 6 weeks reduced the risk for perinatal HIV transmission by two thirds. In 1994, this regimen was recommended as standard care in the United States; however, because of its complexity and cost, this regimen has not been implemented in most developing countries, and no other intervention had been efficacious in reducing perinatal HIV transmission. In 1996, the Ministry of Public Health of Thailand and Mahidol University, in collaboration with CDC, initiated a randomized, placebo-controlled trial of a simpler and less expensive regimen of ZDV to prevent perinatal HIV transmission. This report describes preliminary trial results, which indicate that a short-term antenatal regimen of ZDV reduced the risk for perinatal HIV transmission by approximately half.
Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group.
The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus (HIV) intravenous immunoglobulin (HIVIG) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized, intravenous immunoglobulin (IVIG)-controlled trial of HIVIG maternal-infant HIV transmission prophylaxis. Using 200 mg/kg, mean half-life and volume of distribution (Vd) in women were 15 days and 72 mL/kg, respectively, after one and 32 days and 154 mL/kg after three monthly infusions, with stable 4 mL/kg/day clearance. Transplacental passage occurred. Newborn single-dose half-life, Vd, and clearance were 30 days, 143 mL/kg, and 4 mL/kg/day, respectively. HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen, and plasma HIV-1 RNA levels were stable. Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions. No adverse hematologic, blood chemistry, or immunologic effects were seen. HIVIG is well-tolerated in HIV-infected pregnant women and their newborns, clears antigenemia, crosses the placenta, and exhibits pharmacokinetics similar to those of other immunoglobulin preparations.
Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.
Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts </=500/microL (22% had counts <200/microL) and required zidovudine for maternal health (24% received zidovudine before pregnancy). Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P=.005; 10.0% vs. 3.6% transmission for count <200 vs. >/=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.
Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial.
BACKGROUND: In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire.
METHODS: From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population.
FINDINGS: 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months.
INTERPRETATION: Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.
Options:
A: Zidovudine, nevirapine, and elective caesarean section
B: Zidovudine, hyperimmune immunoglobulin, and vaginal delivery
C: Nevirapine, non-specific immunoglobulin, and vaginal delivery
D: Elective caesarean section, non-specific immunoglobulin, and short course therapy
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A
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7
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of calcium and sodium chloride in reducing leg cramps during pregnancy? Please answer this question based on the information provided below:
The effect of oral magnesium substitution on pregnancy-induced leg cramps.
OBJECTIVE: Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation.
STUDY DESIGN: Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed.
RESULTS: Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002).
CONCLUSION: Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps.
Calcium treatment of leg cramps in pregnancy. Effect on clinical symptoms and total serum and ionized serum calcium concentrations.
Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation.
Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps.
60 pregnant women underwent a double blind trial with calcium or ascorbic acid (1 g twice daily) as treatment for leg cramps. There was no significant difference between the two treatment groups with respect to clinical improvement. In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment (irrespective of drug used). In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy. Serum total and ionized calcium concentrations, serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups. No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms. Serum magnesium concentrations were at or just below the lower normal limit (for non pregnant women) in treated women and pregnant controls.
Cramps in pregnancy.
Effects of a multivitamin mineral supplement on zinc and copper status during pregnancy.
The effect of a multivitamin-mineral supplement was investigated during pregnancy according to a double-blind protocol by determining zinc and copper in maternal plasma, mononuclear and polynuclear zinc and copper at the third, sixth, eighth, and ninth months of gestation. The subjects were supplemented from the first trimester until delivery. A significant decrease was observed in plasma zinc that varied from 11.5 mumol/L to 10.8 mumol/L in the supplemented group (n = 29) and from 11 mumol/L to 10 mumol/L in the placebo group (n = 33) at 3 and 9 mo of gestation, respectively. In contrast, plasma copper levels increased in a way depending upon the stage of gestation in both groups: from 24.7 to 28.2 mumol/L in the treated group and from 24.9 to 30.9 mumol/L in the placebo group at 3 and 9 mo of gestation, respectively, but the difference was only significant in the placebo group. No difference between groups was observed in mononuclear and polynuclear zinc or copper levels. These trace elements were also determined in cord blood at delivery. There were no statistically significant differences in zinc and copper concentration found in placebo group and supplemented group. Finally, the beneficial effect of supplementation on muscular cramps and appearance of vergetures was noted.
Options:
A: Calcium was found to be ineffective, while sodium chloride significantly reduced leg cramps.
B: Both calcium and sodium chloride were found to reduce leg cramps, but the results for sodium chloride may be outdated due to dietary changes.
C: Calcium significantly reduced leg cramps, but sodium chloride had no effect.
D: Neither calcium nor sodium chloride had any significant effect on reducing leg cramps.
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B
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8
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effect of maternal hydration on amniotic fluid volume in pregnant women with oligohydramnios or normal amniotic fluid volume? Please answer this question based on the information provided below:
Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods.
OBJECTIVE: To determine the effect of maternal hydration with intravenous (i.v.) isotonic fluid, i.v. hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios.
METHODS: Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h i.v. isotonic fluid, 2 L/2 h i.v. hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration.
RESULTS: Eighty-four patients (n=21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the i.v. hypotonic and oral water groups (2.8+/-1.9, P < .001; 3.8 +/-1.9, P < .001, respectively), but not in the i.v. isotonic group (0.5+/-1.1), compared with the control group (0.5+/-1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after i.v. isotonic hydration (32.0+/-2.9 to 29.5+/-2.3, P < .001; 11.0+/-1.6 to 10.1+/-1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the i.v. hypotonic group (r=.58, P < .001) and oral water group (r =.63, P < .001).
CONCLUSION: Maternal hydration with either i.v. hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration.
Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods.
OBJECTIVE: To determine the effect of maternal hydration with intravenous (i.v.) isotonic fluid, i.v. hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios.
METHODS: Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h i.v. isotonic fluid, 2 L/2 h i.v. hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration.
RESULTS: Eighty-four patients (n=21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the i.v. hypotonic and oral water groups (2.8+/-1.9, P < .001; 3.8 +/-1.9, P < .001, respectively), but not in the i.v. isotonic group (0.5+/-1.1), compared with the control group (0.5+/-1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after i.v. isotonic hydration (32.0+/-2.9 to 29.5+/-2.3, P < .001; 11.0+/-1.6 to 10.1+/-1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the i.v. hypotonic group (r=.58, P < .001) and oral water group (r =.63, P < .001).
CONCLUSION: Maternal hydration with either i.v. hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration.
Maternal hydration increases amniotic fluid index.
Although adequate amniotic fluid (AF) volume is considered an important aspect of fetal well-being, the etiology of decreased AF volume is not well understood. A randomized blinded trial was designed to examine our hypothesis that maternal hydration would increase the AF index in women with low AF indexes. Women seen in our testing centers were randomized into control or hydration groups. The control group was instructed to drink their normal amount of fluid; the hydration group was instructed to drink 2 L of water, in addition to their usual amount of fluid, 2-4 hours before the post-treatment AF index. The women returned for the post-treatment AF index the same or following day. The mean post-treatment AF index was significantly greater in the hydration group (6.3 versus 5.1; P less than .01), as was the mean change in AF index (post-treatment AF index--pre-treatment AF index: 1.5 versus 0.31; P less than .01). These findings suggest that maternal oral hydration increases AF volume in women with decreased fluid levels.
Maternal hydration increases amniotic fluid index.
Although adequate amniotic fluid (AF) volume is considered an important aspect of fetal well-being, the etiology of decreased AF volume is not well understood. A randomized blinded trial was designed to examine our hypothesis that maternal hydration would increase the AF index in women with low AF indexes. Women seen in our testing centers were randomized into control or hydration groups. The control group was instructed to drink their normal amount of fluid; the hydration group was instructed to drink 2 L of water, in addition to their usual amount of fluid, 2-4 hours before the post-treatment AF index. The women returned for the post-treatment AF index the same or following day. The mean post-treatment AF index was significantly greater in the hydration group (6.3 versus 5.1; P less than .01), as was the mean change in AF index (post-treatment AF index--pre-treatment AF index: 1.5 versus 0.31; P less than .01). These findings suggest that maternal oral hydration increases AF volume in women with decreased fluid levels.
Maternal hydration increases amniotic fluid index in women with normal amniotic fluid.
OBJECTIVE: To test the hypothesis that maternal oral hydration would increase the amniotic fluid (AF) index in pregnancies with normal AF.
METHODS: Forty women with a normal AF index (7.0-24.0 cm) were randomized to either the control or hydration group. Women in the hydration group drank 2 L of water and returned for the post-treatment AF index in 4-6 hours, whereas women in the control group drank only 100 mL of water during the same time period. The investigator performing the AF index was blinded to the subject's group. The pre- and post-treatment AF indexes and maternal urine specific gravities were compared between the groups.
RESULTS: The mean AF index in the hydration group increased significantly by 3.0 +/- 2.4 cm (P < or = .0001) whereas it declined significantly by 1.5 +/- 2.7 cm in the control group (P < or = .02). The maternal urine specific gravities also changed significantly in the expected direction, with those in the hydration group decreasing and those in the control group increasing (P < or = .0001). There was a regression coefficient of -0.6 (P < or = .0001) between the change in urine specific gravity and the change in AF index. The mean time between the pre- and post-treatment AF indexes was not different between the groups.
CONCLUSIONS: Maternal oral hydration increased the AF index by approximately 16%, whereas fluid restriction decreased the AF index by 8% in women with normal AF. These findings support previous data that maternal hydration increased the AF index by 31% in women with decreased AF and suggest that maternal fluid volume or osmolality may have a role in maintaining the AF volume.
A randomized clinical trial comparing the effect of maternal intravenous hydration and placebo on the amniotic fluid index in oligohydramnios.
OBJECTIVE: To compare the treatment of acute intravenous hydration with placebo in term pregnant women manifesting oligohydramnios.
METHODS: All patients with oligohydramnios who met the inclusion criteria were offered participation in this randomized, double-blind, placebo-controlled study. After ruling out rupture of membranes and maternal and fetal complications, we recruited 44 women with third trimester singleton pregnancies having an amniotic fluid index (AFI) of less than 6. Patients were randomized into treatment or control groups. Patients in the treatment group received a continuous intravenous infusion of (1/2) normal saline (NS) at a rate of 1000 mL/h for two hours. Patients in the placebo group received an intravenous infusion of (1/2) NS at 10 mL/h for two hours. The AFI was re-assessed by the same sonographer one hour after the hydration was completed. Both the patient and the examiner were blinded to the study groups.
RESULTS: Maternal age, parity, gestational age, and birth weight were not significantly different between the two groups. The AFI increased significantly in both treatment (3.8 +/- 1.2 vs. 5.3 +/- 2.5, p < 0.05) and placebo (4 +/- 1.3 vs. 5.5 +/- 2.4, p < 0.05) groups. Moreover, the changes in AFI did not significantly differ between the treatment and the placebo groups (1.2 +/- 2.1 vs. 1.5 +/- 2.1, respectively; p > 0.05).
CONCLUSIONS: There are statistically significant short-term increases in the AFI in patients with oligohydramnios whether the patients are treated with intravenous fluids or not. The short-term increase in AFI may reflect physiologic diurnal variations in the amniotic fluid.
Options:
A: Maternal hydration has no effect on amniotic fluid volume.
B: Maternal hydration decreases amniotic fluid volume.
C: Maternal hydration increases amniotic fluid volume.
D: Maternal hydration only affects amniotic fluid volume in women with normal amniotic fluid volume.
|
C
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9
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of maternal oxygen therapy for suspected impaired fetal growth on fetal growth and perinatal outcome? Please answer this question based on the information provided below:
Maternal hyperoxygenation in the treatment of intrauterine growth retardation.
OBJECTIVE: In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated.
STUDY DESIGN: Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery.
RESULTS: Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively.
CONCLUSION: Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.
A prospective randomised comparison of the effect of continuous O2 therapy and bedrest on fetuses with absent end-diastolic flow on umbilical artery Doppler waveform analysis.
A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.
OBJECTIVE: To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.
DESIGN: A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.
SETTING: A tertiary referral hospital in South Africa.
PARTICIPANTS: Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.
METHODS: After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.
MAIN OUTCOME MEASURES: Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.
RESULTS: There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).
CONCLUSION: This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.
A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.
OBJECTIVE: To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.
DESIGN: A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.
SETTING: A tertiary referral hospital in South Africa.
PARTICIPANTS: Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.
METHODS: After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.
MAIN OUTCOME MEASURES: Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.
RESULTS: There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).
CONCLUSION: This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.
A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.
OBJECTIVE: To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.
DESIGN: A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.
SETTING: A tertiary referral hospital in South Africa.
PARTICIPANTS: Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.
METHODS: After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.
MAIN OUTCOME MEASURES: Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.
RESULTS: There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).
CONCLUSION: This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.
Options:
A: Maternal oxygen therapy significantly improved fetal growth and reduced perinatal mortality.
B: Maternal oxygen therapy was associated with a lower perinatal mortality rate, but the evidence is insufficient to evaluate its overall benefits and risks.
C: Maternal oxygen therapy had no effect on fetal growth or perinatal mortality.
D: Maternal oxygen therapy increased the risk of adverse perinatal outcomes.
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B
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10
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the effectiveness of maternal nutrient supplementation for suspected impaired fetal growth on fetal growth and perinatal outcomes? Please answer this question based on the information provided below:
[Maternal blood and amniotic fluid insulin-like growth factor detection and amniotic cavity drug delivery for early diagnosis and management of fetal growth restriction].
OBJECTIVE: To explore the relationship between insulin-like growth factors (IGFs) and fetal growth restriction (FGR) and early treatment of FGR.
METHODS: The levels of IGF-I and IGF-II were detected with radioimmunoassay in maternal blood and amniotic fluid samples of 44 pregnant women with FGR and 36 normal gravidas. The 44 gravidas with FGR were randomized into treatment group with amino acid by a pediatric administration to the amniotic cavity formula and control group with intravenous infusion of compound amino acid. The therapeutic effects were compared between the two groups on the basis of B-type ultrasound findings.
RESULTS: Maternal blood IGF-I and amniotic fluid IGF-I and IGF-II levels in the pregnant women with FGR were significantly lower than those in normal gravidas (P<0.01). After therapy, IGF-I and IGF-II levels were significantly increased in the treatment group (P<0.01), but no obvious changes in IGF-I and IGF-II levels were observed in the control group (P>0.05). Compared with the control group, IGF-I and IGF-II levels increased significantly in the amniotic fluid in the treatment group, with also marked elevation of IGF-I levels in maternal blood (P<0.01). Better therapeutic effects were achieved in the treatment group than in the control group (P<0.01), and the birth weights of the neonates in the treatment group were basically normal.
CONCLUSIONS: Detection of amniotic fluid IGF-I and IGF-II and maternal blood IGF-I can help predict the condition and facilitate early diagnosis of FGR. Injection of pediatric amino acid into the amniotic cavity can be effective for treatment of FGR.
[Carnitine in therapy of placental insufficiency--initial experiences].
Carnitine (3-hydroxy and 4-trimethylaminobutyrate) present in all living cells, plays an important role in the oxidation of fatty acids. It is known that high dose carnitine activates surfactant synthesis. Given to women with imminent premature delivery, its benefit on the post natal period is proved. Own studies showed an increased need of carnitine during pregnancy. Therefore the questions rose if carnitine substitution improves placental insufficiency. 15 pregnant women were treated with 2 x 1 g carnitine orally for one week and with 1 x 1 g carnitine during the following 7 days when their fetus showed a retardation of 1-3 weeks. The control group were 15 untreated patients with the same problems of retardation. The placental insufficiency was diagnosed by fetometry, by blood parameters and the doppler ultrasound flow measurement. In the group of the treated patients 11 out of 15 showed an improvement, in 4 patients no effect of carnitine was seen and in 1 patient the retardation increased. In the control group 8 out of 15 patients showed a spontaneous improvement of fetal growth, 2 women did not have a change in their retardation and 5 patients had to be hospitalized because of increasing placental insufficiency. Inspite of the small number of patients a tendency towards a profit in carnitine treatment for placental insufficiency seems to be real.
[Effect of the protein-free calf-blood-extract (Solcoseryl) on the excretion of estrogens in chronic placental insufficiency].
In a double blind study the action of Solcoseryl was tested in 31 patients during late pregnancy with chronic placental insufficiency. Under treatment with Solcoseryl a significant increase in urinary estrogen excretion occurred in relation to the placebo-group.
[Therapeutic efforts and prenatal modification of selected disordered fetomaternal relations].
Based on the current view about disturbances of the feto-materno-placental unit we examined 37 women with suspected intrauterine fetal growth retardation and 12 women with threatened premature labor and looked for possibilities of antenatal therapeutic influence of nutritive, respiratory, endocrine and hemodynamic insufficiency. In a randomized study we can prove a normal increase of the distance between symphysis pubis and fundus as well, as the biparietal diameter not only following bedrest but also following bedrest with additional intravenous infusion of glucose respectively oral application of galactose. The high rate of hypotrophic babies is no argument against a positive influence on nutritive insufficiency, but the acquired retardation can not be compensated totally. Neither a positive influence on the endocrine insufficiency nor the moderate respiratory one could be found. As well by maternal transcutaneous nerval stimulation as by maternal oxygen inhalation an oral long-term tocolysis we can demonstrate a considerable improvement of the uteroplacental perfusion measured with isotopes. These positive aspects are basis for further investigations. An important supposition to a successful therapy remains an early diagnosis.
[Therapy of suspected intrauterine fetal retardation].
In a randomized prospective study, performed on 45 pregnancies with clinical and sonographic suspicion for intrauterine fetal growth retardation, examinations were done to evaluate the therapeutic effect of bed rest and of additional daily administered glucose infusions or oral galactose applications respectively on the fetal growth, the hemodynamic, respiratory and endocrine insufficiency of the materno-feto-placental unit as well as selected biochemical parameters of the umbilical blood. There is no positive therapeutic effect, either on the impaired endocrine partial function nor on the reduced respiratory function of the feto-placental unit. It is obvious, that despite the improvement of the nutritional supply of the fetus and the revival of the regular fetal growth, the previous lack of fetal growth can not be altered. This can be demonstrated in all three therapeutic groups due to the fact of a resulting high hypotrophy-rate of the newborns. The results prove that the additional supply of the fetus with glucose or galactose does not remarkably improve the therapeutic effectivity as opposed by strict bed rest alone.
Options:
A: Nutrient supplementation significantly improved fetal growth and reduced the number of small for gestational age infants.
B: Nutrient supplementation had no significant effect on fetal growth or the number of small for gestational age infants.
C: Nutrient supplementation significantly increased the number of small for gestational age infants.
D: Nutrient supplementation had significant adverse effects on maternal health.
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B
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11
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the most effective treatment for symptomatic vaginal candidiasis in pregnancy, and what is the recommended duration of treatment? Please answer this question based on the information provided below:
Comparative evaluation of Monistat and Mycostatin in the treatment of vulvovaginal candidiasis.
Double-blind investigation of R-42470 (terconazole cream 0.4%) and clotrimazole (cream 1%) for the topical treatment of mycotic vaginitis.
A total of 78 patients took part in a double-blind randomized comparison of the efficacy, acceptability and tolerance of a new antifungal terconazole (R-42470) (cream 0.4%) with the well established and clinically effective clotrimazole (cream 1%) for the topical treatment of mycotic vaginitis. Five grams of cream were applied to the vagina for 7 consecutive days. Twenty non-pregnant and 19 pregnant patients were included in each group. Clinical and mycological controls were carried out one week and one month after completion of therapy and 89.7% of the patients treated with terconazole responded to therapy and 82.1% patients treated with clotrimazole were cured. Statistical analysis showed no significant difference when the results of the terconazole treated patients and the clotrimazole group were compared.
Candida albicans vaginitis: the problem is diagnosis, the enigma is treatment.
At the UCLA Vulvovaginitis Clinic, 63 patients were diagnosed as having symptomatic Candida albicans vaginal infections. In a random select manner 3-day treatment with 200-mg clotrimazole suppositories was compared with 7-day treatment using 100-mg clotrimazole suppositories. 7- and 35-day follow-up of all patients entered revealed no statistical difference between the two groups, suggesting that short-term treatment is most efficacious and can be expected to work better since patient compliance is primarily a function of duration of treatment. In 50 cases of C. albicans patients treated with miconazole or clotrimazole in a random manner, the recurrence rate was 8 or 16. All patients in the study received perianal cultures for C. albicans before treatment and 7 and 35 days after treatment. 5 of the 8 patients with recurrence had perianal positive cultures at the 7- and 35-day check suggesting this as a source of recurrence. It is suggested that patients with persistently high perianal cultures after treatment be given an oral fungicide or fungistat to lower chronic recurrent C. albicans.
Treatment of vulvovaginal candidiasis in pregnancy. A comparative study.
A carefully controlled comparative study showed miconazole nitrate 2% vaginal cream (Monistat) to be a highly effective agent in the treatment of vaginal candidiasis in pregnant subjects. Miconazole nitrate was significantly more effective than nystatin (Mycostatin) in the treatment of vaginal candidiasis in all three trimesters of pregnancy, and also more effective regardless of whether the candidal infection was primary or recurrent. Observations relating to the safety of this therapy during pregnancy were made and discussed.
Comparison of nystatin ('Nystan') and hydrargaphen ('Penotrane') in the treatment of vaginal candidosis in pregnancy.
A dose-response study with Monistat cream.
A randomized multiregimen clinical study was undertaken using Monistat Cream for the treatment of vulvovaginal candidiasis. The objective of the study was to find if there is a shorter regimen comparable in effectiveness to the currently marketed 14-day regimen. The results indicate that there is no significant difference between the cure rate obtained for 7 days of therapy and for 14 days of therapy.
Monistat cream (miconazole nitrate) a new agent for the treatment of vulvovaginal candidiasis.
Monistat Cream (miconazole nitrate 2%), a new fungicidal agent indicated for the treatment of vulvovaginal candidiasis, was evaluated in a comparative study with nystatin vaginal tablets (100,-000 units each). A total of 95 pregnant and non-pregnant patients were treated. Miconazole nitrate was administered once daily, at bedtime, for 14 days to 55 pregnant and non-pregnant patients. Overall, 74.5% (41 of 55 patients) were cured with one course of therapy. In contrast, of 40 nystatin-treated patients (both pregnant and non-pregnant) treated twice daily for 15 days, 22 patients (57.8%) were cured with one course of therapy. This difference in cure rates was statistically significant. Side effects were minimal and comparable in the two treatment groups. No recorded instances of birth defects were observed in infants born to mothers in either treatment group. Monistate Cream, in this study, was found to be a safe and effective drug in treating both pregnant and nonpregnant patients with confirmed candidiasis.
Efficacy of econazole in the treatment of candidiasis and other vaginal discharges.
Three hundred and thirty Black pregnant patients attending the Baragwanath Hospital antenatal clinic were treated for symptomatic vaginal discharge with econazole (Ecostatin; Squibb). Patients with positive Candida albicans cultures were treated for either 7 or 14 days. The results of treatment in both groups are presented.
Prophylactic clotrimazole treatment to prevent mycoses contamination of the newborn.
A comparative trial of six day therapy with clotrimazole and nystatin in pregnant patients with vaginal candidiasis.
Options:
A: Nystatin for 14 days
B: Hydrargaphen for 7 days
C: Imidazole for 7 days
D: Clotrimazole for 3 days
|
C
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12
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of active chest physiotherapy for babies being extubated from mechanical ventilation for neonatal respiratory failure? Please answer this question based on the information provided below:
Chest physiotherapy and post-extubation atelectasis in infants.
We investigated the role of chest physiotherapy (CPT) in preventing post-extubation atelectasis (PEA) in infants. Sixty-three infants who were admitted to the neonatal intensive care unit and intubated for more than 24 hours and who showed no evidence of atelectasis by chest x-ray prior to extubation were enrolled in the study. Infants were randomly assigned to 2-hourly CPT, 4-hourly CPT, or a no CPT group. Chest physiotherapy began immediately after extubation and consisted of postural drainage, bilateral chest vibration, and suctioning. A second chest x-ray was obtained on all infants 24 hours following extubation. The three groups were comparable in birth weight, gestational age, and duration of intubation. In the 24-hour period following extubation, the incidence of PEA was not statistically significant in the three groups (P = 0.33). Two infants in the 2-hourly CPT group were placed on nasal continuous positive airway pressure; two in each of the 2-hourly and the no CPT groups required re-intubation and intermittent positive pressure ventilation to treat symptomatic atelectasis. We conclude that post extubation chest physiotherapy as used in this study did not prevent atelectasis in extubated infants.
Routine neonatal postextubation chest physiotherapy: a randomized controlled trial.
OBJECTIVE: To test the effects of a neonatal postextubation programme on the incidence of postextubation collapse and adverse outcomes.
METHODS: A randomized controlled trial was carried out at the Mater Mothers' Hospital, Brisbane. Mechanically ventilated infants were randomized into one of two groups, physiotherapy group--which involved a regimen of chest wall percussion and oropharyngeal suctioning and control group - which involved suctioning without the percussion unless indicated. Chest X-rays were taken at 6 h and at 24 h postextubation. The primary outcome measure was postextubation collapse as determined by a paediatric radiologist blinded to the group allocation.
RESULTS: One hundred and seventy-seven neonates were enrolled in the trial between 1997 and 1999. After an interim analysis, the trial was stopped early. No statistically significant difference was shown in the rate of postextubation collapse (15 of 87 (17.2%) physiotherapy group and 17 of 86 (19.8%) control group (P = 0.85)). No differences were shown between the groups in the number of apnoeic or bradycardic events, duration of requirement for supplemental oxygen or the need for re-intubation within 24 h postextubation.
CONCLUSION: The results of this trial suggest that a routine neonatal postextubation chest physiotherapy programme for all infants is not indicated. There was no evidence that chest physiotherapy is associated with any adverse outcomes.
Postextubation atelectasis: a retrospective review and a prospective controlled study.
To determine the role of chest physiotherapy in the prevention of postextubation atelectasis in neonates intubated for greater than 24 hours, a retrospective survey compared the incidence of this complication in a newborn intensive care unit prior to and following the institution of a routine of chest physiotherapy. Eight of 23 infants extubated developed atelectasis in the "pre-physio" period, whereas only one collapse occurred in 20 infants treated with a routine of physiotherapy at extubation (P less than 0.025). Subsequently a prospective controlled trial compared the use of a routine of physiotherapy at extubation with no physiotherapy. Eight of 21 infants not receiving physiotherapy developed postextubation atelectasis and none of 21 infants receiving physiotherapy developed atelectasis (P less than 0.01). Seventy-six percent of the collapses involved the right upper lobe. A vigorous program of chest physiotherapy, including postural drainage emphasizing the positions of the right upper lobe and chest vibrations, will significantly reduce the incidence of postextubation atelectasis.
Options:
A: Active chest physiotherapy significantly reduced the rate of postextubation lobar collapse and reintubation.
B: Active chest physiotherapy showed no clear benefit in reducing postextubation lobar collapse but reduced the use of reintubation.
C: Active chest physiotherapy increased the rate of postextubation lobar collapse and had no effect on reintubation.
D: Active chest physiotherapy had no effect on postextubation lobar collapse or reintubation.
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B
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13
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What are the effects of administering intravenous dexamethasone prior to extubation in newborn infants who have undergone intermittent positive pressure ventilation (IPPV)? Please answer this question based on the information provided below:
Effects of dexamethasone on pulmonary function following extubation.
Dexamethasone is often given to intubated neonates to facilitate successful extubation. To study the effects of dexamethasone on pulmonary function immediately following extubation, we conducted a randomized, blinded, placebo-controlled trial in 51 infants. All infants had been intubated for a minimum of 3 days but no more than 30 days. Mean weight at extubation was 2.41 kg in treated infants, 2.25 kg in control infants. When infants were deemed ready for extubation, dexamethasone 0.5 mg/kg/dose or an equal volume of normal saline was given in three doses 8 hours apart. The final dose was given 1 hour before extubation. Esophageal pressure, air flow integrated to tidal volume (Vt), respiratory rate, and heart rate were measured before extubation, immediately following extubation, and every 20 minutes for 80 minutes. Total pulmonary resistance (RTP), dynamic lung compliance (CL), and minute ventilation (VE) were calculated. Forty-two infants completed the study; 19 infants received dexamethasone and 23 received placebo. There was no difference between the two groups in gestational age, weight at study, or length of intubation. Vt, RTP, VE, and CL were not significantly different between the two groups over time; however, RTP increased over time in the placebo group. Heart rate was significantly lower in the dexamethasone group. We conclude that dexamethasone appears to have limited effect on pulmonary function immediately following extubation in the population studied. Further studies should evaluate the drug effect beginning at least 1 hour after extubation.
Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema.
We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.
Routine use of dexamethasone for the prevention of postextubation respiratory distress.
We evaluated the routine use of dexamethasone for the prevention of postextubation respiratory distress by entering 60 ventilated infants into a prospective, randomized, blinded study. Thirty minutes before extubation, 30 infants were given a single dose of intravenous dexamethasone (0.25 mg/kg), and 30 infants received saline placebo. Infants were intubated orotracheally for at least 48 hours following a single intubation and were maintained on low ventilator settings (F10(2) less than 0.35, intermittent mandatory ventilation [IMV] less than 6, positive end-expiratory pressure [PEEP] less than 4) at least 12 hours before extubation. Following extubation, all infants weighing less than 1500 g were routinely placed on nasal continuous positive airway pressure (NCPAP). There was no difference between the two groups in postextubation Downes' score, serum pH, PCO2, or oxygen requirement at 30 minutes, 6 hours, and 24 hours. Respiratory acidosis occurred in one steroid-treated patient and in two placebo-treated infants. Stridor occurred in four infants in each group. No infant developed postextubation lobar atelectasis or required reintubation. We conclude that prophylactic administration of dexamethasone does not improve the immediate postextubation course of infants following a single intubation and that its routine use at the time of extubation is not indicated.
Options:
A: It significantly reduces the need for reintubation and has no side effects.
B: It significantly reduces the need for reintubation, but may cause higher blood sugar levels and glycosuria.
C: It has no significant effect on the need for reintubation and causes no side effects.
D: It increases the need for reintubation and causes higher blood sugar levels and glycosuria.
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B
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14
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the primary objective of the review comparing elective high frequency jet ventilation (HFJV) to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS)? Please answer this question based on the information provided below:
Early randomized intervention with high-frequency jet ventilation in respiratory distress syndrome.
To determine whether early use of high-frequency jet ventilation reduces neonatal mortality or pulmonary morbidity rates, we randomly selected 42 infants with clinical and radiographic evidence of severe respiratory distress syndrome to receive either high-frequency jet ventilation or conventional ventilation. Separate sequential analyses (two-sided, alpha = 0.05, power = 0.95 to detect 85:15 advantage) were performed for mortality rates, air leaks, bronchopulmonary dysplasia, intraventricular hemorrhage, and assignment crossover, and a combined analysis was performed, with death overriding other outcome variables. Enrollment was completed when the combined analysis reached the sequential design boundary indicating no treatment difference. Mortality rates (19% among infants receiving high-frequency jet ventilation vs 24% among infants receiving conventional ventilation), the incidence of air leaks (48% vs 52%), bronchopulmonary dysplasia (39% vs 41%), and intraventricular hemorrhage (33% vs 43%), and assignment crossovers (14% vs 24%) did not differs significantly between the treatment groups. We conclude that early use of high-frequency jet ventilation does not prevent or substantially reduce mortality or morbidity rates associated with assisted ventilation.
Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome.
OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome.
DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol.
SETTING: Eight tertiary neonatal intensive care units.
PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications.
RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants.
CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.
High-frequency jet ventilation in the early management of respiratory distress syndrome is associated with a greater risk for adverse outcomes.
OBJECTIVE: The objective of this investigation was to determine if high-frequency jet ventilation (HFJV) used early in the treatment of premature infants with respiratory distress syndrome was effective in reducing pulmonary morbidity without increasing the occurrence of adverse neurologic outcomes.
STUDY DESIGN: A total of 73 premature infants who met the inclusion criteria (gestational age of less than 33 weeks, birth weight of more than 500 g, age of less than 24 hours, need for assisted ventilation with peak inspiratory pressure of more than 16 and FIO2 more than 0.30, and roentgenographic evidence of respiratory distress syndrome) were randomized to either conventional (n = 36) or to high-frequency jet (n = 37) ventilation. Our goals were to maintain the infants on the assigned ventilator for at least 7 days unless they could either be extubated or meet crossover criteria. Univariate analyses were initially used to compare the two groups. Stepwise logistic regression was subsequently used to assess whether various factors independently influenced adverse outcomes.
RESULTS: The two groups of infants were similar in all obstetrical, perinatal, and neonatal demographic characteristics. The mean birth weight and gestational age in the conventional group were 930 g and 26.6 weeks and in the HFJV group, 961 g and 26.9 weeks. The infants were randomized at similar ages (7.1 and 7.3 hours of life, respectively). Their prerandomization ventilator settings and arterial blood gases were nearly identical. There were no differences in pulmonary outcomes (occurrence of air leaks, need for oxygen or ventilation at 36 weeks postconception), and there were no differences in the mean number of days oxygen was required, number of days ventilated, or length of hospital stay. Infants ventilated with HFJV were significantly more likely to develop cystic periventricular leukomalacia (10 vs 2, P = .022) or to have a poor outcome (grade IV hemorrhage, cystic periventricular leukomalacia, or death) (17 vs 7, P = .016). Logistic regression analysis revealed HFJV to be a significant independent predictor of both cystic periventricular leukomalacia and a poor outcome. The presence of hypocarbia was not an independently significant predictor of adverse outcomes.
CONCLUSIONS: With the HFJV treatment strategy that we used, use of the high-frequency jet ventilator in the early management of premature infants with respiratory distress syndrome resulted in significantly more adverse outcomes than in those treated with conventional mechanical ventilation.
Options:
A: To determine if HFJV decreases the incidence of chronic lung disease (CLD) without adverse effects.
B: To evaluate the cost-effectiveness of HFJV compared to CV.
C: To assess the long-term neurodevelopmental outcomes of infants treated with HFJV.
D: To compare the incidence of neonatal mortality between HFJV and CV.
|
A
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15
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
In preterm infants at risk for apnea, what is the effect of prophylactic use of kinesthetic stimulation on the incidence of apnea, bradycardia, and the need for intermittent positive pressure ventilation (IPPV)? Please answer this question based on the information provided below:
A controlled trial of a regularly cycled oscillating waterbed and a non-oscillating waterbed in the prevention of apnoea in the preterm infant.
Fourteen preterm infants spent a mean of 23 hours divided into 4-hour periods with and without regular oscillations, 10 infants also being studied for control periods, before and afterwards. Electrocardiogram and impedance pneumogram were recorded continuously and analysed blindly. The waterbed, with or without oscillations, had no effect on apnoea or bradycardia when compared with control periods. Infants had appreciably more episodes of severe bradycardia while on the oscillating than on the non-oscillating waterbed.
Effects of waterbed flotation on premature infants: A pilot study.
Two types of waterbeds were developed to impart compensatory vestibular-proprioceptive stimulation to premature infants. Twenty-one infants ranging in gestational age from 27 to 34 weeks and birthweights from 1,050 to 1,920 gm were included in this pilot study. Assignment to experimental and control groups was made by random design. The experimental group consisted of ten infants who were placed on a gently oscillating waterbed before the sixth postnatal day, where they remained for seven days. Their clinical progress was compared with that of a control group of 11 similar babies. Waterbed flotation was found to be a safe procedure; there was no significant effects on the infants' vital signs, weight, or frequency of emesis. Highly significant differences were found in the incidence of apnea between the two groups, with infants on the oscillating waterbed having significantly fewer apneic spells. Infants placed on the waterbed during the first four postnatal days benefited more than those placed later. A non-oscillating waterbed was found clinically useful for very small prematures with severe skin problems, for infants recovering from abdominal surgery, and for infants receiving parenteral nutrition.
Randomized clinical trial of an oscillating air mattress in preterm infants: effect on apnea, growth, and development.
To investigate claims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development, we performed a randomized clinical trial using a predetermined sample size. Preterm infants weighing from 750 to 1750 gm at birth were randomly assigned, by 250 gm strata, to either a conventional mattress (n = 63) or to an air mattress (n = 59) oscillating at 14 to 16 regular pulses per minute. Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age. Apneic episodes occurred and required treatment equally in the two groups; this lack of an effect was seen for both sexes and all weight groups. Both weight and energy intake were similar. Neurobehavioral development as shown by sleep state, habituation testing, and behavioral assessment at term, 3, 6, and 12 months was similar in the two groups. There was no difference in the incidence of neurologic abnormalities. We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development.
Randomized clinical trial of an oscillating air mattress in preterm infants: effect on apnea, growth, and development.
To investigate claims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development, we performed a randomized clinical trial using a predetermined sample size. Preterm infants weighing from 750 to 1750 gm at birth were randomly assigned, by 250 gm strata, to either a conventional mattress (n = 63) or to an air mattress (n = 59) oscillating at 14 to 16 regular pulses per minute. Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age. Apneic episodes occurred and required treatment equally in the two groups; this lack of an effect was seen for both sexes and all weight groups. Both weight and energy intake were similar. Neurobehavioral development as shown by sleep state, habituation testing, and behavioral assessment at term, 3, 6, and 12 months was similar in the two groups. There was no difference in the incidence of neurologic abnormalities. We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development.
Options:
A: Prophylactic use of kinesthetic stimulation significantly reduces the incidence of apnea and bradycardia, and decreases the need for IPPV.
B: Prophylactic use of kinesthetic stimulation has no significant effect on the incidence of apnea, bradycardia, or the need for IPPV.
C: Prophylactic use of kinesthetic stimulation increases the incidence of apnea and bradycardia, and increases the need for IPPV.
D: Prophylactic use of kinesthetic stimulation significantly improves long-term growth and development outcomes.
|
B
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16
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the use of enteral antibiotic prophylaxis for preventing necrotising enterocolitis in low birth weight and preterm infants? Please answer this question based on the information provided below:
Alterations in stool flora resulting from oral kanamycin prophylaxis of necrotizing enterocolitis.
A prospective controlled trial of oral kanamycin in the prevention of neonatal necrotizing enterocolitis.
Oral gentamicin therapy in the prevention of neonatal necrotizing enterocolitis. A controlled double-blind trial.
The value of prophylactic oral gentamicin sulfate therapy in the prevention of necrotizing enterocolitis (NEC) was evaluated in a group of 42 high-risk neonates over a four-month period in a randomized, double-blind controlled trial. Twenty babies in the treatment group received 2.5 mg/kg of gentamicin sulfate every six hours for one week after birth, and 22 babies received dextrose-and-water placebo in an equivalently small volume. None of the 20 gentamicin-treated babies developed NEC. Four of the control babies did. Two of these babies died, and their diagnosis was pathologically confirmed. This difference in the incidence of NEC between the treatment and control group was significant at the .05 level. These results support the prophylactic use of orally given gentamicin for selected babies at high risk for NEC, particularly those born prematurely and those who have a history of perinatal asphyxia or umbilical artery catheterization or both. Continued surveillance for changes in antimicrobial sensitivity patterns is recommended.
Gentamicin in prophylaxis of neonatal necrotising enterocolitis.
Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants.
AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants.
METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit. The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution. Prophylaxis was started 24 hours before the start of oral feeds. All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs. Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria.
RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035). Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002).
CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence. However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms. Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients.
Options:
A: It significantly reduced the incidence of necrotising enterocolitis and NEC-related deaths without any increase in adverse outcomes.
B: It significantly reduced the incidence of necrotising enterocolitis but had a borderline significant effect on reducing NEC-related deaths and increased the incidence of colonisation with resistant bacteria.
C: It had no significant effect on the incidence of necrotising enterocolitis or NEC-related deaths and did not increase the incidence of colonisation with resistant bacteria.
D: It significantly increased the incidence of necrotising enterocolitis and NEC-related deaths and also increased the incidence of colonisation with resistant bacteria.
|
B
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17
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of therapeutic ultrasound for treating acute perineal pain, persistent perineal pain, and dyspareunia following childbirth? Please answer this question based on the information provided below:
Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial.
Ultrasound and pulsed electromagnetic energy therapies are increasingly used for perineal trauma sustained during childbirth. The study included 414 women with moderate or severe perineal trauma randomly allocated to receive active ultrasound, or active pulsed electromagnetic energy, or corresponding placebo therapies; the allocation was double-blind for each machine. Overall, more than 90% thought that treatment made their problem better. There were no clear differences between the groups in outcome either immediately after treatment, or 10 days or 3 months postpartum, other than more pain associated with pulsed electromagnetic energy treatment at 10 days. Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly. Neither therapy had an effect on perineal oedema or haemorrhoids. The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care.
Options:
A: Therapeutic ultrasound significantly reduced acute perineal pain and dyspareunia, but had no effect on persistent perineal pain.
B: Therapeutic ultrasound showed significant improvement in acute perineal pain and dyspareunia, but the evidence was insufficient to evaluate its overall effectiveness.
C: Therapeutic ultrasound was effective in reducing both acute and persistent perineal pain, as well as dyspareunia.
D: Therapeutic ultrasound had no significant effect on acute perineal pain, persistent perineal pain, or dyspareunia.
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B
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18
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
In preterm infants with apnea, what is the effect of kinesthetic stimulation on the reduction of clinical apnea and bradycardia, the use of mechanical ventilation or continuous positive airways pressure, and neurodevelopmental disability? Please answer this question based on the information provided below:
The effect of vertical pulsating stimulation on apnea of prematurity.
Placing preterm infants suffering idiopathic apnea of prematurity on the VPS had an effect on the infants' respiratory effort and achieved a reduction in the number of apneic episodes secondary to central and mixed apnea. However, VPS offered no benefits in the reduction of obstructive apnea in this study population. Because central apnea has been reported as the predominant type of apnea and VPS is a nontoxic, noninvasive, and easy-to-implement method of alleviating central and mixed apnea types, it seems prudent to give VPS which has the stimulus characteristics to preterm infants experiencing apnea of prematurity before other treatment modalities currently in use are tried. Further studies are warranted to determine if VPS is effective in a continuous long-term treatment for apnea of prematurity, for example, until the end of apnea.
Reduction of sleep apnea and bradycardia in preterm infants on oscillating water beds: a controlled polygraphic study.
The sleep and respiratory patterns of eight apneic preterm infants were polygraphically recorded for 24 hours. This polygraphic study was designed to test and extend our previous finding that gently oscillating water beds reduce apnea in premature infants. The infants who ranged in gestational age from 27 to 32 weeks and in birth weight from 1,077 to 1,650 gm served as their own controls, off and on the water bed. The 24-hour recordings were divided into four time blocks with the infant being placed on the water bed during alternate six-hour periods. Apnea was significantly reduced while the infants were on the oscillating water beds, with the longest apneic periods and those associated with severe bradycardia being reduced the most. Reduction of apnea was most consistent during indeterminate sleep and most pronounced during quiet sleep. Short respiratory pauses and periodic breathing were not significantly reduced. Reductions of central, obstructive, and mixed apneas were approximately equal.
Effect of a rocking bed on apnoea of prematurity.
We describe a rocking bed for use in incubators. Its effect was studied in 12 preterm infants with idiopathic apnoea, using each as his own control. All but one had less apnoea when the bed was rocking than when it was still. Apnoea associated with a significant fall in transcutaneous PO2 was less frequent, and fewer interventions were needed to terminate apnoeic attacks.
Options:
A: Kinesthetic stimulation leads to a significant reduction in clinical apnea and bradycardia, reduces the need for mechanical ventilation or CPAP, and decreases neurodevelopmental disability.
B: Kinesthetic stimulation does not lead to a significant reduction in clinical apnea and bradycardia, does not reduce the need for mechanical ventilation or CPAP, and has no reported effect on neurodevelopmental disability.
C: Kinesthetic stimulation increases the incidence of clinical apnea and bradycardia, increases the need for mechanical ventilation or CPAP, and worsens neurodevelopmental outcomes.
D: Kinesthetic stimulation has mixed results, with some studies showing a reduction in clinical apnea and bradycardia, but no overall reduction in the need for mechanical ventilation or CPAP, and no data on neurodevelopmental outcomes.
|
B
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19
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the conclusion regarding the effectiveness of routine endotracheal intubation at birth in vigorous term meconium-stained infants compared to routine resuscitation including oro-pharyngeal suction? Please answer this question based on the information provided below:
Tracheal suction in meconium stained infants: a randomized controlled study.
We performed a randomized controlled study of the mortality and morbidity of 49 babies born with thick meconium staining of amniotic fluid. These unasphyxiated babies were consecutively born and were admitted to the intensive care unit for observation as routine. The groups were comparable in regard to sex, birth weight, gestational age, maternal factors like anaemia, toxaemia, antepartum haemorrhage, prolonged rupture of membranes, presentation, and interventions including caesarian section. The control group, comprising 26 babies received only oropharyngeal suction, while the intervention group, comprising 23 babies, underwent oropharyngeal suction followed by tracheal suction. There was no significant difference in the mortality or morbidity in form of evidence of air leak or hypoxic ischaemic encephalopathy.
Need for endotracheal intubation and suction in meconium-stained neonates.
In a prospective study, we determined whether routine immediate tracheal aspiration at birth is necessary in meconium-stained but otherwise normal infants delivered vaginally and having a 1-minute Apgar score greater than 8. A total of 572 newborn infants who met these criteria were randomly allocated to one of two groups. All infants underwent oropharyngeal suctioning with a DeLee catheter while the head was still on the perineum. In group I (n = 308) suctioning of the trachea under direct vision was performed instantly at birth; in group II (n = 264) this procedure was not done. There was no mortality among infants in the study, but morbidity, mainly pulmonary and laryngeal disorders, occurred in six of 308 group I infants and in none of the group II infants (P less than 0.025). Immediate tracheal suction is not a harmless intervention, and should be considered superfluous in a vigorous term neonate born with meconium-stained amniotic fluid.
The need for delivery room intubation of thin meconium in the low-risk newborn: a clinical trial.
The delivery room management of meconium-stained amniotic fluid remains controversial. We attempted to determine if intubation of the low-risk newborn with thin meconium affects the incidence of respiratory symptoms. Exclusion criterion included moderate or thick meconium, fetal distress, neonatal depression, or prematurity. Eligible infants were randomized to either an intubation (group I) or to a nonintubation group (group II). The outcome was the presence of respiratory symptoms. Patients were studied from May 1994 to June 1997. There were 8967 births during this period: 7.9% (708/8967) were delivered through meconium. Thin meconium was noted in 50.3% (356/708) of all births. 24/356 infants with thin meconium were excluded for medical criterion. One hundred sixty-three infants were medically eligible but could not be randomized due to lack of consent, late arrival of the team, or obstetrician request. These were placed into intubation (group I B) and nonintubation (group II B) groups. Seventy-seven infants were randomized into group I and 92 infants into group II. From the intubation groups I and I B, one required supplemental oxygen and was weaned to room air in 7 hr. From the nonintubation groups II and II B, two infants required oxygen, weaning to room air in 11 and 46 hr. Comparing birth weight, gestational age, sex, mode of delivery and 5-min Apgar, there were no significant differences. However, the intubation groups had significantly lower 1-min Apgar scores. There was no airway morbidity reported in the intubation groups. In the infant with thin meconium and an otherwise low-risk pregnancy, we were unable to demonstrate a difference in respiratory symptoms with intubation and intratracheal suctioning.
The need for delivery room intubation of thin meconium in the low-risk newborn: a clinical trial.
The delivery room management of meconium-stained amniotic fluid remains controversial. We attempted to determine if intubation of the low-risk newborn with thin meconium affects the incidence of respiratory symptoms. Exclusion criterion included moderate or thick meconium, fetal distress, neonatal depression, or prematurity. Eligible infants were randomized to either an intubation (group I) or to a nonintubation group (group II). The outcome was the presence of respiratory symptoms. Patients were studied from May 1994 to June 1997. There were 8967 births during this period: 7.9% (708/8967) were delivered through meconium. Thin meconium was noted in 50.3% (356/708) of all births. 24/356 infants with thin meconium were excluded for medical criterion. One hundred sixty-three infants were medically eligible but could not be randomized due to lack of consent, late arrival of the team, or obstetrician request. These were placed into intubation (group I B) and nonintubation (group II B) groups. Seventy-seven infants were randomized into group I and 92 infants into group II. From the intubation groups I and I B, one required supplemental oxygen and was weaned to room air in 7 hr. From the nonintubation groups II and II B, two infants required oxygen, weaning to room air in 11 and 46 hr. Comparing birth weight, gestational age, sex, mode of delivery and 5-min Apgar, there were no significant differences. However, the intubation groups had significantly lower 1-min Apgar scores. There was no airway morbidity reported in the intubation groups. In the infant with thin meconium and an otherwise low-risk pregnancy, we were unable to demonstrate a difference in respiratory symptoms with intubation and intratracheal suctioning.
Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial.
OBJECTIVE: Disagreement exists concerning the appropriate delivery room management of the airway of vigorous meconium-stained infants. Some suggest a universal approach to intubation and suctioning of the airway in all such neonates, whereas others advocate a selective approach. We performed this investigation: 1) to assess whether intubation and suctioning of apparently vigorous, meconium-stained neonates would reduce the incidence of meconium aspiration syndrome (MAS); and 2) to determine the frequency of complications from delivery room intubation and suctioning of such infants.
METHODS: Inclusion criteria included: 1) gestational age >/=37 weeks; 2) birth through meconium-stained amniotic fluid of any consistency; and 3) apparent vigor immediately after birth. Subjects were randomized to be intubated and suctioned (INT) or to expectant management (EXP). Primary outcome measures included: 1) the incidence of respiratory distress, including MAS, and 2) the incidence of complications from intubation.
RESULTS: A total of 2094 neonates were enrolled from 12 participating centers (1051 INT and 1043 EXP). Meconium-stained amniotic fluid consistency was similar in both groups. Of the 149 (7.1%) infants that subsequently demonstrated respiratory distress, 62 (3.0%) had MAS and 87 (4.2%) had findings attributed to other disorders. There were no significant differences between groups in the occurrence of MAS (INT = 3.2%; EXP = 2.7%) or in the development of other respiratory disorders (INT = 3.8%; EXP = 4.5%). Of 1098 successfully intubated infants, 42 (3.8%) had a total of 51 complications of the procedure. In all cases, the complications were mild and transient in nature.
CONCLUSIONS: Compared with expectant management, intubation and suctioning of the apparently vigorous meconium-stained infant does not result in a decreased incidence of MAS or other respiratory disorders. Complications of intubation are infrequent and short-lived.
Options:
A: Routine endotracheal intubation significantly reduces mortality and respiratory complications.
B: Routine endotracheal intubation is more beneficial than routine resuscitation including oro-pharyngeal suction.
C: Routine endotracheal intubation has not been shown to be superior to routine resuscitation including oro-pharyngeal suction.
D: Routine endotracheal intubation is recommended for all vigorous term meconium-stained infants.
|
C
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20
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What was the conclusion regarding the effectiveness of teaching pregnant women specific criteria for self-diagnosis of active labour onset in term pregnancy? Please answer this question based on the information provided below:
Recognizing the onset of labor.
An experimental study compared the use of an educational technique based on patient participation with routine instructions to prepare patients to recognize the onset of active labor. The number of visits to the labor suite that resulted in the patient being discharged undelivered was significantly lower in patients who received the educational intervention. The study revealed that, without any increase in time, nurses can prepare patients to make judgments about the need for hospitalization.
Options:
A: The program significantly reduced the number of early admissions to the hospital.
B: The program increased women's confidence and decreased their anxiety.
C: There is insufficient evidence to evaluate the effectiveness of the program.
D: The program resulted in fewer women being sent home because they were not in labour.
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C
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21
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the effects of caregivers using specific criteria to diagnose active labour in term pregnancy compared to routine care? Please answer this question based on the information provided below:
An early labor assessment program: a randomized, controlled trial.
BACKGROUND: Approximately 31 percent of cesarean deliveries in the United States and Canada are performed for dystocia. The aim of this study was to determine the effectiveness of early labor assessment to reduce cesarean birth rates for low-risk nulliparous women.
METHODS: Two hundred and nine low-risk nulliparous women were randomly allocated to either the early labor assessment group or the direct admission to hospital group. Women in the early labor assessment group were evaluated and, if found to be in false or latent labor, were encouraged to go home or walk before admission to the labor unit. Those in the direct admission group were admitted to the labor unit without an assessment. Data were collected and analyzed about method of delivery, duration of labor, intrapartum interventions, and neonatal well-being. Women completed an evaluation of their experience in the early postpartum period.
RESULTS: Significant decreases occurred in duration of labor, use of epidural analgesia for pain, and use of oxytocin to augment labor in the early labor assessment group. These women evaluated their labor and birth experience more positively than women in the direct admission group. No significant differences were found in the frequency of cesarean section or instrumental vaginal delivery for the two groups.
CONCLUSIONS: Early labor assessment has the potential to reduce the number of women receiving oxytocin for augmentation, the rate of epidural analgesia for pain relief, and the duration of the active and second stages of labor, and to improve women's evaluations of their labor and birth experiences.
Options:
A: Women were more likely to receive intrapartum oxytocics and analgesia.
B: Women reported lower levels of control during labour and birth.
C: There were no differences in the rate of caesarean section and other important maternal and neonatal outcomes.
D: Women were less likely to receive intrapartum oxytocics and analgesia, and reported higher levels of control during labour and birth.
|
D
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22
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the effectiveness of routine symphysis-fundal height measurements during antenatal care on pregnancy outcomes? Please answer this question based on the information provided below:
The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial.
A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns.
Options:
A: Symphysis-fundal height measurements significantly improved pregnancy outcomes compared to abdominal palpation alone.
B: Symphysis-fundal height measurements significantly worsened pregnancy outcomes compared to abdominal palpation alone.
C: There was no significant difference in pregnancy outcomes between symphysis-fundal height measurements and abdominal palpation alone.
D: Symphysis-fundal height measurements were found to be harmful and should be avoided during antenatal care.
|
C
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23
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
In preterm or low birth weight infants, what is the impact of gradual versus abrupt discontinuation of supplemental oxygen on the incidence of severe retinopathy of prematurity (ROP)? Please answer this question based on the information provided below:
Retinopathy of prematurity (retrolental fibroplasia) and oxygen. I. Clinical study. II. Further observations on the disease.
Options:
A: Gradual discontinuation significantly reduces the incidence of severe ROP compared to abrupt discontinuation.
B: Abrupt discontinuation significantly reduces the incidence of severe ROP compared to gradual discontinuation.
C: There is no significant difference in the incidence of severe ROP between gradual and abrupt discontinuation.
D: Both methods increase the incidence of severe ROP compared to no supplemental oxygen.
|
A
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24
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
In preterm or low birth weight infants, what were the findings regarding early versus late weaning from supplementary oxygen in terms of neonatal death rates, retinopathy of prematurity, and other long-term outcomes? Please answer this question based on the information provided below:
Oxygen administration and retrolental fibroplasia.
Response of small premature infants to restriction of supplementary oxygen.
Options:
A: Early weaning significantly reduced neonatal death rates and retinopathy of prematurity.
B: Late weaning significantly reduced neonatal death rates and retinopathy of prematurity.
C: There were no significant differences in neonatal death rates or retinopathy of prematurity between early and late weaning.
D: Early weaning significantly improved long-term growth, development, lung, and visual function.
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C
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25
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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In premature infants undergoing extubation, which method is more successful in terms of reducing the likelihood of extubation failure: direct extubation from low rate intermittent positive pressure ventilation (IPPV) or extubation following a period of endotracheal continuous positive airway pressure (CPAP)? Please answer this question based on the information provided below:
Successful direct extubation of very low birth weight infants from low intermittent mandatory ventilation rate.
It is common practice to use endotracheal continuous positive airway pressure for various time periods up to 24 hours before attempting extubation in infants who are mechanically ventilated. A few studies in newborns have indicated that airway resistance is increased through small endotracheal tubes. This increases the work of breathing and the likelihood of subsequent ventilatory failure. In this study, 27 very low birth weight infants who were 1/2 to 28 days old at the time of extubation were randomly divided into two groups. One group of 13 study infants were extubated directly from intermittent mandatory ventilation rates of six to ten per minute, and the other 14 control infants were placed on continuous positive airway pressure through endotracheal tubes for six hours prior to an attempt to extubate. There was no difference between the two groups in gestational age, postnatal age, weight, or severity of lung disease at the time of extubation. All 13 study infants were successfully extubated without significant apnea or respiratory acidosis. Of the 14 control infants, only seven were successfully extubated; six infants had significant apnea and in one infant respiratory acidosis with pH 7.13 and PCO2 65 developed while receiving continuous positive airway pressure (13/13 v 7/14, P less than .005). The seven infants who failed the preextubation trial of continuous positive airway pressure were later extubated from low intermittent mandatory ventilation rates without significant apnea or respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Successful extubation of newborn infants without preextubation trial of continuous positive airway pressure.
Sixty newborn infants who had been mechanically ventilated through 3.0- or 3.5-mm endotracheal tubes were studied to examine the necessity of a preextubation trial of continuous positive airway pressure (CPAP). Thirty randomly assigned study infants were directly extubated from intermittent mandatory ventilation rates of six per minute; 30 randomly assigned control infants were extubated after a six-hour trial of continuous positive airway pressure of 3 cm H2O. Changes in respiratory rate, in PCO2, and in PO2/FIO2 were similar. All 30 study infants tolerated direct extubation without significant apnea or respiratory acidosis. Two study and eight control infants developed apnea during six hours after intermittent mandatory ventilation was discontinued (chi 2 = 4.3, P less than .05). Five control and no study infants had apneic episodes greater than or equal to 0.5 per hour (chi 2 = 5.5, P less than .02). The results of this study suggest that newborn infants may tolerate direct extubation from low intermittent mandatory ventilation rates without a preextubation trial of CPAP. A preextubation trial of CPAP appears to be unnecessary and may cause more frequent apnea in newborn infants if used for more than several hours.
Does continuous positive airway pressure (CPAP) during weaning from intermittent mandatory ventilation in very low birth weight infants have risks or benefits? A controlled trial.
OBJECTIVE: The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants.
STUDY DESIGN: We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%).
RESULTS: There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV.
CONCLUSION: We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.
Options:
A: Direct extubation from low rate IPPV is more successful.
B: Extubation following a period of endotracheal CPAP is more successful.
C: Both methods are equally successful.
D: Neither method is successful in reducing extubation failure.
|
A
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26
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the likely effect of dietary fibre supplements on constipation in pregnant women? Please answer this question based on the information provided below:
Constipation during pregnancy: dietary fibre intake and the effect of fibre supplementation.
Forty women who complained of constipation during the third trimester of pregnancy completed 14-day weighed diet records and bowel function charts over a 4-week period. After 2 weeks of baseline observation the women were randomly allocated into three groups which were asked to take 10 g dietary fibre supplements per day in the form of either a corn-based biscuit (Group A), or as wheat bran (Gp B), or to continue without intervention (Gp C). Mean (+/- s.e.m.) daily dietary fibre intake in the first 2 weeks was similar to that in the general population, at 20.4 +/- 1.2 g, for the whole group, and 21.1 +/- 1.6 g for the 26 women who said they had already increased their dietary fibre intakes in attempts to relieve their symptoms. In the final 2 weeks changes in fibre intakes were: Gp A, mean increase 7.2 +/- 1.0 g per day (P less than 0.001); Gp B, mean increase 9.1 +/- 1.6 g per day (P less than 0.001); Gp C mean decrease 3.50 +/- 1.6 g per day (P less than 0.005). These changes were accompanied by an increase in the number of bowel movements and a change to a softer stool consistency in Gps A and B, with no changes in number of bowel movements or stool consistency in Gp C.
Laxatives in the treatment of constipation in pregnant and breast-feeding mothers.
Options:
A: Fibre supplements have no significant effect on constipation in pregnant women.
B: Fibre supplements decrease the frequency of defaecation and lead to harder stools.
C: Fibre supplements increase the frequency of defaecation and lead to softer stools.
D: Fibre supplements cause adverse effects and worsen constipation in pregnant women.
|
C
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27
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What are the conclusions regarding the administration of furosemide to premature infants treated with indomethacin for symptomatic patent ductus arteriosus? Please answer this question based on the information provided below:
Furosemide does not prevent indomethacin-induced renal side effects in preterm infants.
OBJECTIVE: To determine whether furosemide could prevent renal side effects of indomethacin (INN, indometacin) used for the pharmacologic closure of the patent ductus arteriosus (PDA) in preterm infants.
METHODS: Thirty-six preterm infants with birth weights < 1750 gm affected by hemodynamically significant PDA were randomly assigned to one of two study groups. Group 1 consisted of 18 infants treated with three doses of indomethacin (0.20 mg/kg every 12 hours); each dose was followed by a dose of furosemide (1 mg/kg). Group 2 consisted of 18 infants treated only with the same doses of indomethacin. Body weight, urine output, glomerular filtration rate (GFR), fractional excretion of sodium (FENa+) and potassium (FEK+), and osmolal and free water clearance were evaluated in both groups before, during, and after treatment.
RESULTS: The body weight trend, serum sodium, chloride and potassium concentrations, plasmatic and urinary osmolality were similar during the treatment in both the groups. A significant reduction of urine output (p < 0.01) was detected in group 2 but not in group 1. A significant increase of blood urea nitrogen and serum creatinine was detected at the end of treatment in group 1 compared with group 2. During the treatment, a significantly higher GFR (p < 0.05) was found in group 2 than in group 1. FENa+ and FEK+ were significantly higher (p < 0.05 and p < 0.001, respectively) in group 1 than in group 2 during and after the treatment. The osmolol clearance and free water clearance were significantly higher during and after treatment (p < 0.01 and p < 0.001, respectively) in group 1 than in group 2.
CONCLUSIONS: Our findings show that furosemide cannot prevent the indomethacin-induced renal failure, but it does not have any negative influence on its therapeutic effectiveness.
[Indomethacin and furosemide in closure of ductus arteriosus].
Furosemide prevents the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus.
To determine if furosemide would prevent the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus, 19 premature infants were randomized into two groups: nine received indomethacin alone, and ten received indomethacin followed immediately by furosemide. There was no significant difference between the groups in birth weight, gestational age, postnatal age, and in cardiopulmonary or renal status at the time of study. Infants who received indomethacin and furosemide had significantly higher urine output (P less than 0.05), higher FENa and FECl (P less than 0.01), and higher glomerular filtration rate (P less than 0.05) than those of infants who received indomethacin alone. Seven infants in each group responded to indomethacin therapy with disappearance of PDA murmur and improvement of cardiovascular status. The results of this study suggest that furosemide may prevent the renal side effects of indomethacin therapy and yet not affect the efficacy of indomethacin in the closure of a PDA.
Options:
A: Furosemide significantly increases the risk of failure of ductal closure and is recommended for use.
B: Furosemide does not significantly increase the risk of failure of ductal closure, but there is insufficient evidence to support its use.
C: Furosemide significantly improves mid-term and long-term outcomes in these infants.
D: Furosemide is beneficial for all infants regardless of their initial BUN/creatinine ratio.
|
B
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28
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness and safety of dopamine compared to dobutamine in the treatment of systemic hypotension in preterm infants? Please answer this question based on the information provided below:
Randomized trial comparing dopamine and dobutamine in preterm infants.
The aim of this study was to compare the efficacy of two inotropic infusions in treating low BP in preterm neonates. Forty infants with median gestational age 27 weeks (range 23-33) were studied. At trial entry the infants, who all had a systolic BP < 40 mmHg despite receiving a colloid infusion, were randomized to receive either a dopamine or dobutamine infusion. The infusions were commenced at a rate of 5 micrograms/kg per min and, if necessary, this was increased over the 3 h study period to 15 micrograms/kg per min. There was no significant difference in the gestational or postnatal age or baseline BP of the 20 infants who received dopamine and those 20 who received dobutamine. Three hours after commencing the infusions, although there was no difference in the rate of inotrope infusion between the two groups, the infants who received dopamine had a significantly higher systolic BP, a median of 39 mmHg (range 30-58) compared to a median of 34 mmHg (range 21-46) in the dobutamine group, P < 0.05. In addition, 10 infants who received dopamine, but only 3 who received dobutamine, had a systolic BP > 40 mmHg (P < 0.05). We conclude that dopamine rather than dobutamine infusion is more efficacious in improving the BP of preterm neonates.
Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants.
In a prospective study hemodynamic effects of dobutamine or dopamine (10 micrograms/kg/min) were investigated in 20 preterm infants who had protracted arterial hypotension refractory to volume therapy. Doppler ultrasonography of the superior mesenteric artery (SMA) was applied to verify intestinal perfusion and blood pressure was recorded in parallel. Mean arterial pressure (MAP) raised significantly in both groups (from 31.0 +/- 6.8 to 37.7 +/- 9.8 mm Hg during dobutamine and from 27.7 +/- 3.6 to 36.0 +/- 9.3 mm Hg during dopamine). Mean blood flow velocity increased from 25.8 +/- 13.5 to 31.5 +/- 16 cm/s with dobutamine and from 16.3 +/- 5.0 to 19.0 +/- 6.0 cm/s with dopamine (significant for dobutamine). Vascular resistance of SMA (indicated by resistance index; RI) decreased from 0.81 +/- 0.07 to 0.74 +/- 0.11 for dobutamine and from 0.89 +/- 0.06 to 0.79 +/- 0.07 for dopamine (significant for both groups). These data indicate that in the dose tested here both catecholamines are equally effective in raising MAP and lead to a significant increase of intestinal perfusion. Thus, a negative impact on mesenteric blood supply, predisposing to necrotizing enterocolitis, is not probable.
Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome.
To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome.
Response to dobutamine and dopamine in the hypotensive very preterm infant.
A randomised double blind study was designed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks' gestation. Neonates initially received dopamine or dobutamine 5 micrograms/kg/min. If mean arterial pressure (MAP) remained below 31 mm Hg, the infusion rate was increased in increments of 5 micrograms/kg/min. If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg, it was discontinued and the other drug was administered at the same infusion rate. Left ventricular output (LVO) was measured by pulsed Doppler echocardiography. Mean (SE) MAP increased significantly from 24.4 (1.0) to 32.0 (1.4) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 (1.2) to 37.7 (1.5) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min. The percentage LVO increase was +21 (7)% with dobutamine compared with -14 (8)% with dopamine. Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10, whereas dopamine succeeded in all 10 infants. Six switches from dobutamine to dopamine were thus performed, providing a rise in MAP (29.2 (0.5) to 41.2 (2.0) mm Hg) and drop in LVO (356 (40) to 263 (36) ml/kg/min). These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg; however dopamine does not increase LVO.
Assessment of therapy for arterial hypotension in critically ill preterm infants.
The aim of this paper is to assess the efficacy of albumin and dopamine compared with albumin and dobutamine in treating hypotension in preterm newborn infants (PNI). A randomized, open-label, prospective, cross-over study, was designed on 66 PNI whose weights were between 1,000 to 1,500 g, and persistent hypotension, defined as a mean arterial pressure (MAP) of < 30 mmHg. Infants were randomly allocated to two groups and received a 5% albumin infusion at a dosage of 20 mL/kg, in 30 min. Thereafter, one group received dopamine and the other dobutamine at doses of 5 microg/kg/min. If there was not an increase in MAP values > 30 mmHg, the infusions were increased every 20 min by 2.5 microg/kg/min, up to a maximum of 10 microg/kg/min. Treatment failure was considered when there was no pressure response within 2 hr after the infusion started; then patients were changed to the other catecholamine. Statistical analysis was done with student's t-test, x2, and Fisher's exact probability test. There were no differences between groups in initial features. Overall, MAP was normalized with dopamine in 29 of 33 infants and with dobutamine in 25 of 33 infants (p > 0.05). The initial dosage of 5 microg/kg/min, was adequate in 22 infants treated with dopamine and in 13 treated with dobutamine (p < 0.05). The change from dopamine to dobutamine was successful in three out of four patients, while changing from dobutamine to dopamine was adequate in seven out of eight patients. Dopamine is recognized as the drug of choice to treat hypotension in PNI. Since our results showed only small differences in responses, it is proposed that dobutamine is also as efficacious and useful as dopamine.
Options:
A: Dopamine was more effective than dobutamine in treating systemic hypotension, with fewer infants experiencing treatment failure, but there was no significant difference in neonatal mortality, incidence of severe periventricular haemorrhage, or incidence of tachycardia.
B: Dobutamine was more effective than dopamine in treating systemic hypotension, with fewer infants experiencing treatment failure, and there was a significant difference in neonatal mortality favoring dobutamine.
C: There was no significant difference between dopamine and dobutamine in treating systemic hypotension, neonatal mortality, incidence of severe periventricular haemorrhage, or incidence of tachycardia.
D: Dopamine was less effective than dobutamine in treating systemic hypotension, with more infants experiencing treatment failure, and there was a significant difference in the incidence of tachycardia favoring dopamine.
|
A
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29
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effects of dietary advice to alter salt intake during pregnancy on the risk of pre-eclampsia and its consequences? Please answer this question based on the information provided below:
(Patho)physiological implications of chronic dietary sodium restriction during pregnancy; a longitudinal prospective randomized study.
OBJECTIVE: To study the possible pathophysiological implications of long continued dietary sodium restriction in pregnancy.
DESIGN: Longitudinal prospective randomized study of the effects of a low sodium diet compared with unrestricted sodium intake in pregnancy.
SETTING: Academic Department of Obstetrics and Gynaecology at Sint Radboud Hospital, Nijmegen, The Netherlands.
SUBJECTS: 42 healthy nulliparous women.
INTERVENTION: A low sodium diet (20 mmol sodium daily) started in the 14th week of pregnancy and stopped after delivery.
MAIN OUTCOME MEASURES: Maternal weight gain, food intake, blood pressure, cardiac output, systemic vascular resistance, haematocrit and birthweight.
RESULTS: Total maternal weight gain and dietary energy intake during pregnancy and weight at 1 and 6 weeks postpartum were significantly lower in the low sodium group. Blood pressure during pregnancy did not show major differences. Stroke volume and cardiac output during pregnancy were significantly lower in the low sodium group whereas systemic vascular resistance was significantly higher. Haematocrit values in the low sodium group tended to be lower during pregnancy, but were significantly lower at 1 and 6 weeks postpartum than in the unrestricted group. Placental and birthweights were not significantly different between the two groups.
CONCLUSIONS: Chronic dietary sodium restriction during pregnancy is characterized by a diminished body fat accumulation and a reduction in circulating volume, due to a decrease in both plasma and red cell volume, in combination with a high systemic vascular resistance without major effects on blood pressure and birthweight.
Low sodium diet in pregnancy: effects on maternal nutritional status.
In the present study, besides the effect on blood pressure, the effects of a low sodium diet in pregnancy on maternal energy and nutrient intake, calcium metabolism, zinc and magnesium status, weight gain and body fat storage were investigated. No effect of the low sodium diet in pregnancy on the course of blood pressure and the incidence of hypertensive disorders was observed. The reduction in sodium intake also caused a significant reduction in the intake of energy, protein, carbohydrates, fat, calcium, zinc, magnesium, iron and cholesterol. The reduced intake of calcium, zinc and magnesium in the women on the low sodium diet did not result in significant changes in circulating total calcium, ionized calcium, parathyroid hormone, zinc, alkaline phosphatase or magnesium, probably because of homeostatic adaptations by the kidneys. In the women on the low sodium diet non-significant reductions in weight gain (1.5 kg) and fat mass gain (0.9 kg) over pregnancy were observed. These reductions in weight and fat mass gain were more pronounced (3.4 kg (P = 0.003) and 1.3 kg (P = 0.15), respectively) when only the data of the women with good compliance were analyzed. The use of a low sodium diet in pregnancy did not have significant effects on infant birth weight, placental weight or other pregnancy outcome variables.
Dietary sodium restriction in the prophylaxis of hypertensive disorders of pregnancy: effects on the intake of other nutrients.
Dietary sodium restriction is used in the Netherlands in the prophylaxis of preeclampsia. To study the effects of long-term sodium restriction on the intake of other nutrients and the outcome of pregnancy, 68 healthy nulliparous pregnant women were randomly assigned to either a low-sodium diet (20 mmol/24 h) or an unrestricted diet. The diet was consumed between week 14 of gestation and delivery. The dietary intakes of energy, fat, protein, carbohydrate, sodium, potassium, and calcium were estimated with the dietary-history technique. A low-sodium diet reduced the intake of protein (by approximately 15 g/24 h), fat (by 20 g/24 h), and calcium (by 350 mg/24 h) and tended to decrease the energy intake (by approximately 0.7 MJ/24 h). The intakes of carbohydrate and potassium did not differ between the groups. The maternal weight gain was less in the low-sodium group (6.0 +/- 3.7 compared with 11.7 +/- 4.7 kg). Mean birth weight was not significantly different (3.2 +/- 0.5 compared with 3.4 +/- 0.5 kg).
Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.
Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 < P < 0.98) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P < 0.0001 to P < 0.005). Platelet-bound AVP decreased and Np-OT increased during pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy, whether or not in combination with severe sodium restriction, support the absence of significant non-osmotic stimulation of AVP during pregnancy.
Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial.
OBJECTIVE: To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension.
DESIGN: Multi-centre randomised controlled trial between April 1992 and April 1994.
SETTING: Seven practices of independent midwives and one university hospital.
PARTICIPANTS: The experimental group comprised 184 women given a low sodium diet (< or = 50 mmol sodium/day) and a control group of 177 women given a normal diet. Eligible women for inclusion had had a rise of blood pressure, or excessive weight gain or oedema during the antenatal period. The 361 women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave informed consent at the beginning of their pregnancy to participate in the study.
MAIN OUTCOME MEASURES: The difference between highest diastolic blood pressure after randomisation and diastolic blood pressure at the moment of randomisation; referral and admission to hospital for hypertension.
RESULTS: There was no difference in increase of diastolic blood pressure after randomisation, the percentage of referral and admission to hospital for hypertension, or in obstetric outcome between the two groups. Urinary sodium excretion after randomisation in the normal diet group was significantly higher than in the low sodium group.
CONCLUSION: Prescribing a sodium-restricted diet to prevent or to treat mild pregnancy-induced hypertension is not effective. Therefore there is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non-pregnant individuals.
Options:
A: The trials provided strong evidence that reducing salt intake significantly decreases the risk of pre-eclampsia.
B: The trials provided strong evidence that increasing salt intake significantly decreases the risk of pre-eclampsia.
C: The trials provided insufficient evidence to determine the effects of altering salt intake on the risk of pre-eclampsia.
D: The trials showed that altering salt intake has no effect on the risk of pre-eclampsia.
|
C
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30
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effects of plasma volume expansion for the treatment of women with pre-eclampsia? Please answer this question based on the information provided below:
Haemodynamic changes in gestational proteinuric hypertension: the effects of rapid volume expansion and vasodilator therapy.
Ten patients with gestational proteinuric hypertension were studied with a Swan-Ganz thermodilution haemodynamic catheter before, during and after plasma volume expansion. Five patients were treated with dihydralazine before volume expansion and five after volume expansion. Before treatment all patients had a low pulmonary capillary wedge pressure (PCWP), low cardiac index (CI) and high systemic vascular resistance (SVR). Following volume expansion the PCWP and CI increased, the SVR decreased but the blood pressure (BP) was unchanged. Administration of dihydralazine following volume expansion led to a decrease in PCWP, an increase in CI and a decrease in SVR and BP. Dihydralazine alone caused an increase in heart rate, PCWP, and CI, and a decrease in SVR and BP. Volume expansion, by increasing CI and decreasing SVR, may be of therapeutic benefit in the severely hypertensive pregnant patient with a low cardiac index.
Plasma volume expansion in the treatment of pre-eclampsia.
The effects of plasma volume expansion with hyperosmolar solutions with the use of dextran 40 and plasmanate were studied in a controlled manner in 32 primiparous pre-eclamptic patients. The patients who were being studied received either dextran 40 (Rheomacrodex) or plasmanate in addition to the routine treatment with sedatives, bed rest, and magnesium sulfate when indicated. The patients were randomly assigned by blind draw to control (13), dextran (10), and plasmanate (nine) groups. The renal status of all patients was evaluated prior to volume expansion therapy. Patients were monitored for blood pressure, proteinuria, output of urine, hematocrit, and creatinine clearance. There was significant improvement in hemoconcentration and output of urine, and a trend toward a lowering of the mean arterial blood pressure in patients who were receiving plasmanate or dextran for volume expansion.
Options:
A: Plasma volume expansion significantly improved maternal and fetal outcomes.
B: Plasma volume expansion had no significant effect on maternal and fetal outcomes.
C: There is insufficient evidence to determine the effects of plasma volume expansion on maternal and fetal outcomes.
D: Plasma volume expansion significantly worsened maternal and fetal outcomes.
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C
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31
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the effect of a policy of elective delivery compared to expectant management in term diabetic pregnant women on maternal and perinatal outcomes? Please answer this question based on the information provided below:
Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management.
OBJECTIVE: Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth.
STUDY DESIGN: Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery.
RESULTS: Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 +/- 407 gm) and percentage large for gestational age, as defined by birth weight > or = 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 +/- 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01).
CONCLUSION: In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed.
Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management.
OBJECTIVE: Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth.
STUDY DESIGN: Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery.
RESULTS: Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 +/- 407 gm) and percentage large for gestational age, as defined by birth weight > or = 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 +/- 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01).
CONCLUSION: In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed.
Options:
A: Elective delivery significantly reduced the risk of caesarean section.
B: Elective delivery significantly reduced the risk of macrosomia.
C: Elective delivery significantly increased the risk of maternal morbidity.
D: Elective delivery had no impact on the risk of shoulder dystocia.
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B
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32
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the impact of home versus hospital care and cervical cerclage in women with suspected placenta praevia? Please answer this question based on the information provided below:
Cervical cerclage: an alternative for the management of placenta previa?
OBJECTIVE: Our purpose was to determine whether cervical cerclage reduces the maternal and neonatal morbidity in women with placenta previa.
STUDY DESIGN: Thirty-nine pregnant women with an initial diagnosis of placenta previa at 24 to 30 weeks' gestation were randomly assigned to cervical cerclage (n = 19) or conservative management (n = 20). Subjects were followed up until delivery. Primary outcome measure was gestational age at delivery. Secondary outcome measures were prolongation of pregnancy, number of patients bleeding after being randomly assigned, units of blood transfused, birth weight, hospital stay and costs, and admission to neonatal intensive care unit. Statistical significance was calculated by the Student t test, Fisher's exact probability test, and the chi2 with Yates' correction factor.
RESULTS: No statistically significant differences were observed between the two groups studied.
CONCLUSION: Cervical cerclage does not appear to be an adequate alternative for the management of placenta previa.
Management of the symptomatic placenta previa: a randomized, controlled trial of inpatient versus outpatient expectant management.
OBJECTIVE: Our purpose was to determine the safety, efficacy, and costs of inpatient and outpatient management of symptomatic placenta previa.
STUDY DESIGN: Fifty-three women with the initial diagnosis of placenta previa at 24 to 36 weeks' gestation who required hospitalization for vaginal bleeding were stabilized and then randomized to receive either inpatient or outpatient expectant management. Twenty-seven inpatients were placed at bed rest with minimal ambulation, received weekly corticosteroids until 32 weeks of gestation, and underwent ultrasonographic examination at 2-week intervals to assess fetal growth and placental location. Twenty-six outpatients were discharged home after > or = 72 hours of hospitalization. Each week they also received corticosteroids, until 32 weeks' gestation, and ultrasonographic evaluations. Outpatients with recurrent bleeding were readmitted for evaluation. All subjects who reached 36 weeks' gestation with persistent placenta previa underwent amniocentesis. When fetal lung maturity was present, cesarean delivery was electively performed.
RESULTS: There were insignificant differences between inpatients and outpatients for mean age, parity, race, type of previa (complete or partial), number of prior vaginal bleeding episodes, and initial hemoglobin value. The mean estimated gestational age at enrollment was 29.1 +/- 3.1 (SD) weeks for inpatients and 29.9 +/- 3.1 weeks for outpatients. In eight patients the placenta was found to no longer cover the internal os by 36 weeks' gestation. There were seven patients in each group who did not complete the protocol for initial treatment assignment. The average estimated gestational age at delivery for the inpatients was 34.5 +/- 2.4 weeks and 34.6 +/- 2.3 weeks for the outpatients (p = 0.90), whereas the mean birth weights were 2413.7 +/- 642.7 gm and 2607.8 +/- 587.1 gm, respectively (p = 0.28). Thirty-three patients (62.3%) had recurrent episodes of bleeding, with 26 requiring expeditious cesarean delivery. Four (14.8%) inpatients and one (3.7%) outpatient required blood transfusion (p = 0.67). There was no difference in neonatal morbidity (defined as the presence of respiratory distress syndrome, intracranial hemorrhage, or culture-proved sepsis) between the two groups (relative risk 1.16, 95% confidence interval 0.66 to 2.02). There were no neonatal deaths. The mean number of maternal hospital days differed significantly between the two groups: inpatients required an average of 28.6 +/- 20.3 days and outpatients remained hospitalized for an average of 10.1 +/- 8.5 days (p < 0.0001). Cost analysis based on maternal hospital days reveals a net savings of +15,080 per patient if women with symptomatic placenta previa initially diagnosed before 37 weeks' gestation are treated as outpatients.
CONCLUSIONS: For selected patients, outpatient management of symptomatic placenta previa appears to be an acceptable alternative to traditional conservative expectant inpatient management.
Cervical cerclage for the temporary treatment of patients with placenta previa.
Cervical cerclage as a temporizing measure for the treatment of patients with placenta previa was evaluated in 25 patients admitted to the hospital for vaginal bleeding between 24-30 weeks' gestation and sonographic evidence of a placenta previa. The patients were randomly assigned to either cerclage (13) or conventional management (12). Cerclage patients had significantly better perinatal outcome, as indicated by more advanced gestational age at the time of delivery (34.9 +/- 3.0 versus 31.6 +/- 2.9 weeks; P = .02), larger birth weight (2709 +/- 511 versus 1812 +/- 506 g; P = .002), and fewer neonatal complications (two of 13 versus ten of 12 infants; P = .001). Maternal bleeding was more frequent and severe for patients in the control group. The total hospital cost was less for cerclage patients than for those receiving conventional expectant management ($9898 +/- 3943 versus $27,271 +/- 9901; P = .02). These results support the use of cervical cerclage for the treatment of patients with symptomatic placenta previa early in gestation.
Options:
A: Home care was associated with a significant reduction in maternal mortality, while cervical cerclage showed no benefits.
B: Both home care and cervical cerclage were associated with reduced lengths of stay in hospital antenatally, with cervical cerclage potentially reducing the risk of preterm delivery and low birth weight.
C: Hospital care was found to be significantly more beneficial than home care, and cervical cerclage increased the risk of complications.
D: There was no difference in outcomes between home care and hospital care, and cervical cerclage had no impact on preterm delivery or birth weight.
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B
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33
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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In preterm infants who undergo general anesthesia for surgery, what is the effect of prophylactic caffeine use on the incidence of postoperative apnea, cyanosis, and bradycardia, and are there any significant side effects? Please answer this question based on the information provided below:
The use of caffeine in the control of post-anesthetic apnea in former premature infants.
High-dose caffeine suppresses postoperative apnea in former preterm infants.
Thirty-two former preterm infants (less than or equal to 44 weeks postconceptual age) undergoing inguinal hernia repair were prospectively studied. General inhalational anesthesia with neuromuscular blockade was used. No barbiturates or opioids were given. Infants were randomly divided into two groups. Group 1 received iv caffeine 10 mg/kg immediately after induction of anesthesia. Group 2 received iv saline. Respiratory pattern, heart rate, and SpO2 were monitored using an impedance pneumograph and a pulse oximeter, respectively, for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the drug given. None of the patients who received caffeine developed postoperative bradycardia, prolonged apnea, or periodic breathing, and none had postoperative SpO2 less than 90%. In the control group 13 (81%) developed prolonged apnea 4-6 h postoperatively. Fifty percent of the patients had SpO2 less than 90% at the time. This study shows that iv caffeine 10 mg/kg is effective in the control of apnea in otherwise healthy expremature infants between 37 and 44 weeks of postconceptual age. It is still recommended, however, that all infants at risk be monitored for at least 12 h for apnea and bradycardia following general anesthesia.
Options:
A: Prophylactic caffeine use reduces the incidence of postoperative apnea, cyanosis, and bradycardia without significant side effects.
B: Prophylactic caffeine use increases the incidence of postoperative apnea, cyanosis, and bradycardia and has significant side effects.
C: Prophylactic caffeine use has no effect on the incidence of postoperative apnea, cyanosis, and bradycardia but has significant side effects.
D: Prophylactic caffeine use has no effect on the incidence of postoperative apnea, cyanosis, and bradycardia and has no significant side effects.
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A
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34
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the effectiveness of exogenous gangliosides in the treatment of acute ischaemic stroke? Please answer this question based on the information provided below:
GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study--Hemodilution + Drug.
Eleven of 31 clinical centers participating in the Italian Acute Stroke Study--Hemodilution carried out a preliminary study on the effectiveness of ganglioside GM1 in acute stroke; 502 patients were randomized to GM1 (GM1, n = 121), GM1 plus hemodilution (GM1 + H, n = 128), placebo (P, n = 130), or placebo plus hemodilution (P + H, n = 123) groups less than or equal to 12 hours after onset of a hemispheric cerebral infarct. The patients were treated for 15 days and were evaluated on Days 21 and 120 after the onset of stroke. Intention-to-treat analysis failed to show any differences in neurologic deficit, mortality, or neurologic disability among the groups. Efficacy analysis showed a significantly higher degree of neurologic improvement in GM1 group patients compared with patients in the P group during the first 15 days. GM1-treated patients (GM1 and GM1 + H groups) showed a significantly higher degree of neurologic improvement during the first 10 days compared with the placebo-treated patients (P and P + H groups). These differences were no longer statistically significant at Day 120. Our results provide a rationale for the planning of a larger, multicenter trial of GM1 ganglioside in acute stroke.
GM1 ganglioside therapy in acute ischemic stroke.
[Italian Acute Stroke Study: hemodilution + drug. Presentation of the protocol].
GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study--Hemodilution + Drug.
Eleven of 31 clinical centers participating in the Italian Acute Stroke Study--Hemodilution carried out a preliminary study on the effectiveness of ganglioside GM1 in acute stroke; 502 patients were randomized to GM1 (GM1, n = 121), GM1 plus hemodilution (GM1 + H, n = 128), placebo (P, n = 130), or placebo plus hemodilution (P + H, n = 123) groups less than or equal to 12 hours after onset of a hemispheric cerebral infarct. The patients were treated for 15 days and were evaluated on Days 21 and 120 after the onset of stroke. Intention-to-treat analysis failed to show any differences in neurologic deficit, mortality, or neurologic disability among the groups. Efficacy analysis showed a significantly higher degree of neurologic improvement in GM1 group patients compared with patients in the P group during the first 15 days. GM1-treated patients (GM1 and GM1 + H groups) showed a significantly higher degree of neurologic improvement during the first 10 days compared with the placebo-treated patients (P and P + H groups). These differences were no longer statistically significant at Day 120. Our results provide a rationale for the planning of a larger, multicenter trial of GM1 ganglioside in acute stroke.
Trial of ganglioside GM1 in acute stroke.
Double-blind evaluation of monosialoganglioside (GM1) therapy in stroke.
Monosialoganglioside therapy in stroke.
Effects of GM1 ganglioside in cerebrovascular diseases: a double-blind trial in 40 cases.
A randomized, double-blind trial on the effects of GM1 ganglioside in cerebrovascular diseases was done on 40 patients; the treatment (40 mg/day i.m. injection) began after the acute phase and lasted 6 weeks. 18 cases took the drug and 16 the placebo. The evaluation of the cases was made by graduating the severity of the clinical signs, and some neurophysiological and morphological parameters, i.e., EEGs, flash-evoked potentials and computer tomography scans. We found that the drug, in comparison with the placebo treatment, improved the clinical signs and also the neurophysiological parameters, whereas it was ineffective for the morphological damage. These data seem of some interest in relation to the action of GM1 ganglioside in the processes of neurotransmission and neuronal plasticity as described in the experimental animal.
Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.
BACKGROUND AND PURPOSE: The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke.
METHODS: Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months.
RESULTS: Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences.
CONCLUSIONS: These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke.
Design and baseline results of the monosialoganglioside early stroke trial. The EST Study Group.
BACKGROUND AND PURPOSE: The Early Stroke Trial is a randomized, placebo-controlled, double-masked, multicenter study to assess the safety and efficacy of monosialoganglioside in patients who have suffered an ischemic stroke of the cerebral hemispheres.
METHODS: Only patients who could be evaluated and treated within 5 hours after the onset of stroke were considered; within each center, subjects were stratified by age, sex, and clinical severity. Patients were randomly allocated to receive a specified sequence of intravenous and intramuscular doses of either monosialoganglioside or identical-appearing placebo for 21 days. Patients were followed up for 4 months after randomization. Neurological status was measured primarily by using the Canadian Neurological Scale. After assessing the effect of treatment on survival, the principal measure of efficacy will be the change in neurological status between baseline and the 4-month follow-up among survivors.
RESULTS: Sixteen clinical centers, 15 in Europe and one in North America, entered a total of 792 eligible patients during a 36-month recruitment period (from May 1987 to April 1990). In our series there were more men than women, and the relative frequency of patients increased with advancing age. The most frequently associated cardiovascular conditions were hypertension, atrial fibrillation, and peripheral vascular disease. Approximately 46% of the patients were admitted to a hospital within 1 hour and 81%, within 2 hours after the onset of stroke. About 22% first received the study treatment within 3 hours and 57%, within 4 hours.
CONCLUSIONS: This study demonstrates the feasibility of large-scale trials with the onset of treatment within 5 hours after an ischemic stroke.
A pilot study with monosialoganglioside GM1 on acute cerebral ischemia.
Reported here are the results of an open controlled study on the use of GM1 in cases of ischemic strokes in its acute phase. A statistically significant improvement was observed in cases treated with GM1 for neurological deficits (assessed by Mathew's rating scale, modified by Fritz-Werner) at 21, 60 and 120 days and for disability at 120 days.
Trial of ganglioside GM1 in acute stroke.
Ganglioside GM1 (100 mg) was given daily by intramuscular injection for 28 days in a double-blind placebo controlled trial of acute stroke. No significant difference was detected in a 6 month follow-up period between well matched control and active groups. Although the number of patients studied was small the findings are believed to indicate that GM1 is unlikely to be of value in the treatment of acute stroke in the dose and route of administration used.
[Ganglioside GM1 in early strokes].
The study was taken up to compare the effect of treatment with ganglioside GM1 (Sygen, FIDIA-Italy) and typical treatment in the course of the disease. The study included 98 patients aged 40-82 in good or moderately good physical condition, with the ischaemic stroke confirmed by CT scan, in early stage of stroke (within 48 hours after onset). Patients with severe physical diseases were excluded. The patients were divided at random into two groups. Group I (50 patients) was treated typically and group II (48 patients) was given both typical treatment and ganglioside GM1 administered in 100 mg daily doses over 30 days, i.v. during first 5 days, then i.m. The neurological state was assessed according to the Canadian Neurological Scale (CNS), general fitness according to the Ranking Classification of Neurologic Disability Status (RS) at the admission and after 30 days of the treatment. After 30 days of the treatment no difference between the two groups was found in: 1) mortality, 2) mean survival time, 3) neurological state, 4) patient general fitness. According to the above results the beneficial influence of Sygen treatment of ischaemic stroke was not confirmed.
Ganglioside GM1 in acute ischemic stroke. The SASS Trial.
BACKGROUND AND PURPOSE: We sought to assess the safety and efficacy of ganglioside GM1 in acute (< or = 48 hours), anterior circulation ischemic stroke.
METHODS: We screened more than 5000 patients at 13 centers in a randomized, double-blind, placebo-controlled, parallel-treatment, clinical trial and enrolled 287 patients. They received 100 mg GM1 or placebo intramuscularly daily for 28 days and were evaluated regularly for 84 days. Number of deaths, the Toronto Stroke Scale, and the Barthel Index were primary outcomes; improvements on the Fugl-Meyer Scale and on a neuropsychological battery were secondary outcomes.
RESULTS: The groups were balanced for severity, side of stroke, age, sex, race, years of schooling, prior illness, and depression scores. Analyzable data were available on 275 patients; 217 patients completed the trial. Protocol-specified primary and secondary outcome measures showed no significant difference between treatment arms. However, improvement from baseline in the motor component of the Toronto Stroke Scale favored the GM1-treated group at day 28 when GM1 treatment stopped (P = .020); at day 84, the difference still favored the GM1-treated group (P = .057). All 10 components of the Barthel Index, the Fugl-Meyer Scale, and four of the five tests in the neuropsychological battery also favored the GM1 group. Adverse experiences were similar in the two groups.
CONCLUSIONS: GM1 is safe. However, since only certain post hoc tests showed statistically significant differences or trends favoring GM1, another clinical trial is needed to demonstrate efficacy.
[Trials of monosialoganglioside (Sygen) treatment in ischemic stroke].
65 patients with ischaemic stroke were treated for 6 weeks by intramuscular injections of Sygen--monosialoganglioside 40 mg daily. The results were double-blinded and compared with those in placebo group (Vitamin PP). The results evaluated by Mathew scale did not show any significant differences between both groups. However in the Sygen group we have noticed more patients with very good therapeutic results (almost complete recovery of functions). Immunological studies have not revealed any reaction, which may be considered as a result of allergogenic action of monosialoganglioside.
Options:
A: Gangliosides significantly reduced mortality in acute ischaemic stroke patients.
B: Gangliosides significantly improved disability outcomes without any adverse effects.
C: There is insufficient evidence to support the benefit of gangliosides in acute ischaemic stroke treatment, and caution is advised due to potential adverse effects.
D: Gangliosides significantly improved both mortality and disability outcomes in acute ischaemic stroke patients.
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C
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35
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the efficacy of various treatments for psoriatic arthritis, and which treatments were identified as having well-demonstrated efficacy? Please answer this question based on the information provided below:
A double-blind placebo-controlled study of auranofin in patients with psoriatic arthritis.
Two hundred thirty-eight patients with psoriatic arthritis were entered into a 6-month, multicenter, double-blind trial comparing auranofin and placebo. Polyarthritis (greater than 5 tender joints) was present in 90% of the patients, and 94% were seronegative. Auranofin treatment was statistically superior to placebo treatment, according to physician's global assessment and functional scores. A trend in favor of auranofin treatment was seen for each of the other disease parameters studied. Psoriasis worsened in 6 auranofin-treated patients and in 3 placebo-treated patients. The incidence and nature of other side effects were similar to those observed in similar trials of patients with rheumatoid arthritis. Our observations suggest that the use of auranofin in the treatment of psoriatic arthritis is safe, although its therapeutic advantage over treatment with nonsteroidal antiinflammatory drugs alone is modest.
Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study.
OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy.
METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments.
RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea.
CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.
Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study.
A prospective double-blind, placebo-controlled, randomized study of 24 weeks duration was carried out comparing the efficacy and tolerability of sulphasalazine (SSZ) versus placebo in patients with psoriatic arthritis. A total of 120 patients were included in nine centres. All patients had active disease and fulfilled the criteria of definite psoriatic arthritis of at least 3 months duration. They received either SSZ (2.0 g/day) or placebo. Efficacy variables included pain, patient's overall assessment of joint and skin improvement, morning stiffness, Ritchie articular index, ESR and CRP. An intention-to-treat (ITT) analysis was performed for the 117 patients who qualified (three patients did not qualify due to missing data after baseline). A per-protocol analysis was performed for the 81 patients who completed the 6 months study period (SSZ = 38, placebo = 43). Major reasons for withdrawal were inadequate response (SSZ = 4, placebo = 7) and adverse events (SSZ = 8, placebo = 12). Pain was the only statistically significantly different primary outcome variable at end point in favour of SSZ in the ITT analysis. No significant differences were present in other clinical or biological variables, although there was a trend in favour of SSZ for some variables. SSZ, at a dose of 2.0 g/day, appeared to be a safe treatment in patients with psoriatic arthritis. At this dosage, its efficacy was only demonstrated for the pain variable.
Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study.
OBJECTIVE: To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondylarthropathy.
METHODS: We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population.
RESULTS: Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment.
CONCLUSION: The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.
Sulphasalazine in psoriatic arthritis: a double-blind placebo-controlled study.
Sulphasalazine (SASP) is now accepted as an effective slow-acting antirheumatic drug for treating active rheumatoid arthritis (RA), but has not been previously evaluated in psoriatic arthritis. An earlier open study suggested that it was well tolerated and potentially beneficial. The present double-blind placebo-controlled trial of 30 patients has now confirmed its efficacy. Greater improvement occurred in those patients on active treatment than on placebo, with more benefit being detected in those patients with the symmetrical polyarticular but seronegative pattern of arthritis associated with a high acute-phase response. SASP was stopped in 26% because of side-effects but these were mild. No exacerbation or remission of psoriasis was observed. Further studies are in progress to determine the degree of efficacy of SASP in different clinical subgroups of psoriatic arthritis.
Sulphasalazine in the management of psoriatic arthritis.
There are few 'second-line' drugs available for the treatment of PSA and their use is often limited by toxicity. Thirty-nine patients with active PSA recruited from two rheumatology units were randomly allocated to either enteric-coated sulphasalazine (SASP) or placebo and followed for 24 wk. Six patients in the SASP group and 11 on placebo discontinued therapy before 24 wk. Evaluation of effect of treatment revealed significant improvements in articular index in both groups at 12 wk. By 24 wk the articular index in placebo group was still showing benefit. In addition to articular index the SASP group improved significantly in terms of visual analogue scale, duration of morning stiffness and ESR. SASP is effective in PSA but the partial clinical response to placebo indicates the importance of placebo-controlled studies in this variable disease.
Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial.
OBJECTIVE: Psoriatic arthritis (PsA) is often poorly responsive to 2nd line antirheumatic drug therapy. Sulfasalazine has recently gained wide acceptance in the treatment of rheumatoid arthritis, and beneficial effects have also been noted in ankylosing spondylitis and reactive arthritis. We report a double blind placebo controlled study of sulfasalazine in PsA.
METHODS: Twenty-four patients with active PsA were randomized to receive either sulfasalazine (3 g/day) (n = 10) or placebo (n = 14) for 8 weeks, in a double blind manner, followed by an 8 week open label crossover phase for nonresponding placebo patients.
RESULTS: Compared with placebo controls, sulfasalazine treated patients were significantly improved at Weeks 4 and 8 with respect to physician (p < 0.01) and patient (p < 0.05) global assessments. Duration of morning stiffness was significantly decreased at Week 8 (p < 0.01). Clinical variables of disease activity returned to baseline after a 4 week drug washout period in 5 evaluable patients. Six patients in the placebo group crossed over to an 8 week open label phase and demonstrated significant improvements in joint scores, 50 ft walking time, and global patient assessment. Sulfasalazine treated patients also showed significant improvements in cutaneous involvement.
CONCLUSION: Sulfasalazine was effective in PsA, with efficacy observed as early as the 4th week of treatment. Longterm studies are needed to determine whether such therapy can modify disease outcome.
A double-blind controlled trial of etretinate (Tigason) and ibuprofen in psoriatic arthritis.
Etretinate (Tigason) and ibuprofen have been compared in a double-blind controlled trial in psoriatic arthritis to see if we could confirm a specific action for this vitamin A derivative suggested from earlier uncontrolled studies. Eleven out of 20 patients completed 24 weeks of therapy with etretinate (up to 0.5 mg/kg/day) whereas only 1/20 patients completed 24 weeks of therapy with ibuprofen alone. Etretinate improved skin lesions, and this may have encouraged patients to persist with it. Improvement of statistical significance was seen for articular index in both groups. In addition significant improvement in ESR, haemoglobin, C-reactive protein, and histidine occurred in the etretinate group. The main side effects of etretinate (which may preclude its use at a higher dose in this condition) included cracked and dried lips and sore mouth.
Therapeutic value of colchicine in the treatment of patients with psoriatic arthritis.
OBJECTIVE: To test the hypothesis that colchicine is an effective treatment of psoriatic arthritis.
METHODS: Twenty five patients with psoriatic arthritis were entered into a two centre, double blind, crossover study of 23 weeks' duration comparing the therapeutic effect of colchicine (0.6-1.8 mg/day) with placebo.
RESULTS: No significant difference was noted between colchicine or placebo treatment for the primary outcome measure (Lansbury joint count) or any of the seven secondary outcome measures. No change in the psoriasis was noted during active or placebo treatment. Adverse clinical effects were reported more often during treatment with colchicine (14 patients) than with the placebo (four patients), resulting in the early withdrawal of three patients receiving colchicine from the trial. Increased creatine kinase values, without weakness, occurred during treatment with colchicine (five patients) and placebo (four patients).
CONCLUSIONS: In conclusion, our study did not provide evidence that colchicine is of therapeutic value in the treatment of psoriatic arthritis.
A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.
The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.
Fumaric acid therapy for psoriatic arthritis. A randomized, double-blind, placebo-controlled study.
Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis.
Thirty-seven patients with psoriatic arthritis were entered into a 12-week prospective, controlled, double-blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5-5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate-treated patients. No patients were withdrawn from the study for adverse drug effects.
Options:
A: All agents were found to be equally effective, with no significant differences between them.
B: Parenteral high dose methotrexate and salazopyrin were identified as having well-demonstrated efficacy, while other treatments showed potential but required further trials.
C: Only azathioprine and etretinate were found to be effective, with no significant results for other treatments.
D: Placebo was found to be more effective than any of the treatments tested.
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B
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36
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the comparative outcomes of using condylocephalic nails versus extramedullary implants for the treatment of extracapsular hip fractures in adults? Please answer this question based on the information provided below:
Healing complications after internal fixation of trochanteric hip fractures: the prognostic value of osteoporosis.
In a 3-year prospective randomized trial, the prognostic value of osteoporosis in terms of predicting healing complications due to implant failures or loss of fracture reduction has been studied in 113 patients with inter-trochanteric hip fractures treated with either a sliding screwplate or Ender nailing. According to the Barnet and Nordin's osteoporosis index, 66 patients were considered to have moderate or severe osteoporosis. There were no differences between patients with or without osteoporosis as regards the number of fractures with collapse in varus > 10 degrees, redislocation > 10 mm, or compression exceeding 10 mm. Six months after surgery, 48 patients failed in healing or healed with complications. These cases disclosed increased osteoporosis in comparison with those showing noncomplicated healing. Patients with osteoporosis who had unstable fractures treated by Ender nailing were found to have the worst prognosis for healing complications (p = 0.006). Of the 33 fractures with implant failures, 25 (76%) occurred in patients with osteoporosis (p = 0.04). In patients with osteoporosis, the frequency of mechanical failures was significantly higher in fractures with the device positioned incorrectly. Independently of the device used, patients with unstable trochanteric hip fractures and osteoporotic bone were the group with the highest risk for failures of the implant.
Walking ability after internal fixation of trochanteric hip fractures with Ender nails or sliding screw plate. A comparative study of gait.
The influence of several clinical and radiographic parameters on the functional outcome of 92 patients with trochanteric hip fractures treated at random with either Ender nails or a sliding screw plate (SSP) was prospectively investigated. Apart from other clinical variables such as pain, the use of walking aids, and walking distance, the walking ability of patients was assessed by gait analysis performed on an electronic walkway. The parameters investigated were the maximal vertical force (MVF) and single-limb support phase (SLS). Independent of the type of fixation, no differences were observed between stable and unstable fractures in any of the parameters analyzed six months after surgery. In fractures treated with Ender nails, the use of walking aids and MVF were influenced by a satisfactory fracture reduction. Walking distance was the sole factor correlated with the status of fracture healing. In fractures treated with SSP, the pain was the only clinical variable significantly influenced by the outcome of fracture healing. In trochanteric fractures treated with Ender nails, the quality of fracture reduction was the most valuable predictor of patients' recovery of walking ability.
Clinical features and walking ability in the early postoperative period after treatment of trochanteric hip fractures. Results with special reference to fracture type and surgical treatment.
The purpose of this study was to analyze the functional outcome during the early postoperative period (six weeks) in patients with trochanteric fractures. A consecutive series of 149 patients were randomized to treatment with either the DHS or Ender operative technique. 120 patients were available at review six weeks after surgery. Groups were comparable with respect to age (mean 77 years), sex ratio (73% women), type of fracture (59% and 55% unstable), experience level of the surgeon, prefracture health condition and ambulatory status. During follow-up eight patients died and there were 19 complications of neurologic and cardiovascular types equally spread among the two groups. All four infections were found in the DHS group. Orthopaedic hospital stay averaged 19 days and more patients in the Ender group could return to their previous home at time of discharge. At the six week visit 14% in the Ender group compared to 33% in the DHS group had not recovered functional walking distance (less than 15 m). All patients in the Ender group managed to walk, but 11% of the patients in the DHS group could not walk. Walking ability was most impaired for unstable fractures. It is concluded that the Ender technique will involve less operative trauma (shorter operations with less blood loss) and in the early postoperative period it can provide better conditions for walking and less need for further hospitalization than the DHS technique.
A prospective randomized study of the use of sliding hip screws and Ender nails for trochanteric fractures of the femur.
The functional outcome of trochanteric hip fractures was investigated prospectively in a group of 92 patients treated at random with either Ender nails or a sliding hip screw. Apart from clinical variables, the walking ability of the patients was assessed by gait analysis performed on an electronic walkway. No perioperative complications were noted. The patients in the Ender group had significantly less blood loss and a shorter operation time than the patients treated with the sliding hip screw, indicating that the former method is more gentle as a primary intervention. However, over time there were more reoperations in the Ender group and the functional outcome, including gait analysis after 6 months, showed more favourable results for fractures treated with the sliding hip screw. We therefore recommend the sliding hip screw for an optimal functional result.
Postoperative improvement of walking capacity in patients with trochanteric hip fracture: a prospective analysis 3 and 6 months after surgery.
Between 1982-1985, 149 patients with trochanteric fractures were randomly selected for treatment with either Ender nails or a sliding nail plate. Ninety-two patients were able to perform walkway tests on an electronic walkway and were considered the best prospects for rehabilitation. Thirty-seven patients' fractures were stabilized with Ender nails and 55 with a sliding nail plate. Gait analyses were made at 3 and 6 months after surgery. Change in walking capacity based on four parameters (walking aids, walking distance, maximal vertical force, and single limb support) was compared to changes in clinical and radiographic parameters at 3 and 6 months after surgery. In all, less than half of the patients had achieved their preoperative status 3 months after surgery. Between 3 and 6 months postoperatively, 42 patients experienced less pain, 23 improved in range of hip motion, and 12 improved in strength. According to multivariate regression analysis, the significant factors associated with improvement in walking capacity during this period were an unstable fracture type (p = 0.003), improvement of hip strength (p = 0.006), and improvement of pain (p = 0.03). In conclusion, rehabilitation of patients with trochanteric fractures, particularly in those patients with unstable fractures, should be continued for more than 3 months after surgery.
The use of Ender's pins in extracapsular fractures of the hip.
In October 1976 a randomized, paired, prospective study comparing the compression sliding hip screw with Ender's pins in the treatment of extracapsular hip fractures was begun on the orthopaedic service at San Francisco General Hospital. The results in 100 patients with a minimum follow-up of six months showed that Ender's procedure required less operative time, had less blood loss, and had a lower postoperative incidence of medical complications. A 26 per cent incidence of technical problems with Ender's pins (such as postoperative backing-out of the pin) required reoperation in 16 per cent of the patients compared with an 8 per cent rate of reoperation in patients treated with the compression screw. The majority of these complications occurred in unstable fractures. There were no deep infections in the patients with Ender's pins but a 6 per cent incidence of deep infection was seen in those with the hip screws. There were no non-unions in either group. Although hip function at follow-up was equal in both groups, there was a 41 per cent incidence of postoperative pain and stiffness of the knee in the group with Ender's pins. It is our opinion that Ender's pins are a valuable addition to the armamentarium of surgeons treating extracapsular fractures of the hip and are ideally suited for elderly patients with stable fractures, particularly if the surgical risk is high. They must be used with caution in unstable fractures and postoperative protection in traction may be necessary. However, the occasional external rotation deformity and the high incidence of problems with the knee makes their use in younger, more active patients less desirable than the compression hip screw unless their unique advantages justify their use.
A comparison of nail-plate fixation and Ender's nailing in pertrochanteric fractures.
A randomized comparison was made of condylocephalic (Ender) nails and a nail-plate technique (McLaughlin) for fixation of trochanteric fractures, to evaluate the consumption of acute hospital bed-days, number of reoperations, peroperative blood loss, and operation time. Reoperations were performed in 30% of the Ender group and in 10% of the McLaughlin group and blood loss was doubled for the McLaughlin method. Our study has shown, that in our hands, patients operated on with Ender nails had more reoperations, but in spite of this the total cost, in the form of days in hospital or operation time was not increased.
[Pertrochanteric fractures. Comparison between 2 surgical methods of internal fixation].
Intertrochanteric fractures: a comparison between fixation with a two-piece nail plate and Ender's nails.
The progress of 182 patients who presented with intertrochanteric fractures was followed over a six month period. Eighty-seven patients were treated using Thornton/McLaughlin nail plates and 95 were treated using Ender's intramedullary nails. Each fracture was classified according to radiological position and mechanical stability. The results show that the more unstable fractures are more likely to develop unsatisfactory results. Post operatively, the different mechanical complications have been recorded at various stages. Those fractures fixed with a nail plate tended to develop varus deformity resulting from either bony collapse around the implant or implant failure, whereas those fixed with Ender's nails did not develop deformity at the fracture site but encountered distal migration of the nails at the knee. The use of a classification system in predicting post operative mechanical complications is considered, and the comparative merits and disadvantages of the two fixation systems is discussed, with suggestions for improvement in operative technique.
Sliding screw in the treatment of trochanteric and subtrochanteric fractures.
From spring 1979 all patients with trochanteric and subtrochanteric fractures treated at Aarhus County Hospital have been operated on with the sliding nail, and the patients' progress has been followed for 1 year. In this article the results from the 92 first operations are compared with the results from a controlled trial comparing Ender's nailing and McLaughlin's nail-plate fixation. The latter series originated from the same department but from 1976 until 1978. It was bound that the time of anaesthesia in the Ender, the McLaughlin and in the sliding-nail group wad 125, 131 and 145 minutes respectively. There was no significant difference in the occurrence of post-operative complications between the 3 groups. In the Ender group 56 per cent of the patients had technical complications compared with 23 per cent in the McLaughlin group. In the Ender group 14 per cent had second operations compared with only 3 per cent in the two other groups. The results at the 1-year follow-up examination were the best in the sliding-nail group. It was concluded that the use of the sliding nail carried great advantages compared with Ender nailing and McLaughlin nail plating.
Trochanteric and subtrochanteric fractures. The operative results in a prospective and comparative study of Ender nailing and McLaughlin Osteosynthesis.
A comparative and prospective study was performed in order to evaluate the advantages or disadvantages of the Ender operation in comparison with the McLaughlin technique. The series included 145 patients, 72 operated by the Ender method, and 73 by the McLaughlin method. There were no differences between the two groups as regards anaesthesia time, operation time, mean stay in hospital, morbidity and mortality. Technical problems were encountered in 40 of the Ender operated fractures (56 per cent), whereas the figure for the patients treated with the McLaughlin method was 17 (23 per cent). Ten (14 per cent) patients in the Ender group but only 2 (3 per cent) in the McLaughlin group needed re-operation. Three deep infections occurred in the McLaughlin group, but non in the Ender group. It was concluded that the only advantage which could be demonstrated in the Ender group was a low infection rate. Many disadvantages were revealed, the most outstanding being the many technical problems encountered and the great number of re-operations required.
Trochanteric and subtrochanteric fractures. One year follow-up of a prospective study of Ender and Mclaughlin osteosynthesis.
The clinical and social status of 110 patients with trochanteric and subtrochanteric fractures was evaluated in a prospective and comparative study 1 year after Ender or McLaughlin osteosynthesis. In both groups the mortality rate during the first year was 21 per cent. There were no significant differences between the two groups concerning pain, hip movement, walking ability of the social status of the patients. Of the 110 patients surviving the first year, 35 per cent were unable to walk, 20 per cent walked with a cane or crutches and 30 per cent had periodic pains in the hip or knee. About 20 per cent of the patients admitted from their own home now lived in nursing homes.
Intertrochanteric fracture of the hip. Comparison of nail-plate fixation and Ender's nailing.
Between April 1979 and August 1983, 201 patients with intertrochanteric fractures of the hip were admitted to Haife Medical Center (Rothschild), Israel. These patients were randomely divided into two groups: 104 patients underwent fixation with a compression screw and plate (Richard's Co.) and 97 patients underwent fixation with Ender's nails. The results of both groups were analyzed and evaluated clinically, economically, and socially. There were differences in operative time, incidence of infection, local complications, and functional capacity, but, on the other hand, no difference in the length of hospital stay. The perioperative mortality was significantly higher in the group that underwent fixation with Ender nails (seven to one), but the overall mortality was the same for both groups. The advantages of the Ender method are a quicker surgical procedure, diminished blood loss, and practically no risk of deep infection. The fixation with compression screw and plate assures a better anatomical reduction of the hip with fewer local complications and a better functional result, but carries a higher risk of infection.
Treatment of intertrochanteric fractures: comparison of Ender nails and sliding screw plates.
The results of two fixation devices for the treatment of intertrochanteric fractures were compared in 220 patients--163 women and 57 men with a mean age of 81 +/- 10 years. One hundred and one patients were randomized to Ender nailing and 119 to fixation with a sliding screw plate (SSP). The two treatment groups were equal with respect to important preinjury variables. The two methods did not differ in operating time or perioperative blood loss. The proportions of good reduction of the fractures and of good positioning of the internal fixation devices were equal in the two groups. But the complication rate and the reoperation rate were more than twice as high in the Ender group than in the SSP group. The outcome at 1-year follow-up was approximately equal in the two groups.
Unstable intertrochanteric fractures of the hip. Treatment with Ender pins compared with a compression hip-screw.
In a prospective, consecutive, randomized study of the treatment of unstable intertrochanteric fractures of the hip, the use of Ender pins was compared with the use of the compression hip-screw. There were more than 100 patients in each treatment group. The patients who were alive six months postoperatively were evaluated. The number of secondary operations was much higher in the patients who were treated with Ender pins, and a considerably higher number of those patients had loss of fixation. The use of Ender pins that were too long and a history of a fracture before the operation in which Ender pins were used were statistically significant predictors of secondary operations.
Options:
A: Condylocephalic nails result in fewer complications and better overall outcomes compared to extramedullary implants.
B: Condylocephalic nails have a higher rate of deep wound sepsis and longer surgery times compared to extramedullary implants.
C: Condylocephalic nails have advantages in intra-operative outcomes but lead to higher rates of re-operation, fracture healing complications, residual pain, and limb deformity compared to extramedullary implants.
D: There is no significant difference in outcomes between condylocephalic nails and extramedullary implants.
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C
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37
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the effects of using radiant warmers compared to incubators on fluid and electrolyte balance, neonatal morbidity, and mortality in newborn infants? Please answer this question based on the information provided below:
Combined effect of radiant warmer and phototherapy on insensible water loss in low-birth-weight infants.
Heat balance in premature infants: comparative effects of convectively heated incubator and radiant warmer, with without plastic heat shield.
Insensible water loss, oxygen consumption, and carbon dioxide production were measured in eight premature infants under four different conditions: in conventional single-walled incubator with and without plastic heat shield, and under radiant warmer with and without heat shield. IWL was greater under the radiant warmer (3.40 +/- 1.50 ml/kg/hour, mean +/- SD) than in the incubator (2.37 +/- 1.15 ml/kg/hour) when both were compared without heat shield. Addition of the heat shield reduced IWL in the incubator (2.13 +/- 0.76 ml/kg/hour) but not under the radiant warmer (3.37 +/- 0.94 ml/kg/hour). There were no significant differences in VO2 or respiratory quotient between any two of the four study conditions.
Minimal oxygen consumption in infants cared for under overhead radiant warmers compared with conventional incubators.
Infants under radiant warmers have large increases in insensible water loss compared with infants in single wall incubators. To answer the question of whether or not a minimal rate of oxygen consumption could be achieved under overhead radiant warmers, we measured oxygen consumption, carbon dioxide production, and abdominal skin, cheek, rectal, thigh, and environmental temperature in ten healthy newborn infants in incubators and radiant warmers, using each infant as his/her own control. The minimal VO2 ranged from 4.41 to 8.87 and from 4.35 to 9.06 cc/kg/minute in the incubator and radiant warmer, respectively. The differences were clearly not significant (paired Student t-test, P greater than 0.60). There were no significant differences between the respiratory quotients, VCO2, or abdominal skin, check, rectal or environmental temperatures. These data support the hypothesis that a thermoneutral environment can be provided with a radiant warmer and imply that large increases in insensible water loss can occur without affecting minimal oxygen consumption.
Relative efficacy of an incubator and an open warmer in producing thermoneutrality for the small premature infant.
To determine which warming system more closely approximates a neutral thermal environment, the oxygen consumption of 16 premature babies, weighing less than 1,500 gm each, was measured in a convectively heated incubator and under an open radiant warmer. Both systems were controlled to maintain a skin temperature of 36 C. The oxygen consumption of the infants was significantly higher under the radiant warmer. This result is in agreement with published data for this group of premature infants.
Oxygen consumption and insensible water loss in premature infants under radiant heaters.
Oxygen consumption ((Vo2), carbon dioxide production (Vco2), and insensible water loss (IWL) were measured simultaneously in nine nondistressed, appropriately grown, premature infants less than 2 weeks old, nursed in a conventional, blow-warmed incubator, and were compared with measurements made on the same infants under a radiant heater. The infants had a pronounced increase (148% on average) in IWL when under the radiant heater (P < .001) whereas Vo2 increased by only 4.6% (P = .073). Abdominal skin temperature (servocontrolled to maintain 36.5 C) and esophageal temperature were the same under both conditions, but ambient air temperature was 0.7 C higher in the incubator (P < 05). Although a positive correlation was found between the increase in IWL and the change in Vo2 (r = .75, P < .01), the large increase in IWL (and, therefore, evaporative heat loss) under the radiant heater is out of proportion to, and cannot be accounted for, by the change in metabolic heat production. The heat transfer processes involved in maintaining body temperature constant under these conditions require further study.
Energy metabolism and substrate utilization in low birth weight neonates under radiant warmers.
We evaluated the metabolic response to the thermal demands of an open radiant warmer device, as distinct from convection incubator, in 13 healthy premature infants (1.395 +/- 169 g, 28 +/- 12 days of age, mean +/- SD). Metabolic rate was 10% higher for infants under the radiant warmer than in the incubator (2.60 +/- 0.4 v 2.36 +/- 0.3 kcal/kg/h; P less than .05). The radiant warmer also induced a small (4%), but significant, increase in nonprotein respiratory quotient (0.94 +/- 0.1 v 0.90 +/- 0.1; P less than .05) and a 13% increase in carbon dioxide production (8.26 +/- 1.1 v 7.31 +/- 1.1 mL/kg/min; P less than .05). Subcutaneous fat accumulation (estimated from 60-second skin-fold thickness measurements) was greater under the radiant warmer than in the incubator (0.08 +/- 0.05 v 0.04 +/- 0.04 mm/d; P less than .05). Under the warmer, the infant's mean skin temperatures and core temperatures were normal and similar to those found in the incubator, but the foot temperature was on average 0.6 degrees C cooler. The average rate of weight gain (18 g/kg/d) was the same in the radiant environment. The pattern of the elevated metabolic rate, shift of respiratory quotient coupled with the accumulation of subcutaneous fat, and cool extremities of infants under the radiant warmer may represent a physiologic adaptive response to thermal stress. However, the reasons for the elevated metabolic rate are unclear, because activation of the sympathetic nervous system with the release of catecholamines is not apparently involved.(ABSTRACT TRUNCATED AT 250 WORDS)
A clinical comparison of radiant warmer and incubator care for preterm infants from birth to 1800 grams.
OBJECTIVE: The objective of this study was to compare radiant warmer and incubator care for preterm infants from birth with respect to temperature control and weight gain.
METHODS: Sixty preterm infants <33 weeks' gestation were randomized at birth to radiant warmer or incubator care. The initial goal was to maintain abdominal temperature at 36.8 degrees C in both groups and axillary temperature at 36.8 to 37.3 degrees C; air servocontrol was used for incubator infants. Infants in both groups received added humidity for 5 days if their weight was <1000 g and for 3 days if they weighed between 1000 and 1249 g. During a 3-hour period on days 1 to 7, recordings of abdominal, forehead, and foot temperatures were obtained. The percentage of the recording time during which the abdominal temperature was in the target range of between 36 degrees C and 37.5 degrees C was determined as an indicator of temperature control. Weight gain from birth to 1800 g was compared. Secondary outcomes included fluid balance and clinical events.
RESULTS: There were 30 infants in each group; 48 were <1500 g (of whom 17 were <1000 g). There were no significant differences in birth weight, gestation, gender, or illness severity scores in the 2 groups. Significant differences in temperature control were noted on day 1. Although admission temperatures were similar, lower abdominal temperatures were noted in the first 2 hours of life in the incubator group (medians were 36.6 degrees C and 35.9 degrees C in the radiant warmer and incubator groups, respectively). Similarly, mean abdominal temperatures during the 3-hour recording on day 1 were lower in the incubator group, and infants in this group spent a significantly greater percentage of the recording time with temperatures outside the target range (17.3% compared with 0.88%). Other temperature recordings from the forehead and foot were not significantly different in the groups. Fluid intakes were higher for infants under radiant warmer on days 2, 3, and 4, and the difference amounted to a mean of 12.8 mL/kg/d. Maximum sodium levels in the first week were similar in the 2 groups. Mean weight gain was 17.4 g/kg/d for the radiant warmer group and 17.1 g/kg/d for the incubator group; days to regain birth weight and length of hospital stay were not significantly different. Greater numbers of infants in the radiant warmer group required phototherapy, and adverse events (which included death, necrotizing enterocolitis, chronic lung disease, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or retinopathy requiring laser treatment) were less frequent in the radiant warmer group (1 infant compared with 8 in the incubator group; relative risk 0.1; 95% confidence intervals: 0.01-0.82).
CONCLUSIONS: This study has shown differences in abdominal temperatures on day 1 and outcome, although the latter finding should be viewed with caution because of the sample size. The results indicate benefits for the initial use of the radiant warmer after birth. Although fluid requirements were higher in the radiant warmer group for days 2 through 4, the increased fluid volumes were given without apparent adverse effect.
[Incubator care versus "open care" in the warming bed for very small premature infants].
Options:
A: Radiant warmers significantly reduce insensible water loss (IWL) and oxygen consumption compared to incubators.
B: Radiant warmers significantly increase insensible water loss (IWL) compared to incubators, with no significant difference in oxygen consumption.
C: Radiant warmers have no significant effect on insensible water loss (IWL) or oxygen consumption compared to incubators.
D: Radiant warmers significantly increase both insensible water loss (IWL) and oxygen consumption compared to incubators.
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B
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38
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the use of high frequency oscillatory ventilation (HFOV) compared to conventional ventilation (CV) in preterm infants with severe pulmonary dysfunction? Please answer this question based on the information provided below:
Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. HiFO Study Group.
We conducted a multicenter, prospective, noncrossover, randomized study to determine whether high-frequency oscillatory ventilation (HFOV) would decrease the development or progression of air leak syndrome in infants with severe respiratory distress syndrome. Air leak syndrome was defined as pulmonary interstitial emphysema or gross air leak such as pneumothorax. Infants were eligible for study entry if they were less than 48 hours of age and had severe respiratory distress syndrome, defined by peak inspiratory pressure or the presence of air leak syndrome. Infants who weighed > or = 0.5 kg at birth were randomly assigned to receive either conventional ventilation (CV) or HFOV. HFOV was provided by a ventilator that operated at 15 Hz, with a 1:2 inspiratory/expiratory ratio and no background tidal breaths. Severity of pulmonary interstitial emphysema was scored independently by two neonatologists unaware of the infants' ventilatory group. Gross air leak severity was scored according to the number of chest tubes required and duration of air leak. Eighty-six infants received HFOV; 90 received CV. During the first 24 hours of the study, patients in the HFOV group received significantly higher mean airway pressure and lower inspired oxygen concentration, had significantly lower arterial carbon dioxide tension, and had a higher ratio of arterial to alveolar oxygen tension. When the HFOV and CV groups were compared with control for birth weight strata, study site, and inborn versus outborn status, HFOV significantly reduced the development of air leak syndrome in those patients who entered the study without the syndrome. We conclude that HFOV, when the strategy employed in this study is used, provides effective ventilation, improves oxygenation, and significantly reduces the development of air leak syndrome in infants with severe respiratory distress syndrome.
Options:
A: HFOV significantly reduced the incidence of any new pulmonary air leak (PAL) without increasing the risk of intraventricular hemorrhage (IVH).
B: HFOV significantly reduced the incidence of any new pulmonary air leak (PAL) but increased the risk of intraventricular hemorrhage (IVH).
C: HFOV did not show any significant difference in the incidence of new pulmonary air leak (PAL) or intraventricular hemorrhage (IVH) compared to CV.
D: HFOV significantly increased the incidence of any new pulmonary air leak (PAL) and intraventricular hemorrhage (IVH).
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B
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39
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the impact of the position of the tip of an umbilical arterial catheter on the frequency of ischemic events, aortic thrombosis, intraventricular hemorrhage, mortality, or necrotising enterocolitis in newborn infants? Please answer this question based on the information provided below:
Umbilical artery catheters: high, low, or no.
Randomized trial of umbilical arterial catheter position: clinical outcome.
In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the "high" group and nine in the "low" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.
Randomised trial of umbilical arterial catheter position: Doppler ultrasound findings.
Umbilical arterial catheters (UAC) were randomly assigned in 69 infants to a high (n = 36) or to a low (n = 33) position. Serial Doppler ultrasound measurements of blood flow velocity in their superior mesenteric arteries, coeliac axis, renal arteries, and anterior cerebral arteries were then obtained. There were no differences in blood flow velocity between high and low UAC groups on days 1, 3, and 7. At 2 weeks, those infants with a high UAC still in place had significantly higher velocities in the mesenteric artery than those infants who had no catheter in place. Infants with high UACs remaining in place for more than 7 days were found to have an increase in abdominal distension and tenderness, whereas this was not the case for those with low UACs. Catheter position has no effect on visceral blood flow if the UAC stays in place for one week or less, whereas prolonged use of a high UAC may alter intestinal blood flow and increase the incidence of abdominal symptoms.
Low positioning of umbilical-artery catheters increases associated complications in newborn infants.
We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P less than 0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions.
The association of heparin exposure with intraventricular hemorrhage among very low birth weight infants.
To determine whether there is a relationship between exposure to heparin and an increased risk of intraventricular hemorrhage (IVH), we analyzed data from a cohort of infants who had been subjects in a randomized clinical trial of umbilical artery catheter placement. Data from 862 infants who survived the first 6 days of life were used for analysis. The incidence of IVH (grades 1 through 4) was 28.6%. The mean (SD) birth weight for infants with IVH was 954 gm (247 gm) compared with 1053 gm (253 gm) among infants without IVH (p < 0.01). The mean (SD) heparin intake among infants with an IVH was 83.5 units/kg/day (48.7) compared with 59.4 units/kg/day (48.7) among infants without an IVH (p < 0.01). With the use of logistic regression modeling to adjust for a number of potentially confounding variables, including fluid intake and birth weight, we observed an odds ratio for an IVH of 1.96 (95% confidence interval = 1.32, 2.91) for infants with second through fourth quartile intakes of heparin compared with that for infants with first quartile heparin intakes. Although we cannot rule out the possibility that the observations from this model may be confounded by factors associated with the severity of illness of the infant, these data support the findings of previous reports of an association between heparin exposure and the risk for an IVH.
Relationship of intraventricular hemorrhage or death with the level of umbilical artery catheter placement: a multicenter randomized clinical trial. Umbilical Artery Catheter Trial Study Group.
Umbilical artery catheters are frequently used in the care of very low birth weight neonates to monitor arterial blood gas values. Historically, catheters with the tip placed low, in the abdominal aorta, have been associated with an increased risk of peripheral vascular complications. Recently, a report suggested that catheters placed high, in the thoracic aorta, were associated with an increased risk of intraventricular hemorrhage. To determine whether there is an association between the placement of an umbilical artery catheter high, in the thoracic aorta, and the occurrence of intraventricular hemorrhage (grades II through IV) or death within the first 5 days of life, a multicenter randomized trial was conducted. Nine hundred seventy neonates weighing 500 through 1499 g were randomly assigned to receive either high catheters, in the thoracic aorta closest to the sixth to eight thoracic vertebra, or low catheters, in the abdominal aorta closest to the third to fifth lumbar vertebra. The incidence of the primary outcome (intraventricular hemorrhage grades II through IV and/or death) was 25.8% among newborns with high catheters and 23.1% in those with low catheters (relative risk = 1.12, 95% confidence interval = 0.89, 1.39). However, a significant interaction was observed between the level of catheter placement and birth weight for neonates weighing 750 through 999 g and those weighing 1000 through 1499 g. The subgroup of neonates weighing 750 to 1000 g had a relative risk of the primary outcome of 0.72 (95% confidence interval = 0.49, 1.07), while those weighing 1000 through 1499 g had a relative risk of 2.02 (1.21, 2.36).(ABSTRACT TRUNCATED AT 250 WORDS)
Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position.
Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs.
Options:
A: High placed umbilical artery catheters are associated with a higher incidence of clinical vascular complications and adverse sequelae.
B: Low placed umbilical artery catheters are associated with a lower incidence of clinical vascular complications and adverse sequelae.
C: High placed umbilical artery catheters are associated with a lower incidence of clinical vascular complications, without an increase in adverse sequelae.
D: The position of the umbilical artery catheter tip does not influence the frequency of ischemic events, aortic thrombosis, intraventricular hemorrhage, mortality, or necrotising enterocolitis.
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C
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40
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effect of heparin in fluids infused through an umbilical arterial catheter in newborn infants on the incidence of catheter occlusion, aortic thrombosis, and other clinical outcomes? Please answer this question based on the information provided below:
Effect of adding heparin in very low concentration to the infusate to prolong the patency of umbilical artery catheters.
A randomized controlled study was done to determine whether the addition of heparin, in very low concentration (0.25 U/ml), to fluids administered through an umbilical artery catheter (UAC) would affect the duration of catheter patency. UAC occlusion occurred in 2 of 15 patients in the heparin group and in 11 of 15 patients in the control group (p = 0.001). Using life-table analysis, the functional life span of UAC was estimated. On day 8, 100% of UACs in heparin group and 9% of UACs in control group were patent (p < 0.05). Coagulation profile remained unaltered after addition of heparin compared with that before the start of the therapy. There was no difference in the incidence of subependymal intraventricular hemorrhage between the two groups. It is concluded that heparin in such low concentration is effective in prolonging duration of UAC patency without causing adverse effects.
Continuous versus intermittent heparin infusion of umbilical artery catheters in the newborn infant.
Heparin and the risk of intraventricular hemorrhage in premature infants.
OBJECTIVE: This study was carried out to determine whether the routine use of low-dose heparin in umbilical catheter infusates increases the risk of intraventricular hemorrhage or alters the coagulation profile in premature infants.
METHODS: In a randomized, blinded trial, 113 infants born at less than 31 weeks' gestation were assigned to receive, in their umbilical catheter infusate, either 1 unit of heparin per milliliter (n = 55) or no heparin (n = 58). Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and antithrombin III activity levels were determined at the start and the completion of the study. Cranial ultrasonography was performed during the first week of life.
RESULTS: There was no difference in the incidence of intraventricular hemorrhage between the heparin and no heparin groups, 35.8% and 31.5%, respectively (p = 0.6). Similarly, no difference was detected in the incidence of severe intraventricular hemorrhage (grades III/IV). Prothrombin time, activated partial thromboplastin time, and fibrinogen levels were not significantly different between the two groups. However, the use of heparin was associated with a lower antithrombin III activity level. Antenatal indomethacin use was associated with a 2.9 increased risk of intraventricular hemorrhage (95% confidence interval, 1.15 to 7.17).
CONCLUSION: A low dose of heparin added to umbilical catheter infusates does not increase the incidence or severity of intraventricular hemorrhage or significantly alter the coagulation profile in premature infants.
Prevention of umbilical artery catheter clots with heparinized infusates.
49 neonates requiring umbilical artery catheters (UACs) were randomly assigned to receive standard or heparin-containing infusates. 3 of 23 (13%) of the patients receiving heparin had catheters removed because they became functionally occluded compared to 15 of 26 (58%) in the control group (p less than 0.005). 4 of 13 (31%) single injection aortograms obtained in control infants demonstrated thrombi, compared to none of 7 in the heparin group. 1 patient in the heparin group had an aortic clot demonstrated at post-mortum examination. There were neither clinical coagulopathies nor abnormalities of partial thromboplastin time attributable to the administration of heparinized fluids. Heparinization of UAC infusates appears to be a safe method of reducing the risk of catheter occlusion. Heparin effect on large vessel clot risk remains unproven.
Effect of heparin infusates in umbilical arterial catheters on frequency of thrombotic complications.
We studied 111 infants requiring an umbilical artery catheter, 59 with heparin and 52 without. Thirty-four thrombi were detected, 16 in the heparin group and 18 in the control group. The numbers of thrombi in the two groups was not significantly different, but the number of clotted or nonfunctioning umbilical artery catheters was greater in the control group (P less than 0.05), as was the incidence of hypertension (P less than 0.05). There were no other significant differences between the two groups. We conclude that the use of low doses of heparin may not change the incidence of umbilical artery catheter-related thrombi, but it does appear to lower the incidence of their sequelae.
Effect of heparinization of fluids infused through an umbilical artery catheter on catheter patency and frequency of complications.
Heparinization of fluids (1 unit/ml) infused through an umbilical artery catheter (UAC) was efficacious in prolonging catheter patency in a double-blind, randomized, controlled clinical study. On the basis of life-table analysis, the half-life of catheter function was seven days in the heparinized group as compared with just over two days in the nonheparinized group (P less than .01). UAC occlusion occurred in 4 of 32 patients in the heparinized and 19 of 30 in the nonheparinized group (chi 2 = 17.6, P less than .01). Blood transfusions, number of arterial blood gases drawn through the UACs, and fluid infusion rates were not related to catheter occlusion. Heparinization of the UAC infusion did not alter the partial thromboplastin time or the incidence of catheter-related thromboembolic phenomena in the extremities. Heparinization of fluids infused through a UAC appears to be useful in the care of critically ill neonates.
Options:
A: Heparinization of the infusate decreases the incidence of catheter occlusion and aortic thrombosis, and reduces the frequency of intraventricular hemorrhage.
B: Heparinization of the infusate decreases the incidence of catheter occlusion but does not affect the frequency of aortic thrombosis, intraventricular hemorrhage, or other clinical outcomes.
C: Heparinization of the infusate increases the incidence of catheter occlusion and aortic thrombosis, and increases the frequency of intraventricular hemorrhage.
D: Heparinization of the infusate has no effect on the incidence of catheter occlusion, aortic thrombosis, or other clinical outcomes.
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B
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41
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the impact of using end hole umbilical arterial catheters compared to side hole catheters in newborn infants? Please answer this question based on the information provided below:
Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position.
Seventy-one sick newborn infants, who had an umbilical artery catheterized, were randomized in one of four catheter groups: long end-hole-, short end-hole-, long side-hole- or short side-hole catheter. A long catheter means a high position of the catheter tip (Th6--11) and a short catheter a low position of the tip (L3--5). An angiography through the indwelling catheter in order to diagnose thrombosis was performed before the catheter was withdrawn. Dissection of the aorta and its brances was performed on infants who died. The total frequency of thromboses was 26%. There were no thromboses among infants with long end-hole catheters while infants with short end-hole catheters had thrombosis in 26%, long side-hole catheters in 33% and short side-hole catheters in 64%. Long end-hole catheters functioned better than the others. Only 6 of 16 infants with thrombosis had physical signs from the legs, while 12 infants without thrombosis had similar signs.
Options:
A: End hole catheters are associated with a much decreased risk of aortic thrombosis.
B: Side hole catheters are associated with a much decreased risk of aortic thrombosis.
C: There is no significant difference in the risk of aortic thrombosis between end hole and side hole catheters.
D: End hole catheters are associated with a higher risk of ischemic events compared to side hole catheters.
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A
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42
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What are the clinical outcomes of prophylactic intratracheal administration of natural surfactant extract in preterm newborns at risk for developing respiratory distress syndrome? Please answer this question based on the information provided below:
Prophylaxis of respiratory distress syndrome by treatment with modified porcine surfactant at birth: a multicentre prospective randomized trial.
The objective of this prospective, multicentre trial, carried out at 18 third level hospitals in Italy, was to evaluate efficacy of modified porcine surfactant (Curosurf), administered at birth to prevent the development of respiratory distress syndrome (RDS) in premature infants. 287 babies with a gestational age of 24-30 weeks were randomized to prophylactic treatment with Curosurf (80 mg/ml; dose 20 mg/kg) or to a control group receiving no surfactant treatment in the delivery-room. Babies in both groups were eligible for rescue treatment with surfactant (200 mg/kg) if they developed clinical symptoms of RDS and required mechanical ventilation. The main end-point was to obtain, in the prophylaxis group, a 30% reduction in the incidence of grade 3-4 RDS. Median gestational age was 28 weeks in both groups and mean birth weight 1010 and 1002 g, respectively for prophylaxis and control babies. There was a 32% reduction in the incidence of grade 3-4 RDS in the prophylaxis group (p < 0.05). This was associated with a significant reduction in mean maximum fraction of inspired oxygen (0.57 vs 0.66%; p < 0.01), a decreased incidence of pulmonary interstitial emphysema (7 vs 14%; p < 0.05) and a lowered mortality (21 vs 35%; p < 0.01). Combined unfavourable outcome (mortality + bronchopulmonary dysplasia and/or grade 3-4 intraventricular hemorrhage and/or grade 2-4 retinopathy of prematurity) was significantly lower in the prophylaxis than in the second group (41 vs 58%; p < 0.01). The favourable effects of prophylactic treatment were equally recorded in all the age groups, including the babies with the lowest gestational age (24-25 weeks). Multiple and logistic regression analysis confirmed that high gestational age and surfactant prophylaxis were, independently, associated with a lower degree of RDS (p = 0.0001 and p = 0.0008, respectively) and a lower mortality (p = 0.0001 and p = 0.0045, respectively). We conclude that prophylaxis with modified natural surfactant effectively prevents RDS in newborn babies between 24 and 30 weeks' gestation.
Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.
The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.
With a randomized clinical trial, the possibility was assessed that a tracheal instillation of pulmonary surfactant prior to the first breath might prevent the development of some of the signs of neonatal respiratory distress syndrome. Of the 72 infants in the trial, all born at a gestational age of less than 30 weeks, 39 received 3 or 4 mL of surfactant, prepared from the lipids extracted from calf lung lavage. The treatment resulted in a significantly improved gas exchange during the first 72 hours of life. On the average, the arterial/alveolar PO2 ratio was 0.15 higher for the treated infants, and only about half as much extra oxygen had to be supplied. The respiratory support (peak inspiratory pressure X frequency) could be lowered significantly. Pulmonary interstitial emphysema occurred in 13 of the 33 control infants, but in only three of the 39 treated infants. Six of the control infants died in the neonatal period, but only one treated infant died. It is concluded that surfactant supplementation prior to the first breath is feasible and is of value as protection against the respiratory distress syndrome and the negative effects of hypoxia and ventilatory support.
Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome.
To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)
Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.
A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.
Double-blind clinical trial of calf lung surfactant extract for the prevention of hyaline membrane disease in extremely premature infants.
A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P less than .01 to P less than .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.
Prophylactic treatment of very premature infants with human surfactant.
We undertook a randomized, controlled trial to determine whether human surfactant administered endotracheally at birth to very premature infants (gestational age, 24 to 29 weeks) would prevent the respiratory distress syndrome or reduce its severity. Thirty-one treated infants (birth weight, 938 +/- 286 g) were compared in a blinded fashion with 29 control infants (birth weight, 964 +/- 174 g). The lecithin/sphingomyelin ratio was less than 2 in all infants, and phosphatidylglycerol was not present in amniotic fluid or tracheal fluids at birth, indicating a deficiency of surfactant in the lungs. The principal dependent variables were neonatal death, the incidence of bronchopulmonary dysplasia, and the infant's requirement for respiratory support (and its complications). The surfactant-treated group had significantly fewer deaths than the control group (16 percent vs. 52 percent, P less than 0.001), fewer cases of bronchopulmonary dysplasia (16 percent vs. 31 percent), and significantly fewer cases of pulmonary interstitial emphysema (P less than 0.001) and pneumothorax (P less than 0.02). Prophylactic treatment with human surfactant also substantially reduced the period of neonatal intensive care. We conclude that treatment with human surfactant offers promise for improving the survival of very premature infants with a surfactant deficiency and for reducing the pulmonary sequelae of the respiratory distress syndrome.
Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group.
A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.
Options:
A: Decreased risk of pneumothorax, decreased risk of pulmonary interstitial emphysema, decreased risk of mortality, and decreased risk of bronchopulmonary dysplasia or death.
B: Increased risk of pneumothorax, increased risk of pulmonary interstitial emphysema, increased risk of mortality, and increased risk of bronchopulmonary dysplasia or death.
C: No change in the risk of pneumothorax, pulmonary interstitial emphysema, mortality, or bronchopulmonary dysplasia or death.
D: Decreased risk of intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and retinopathy of prematurity.
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A
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43
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the short-term benefits and risks of using injectable gold for treating rheumatoid arthritis? Please answer this question based on the information provided below:
A controlled trial of gold salt therapy in rheumatoid arthritis.
Gold therapy in rheumatoid arthritis. A multi-centre controlled trial conducted by the Research Sub-Committee of the Empire Rheumatism Council.
Gold salts in the treatment of rheumatoid arthritis. A double-blind study.
Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.
A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, "nitritoid" reactions, and "gold pneumonitis" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.
Options:
A: Injectable gold showed no significant benefit over placebo and had a high incidence of serious toxicity.
B: Injectable gold demonstrated a significant benefit over placebo in reducing the number of swollen joints and improving patient and physician assessments, but had a higher incidence of serious toxicity.
C: Injectable gold was found to be less effective than placebo and had no significant side effects.
D: Injectable gold showed a significant benefit over placebo with no increase in the incidence of serious toxicity.
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B
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44
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the complications associated with nasal versus oral intubation for mechanical ventilation in newborn infants? Please answer this question based on the information provided below:
Benefits of orotracheal and nasotracheal intubation in neonates requiring ventilatory assistance.
To investigate differences in orotracheal (OT) and nasotracheal (NT) intubation for ventilatory assistance, we randomly assigned 91 neonates to be intubated via either of the two routes: 46 infants were assigned to the OT group and 45 infants were assigned to the NT group. Inability to intubate the nostril in three neonates, and respiratory or cardiac instability during attempted NT intubation in three neonates, resulted in the assignment of 52 infants to the OT group and 39 infants to the NT group; patients in both groups were of comparable size, sex, and clinical problems. Initial malposition of the endotracheal tube and need to retape, reposition, or replace the tube during the mean duration of intubation of 247 +/- 42 hours for the OT group and 273 +/- 57 hours for the NT group were similar. Daily Gram stains of tracheal aspirates showed that inflammation (greater than or equal to ten polymorphonuclear cells per 400 power fields) was common (51% OT group, 53% NT group). Cultures grew potential pathogens in 37% of the patients from the OT group and 31% of the NT group. There was no difference in the clinical or radiologic incidence of pneumonia. Postextubation problems were comparable: atelectasis, 48% OT and 59% NT; stridor, 15% OT and 26% NT. OT intubation may be preferred for prolonged ventilatory assistance in neonates because of the relative ease of initial intubation.
Postextubation atelectasis-the role of oral versus nasal endotracheal tubes.
Options:
A: Nasal intubation was associated with a significantly higher rate of complications compared to oral intubation.
B: Oral intubation was associated with a significantly higher rate of complications compared to nasal intubation.
C: There were no significant differences in the rates of complications between nasal and oral intubation, although post extubation atelectasis may be more frequent after nasal intubation in very low birth weight infants.
D: Both nasal and oral intubation were associated with high rates of complications, making neither route preferable.
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C
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45
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the influence of catheter material on the frequency of ischemic events, aortic thrombosis, mortality, or necrotising enterocolitis in newborn infants? Please answer this question based on the information provided below:
Efficacy of thromboresistant umbilical artery catheters in reducing aortic thrombosis and related complications.
Previous in vitro and in vivo reports suggest that catheters constructed of polyurethane with heparin bonded to the surface (HB-PU) are less thrombogenic than catheters made of polyvinyl chloride (PVC). A randomized trial sufficiently large (power 80%) to detect a reduction in the incidence of umbilical artery (UA) catheter complications, including aortic thrombus formation, from 45% to 20% was conducted in 125 infants. The infants were monitored for complications possibly related to the use of a UA catheter, such as systemic hypertension and abnormalities of lower extremity perfusion. The presence of aortic thrombi was assessed by ultrasound study 3.5 +/- 1.2 (SD) days and 11.1 +/- 2.3 days after insertion of the catheter. The use of HB-PU umbilical catheters did not lead to a significant reduction in the incidence of complications and aortic thrombi compared with the use of PVC catheters. The lack of reduction may have been related to the prolonged duration of catheter use in both groups. A much larger study would have been required to detect a smaller, but perhaps clinically significant, reduction in catheter-associated complications.
Options:
A: Heparin bonded polyurethane catheters significantly reduced the frequency of ischemic events compared to PVC catheters.
B: There were no significant differences in clinically relevant outcomes between PVC catheters and other materials.
C: Silastic catheters were found to significantly reduce aortic thrombosis compared to PVC catheters in randomized studies.
D: The study concluded that catheter material had a significant impact on mortality rates in newborn infants.
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B
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46
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the effect of combining calcium and vitamin D compared to calcium alone or placebo in preventing bone loss in patients taking systemic corticosteroids? Please answer this question based on the information provided below:
Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup.
OBJECTIVE: To determine the efficacy and safety of vitamin D 50,000 units/week and calcium 1,000 mg/day in the prevention of corticosteroid induced osteoporosis.
METHODS: A minimized double blind, placebo controlled trial in corticosteroid treated subjects in a tertiary care university affiliated hospital. The sample was 62 subjects with polymyalgia rheumatica, temporal arteritis, asthma, vasculitis, or systemic lupus erythematosus. The primary outcome measure was the percentage change in bone mineral density (BMD) of the lumbar spine in the 2 treatment groups from baseline to 36 mo followup.
RESULTS: BMD of the lumbar spine in the vitamin D and calcium treated group decreased by a mean (SD) of 2.6% (4.1%) at 12 mo, 3.7% (4.5%) at 24 mo, and 2.2% (5.8%) at 36 mo. In the placebo group there was a decrease of 4.1% (4.1%) at 12 mo, 3.8% (5.6%) at 24 mo, and 1.5% (8.8%) at 36 mo. The observed differences between groups were not statistically significant. The difference at 36 mo was-0.693% (95% CI -5.34, 3.95).
CONCLUSION: Vitamin D and calcium may help prevent the early loss of bone seen in the lumbar spine as measured by densitometry of the lumbar spine. Longterm vitamin D and calcium in those undergoing extended therapy with corticosteroids does not appear to be beneficial.
Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial.
BACKGROUND: Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists.
OBJECTIVE: To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use.
DESIGN: 2-year randomized, double-blind, placebo-controlled trial.
SETTING: University outpatient-care facility.
PATIENTS: 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d).
INTERVENTION: Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo.
MEASUREMENTS: Bone mineral densities of the lumbar spine and femur were determined annually.
RESULTS: Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids.
CONCLUSION: Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.
Prevention of glucocorticoid-induced osteopenia: effect of oral 25-hydroxyvitamin D and calcium.
Twenty-four patients (9 M and 15 F, age range 51-82) with polymyalgia rheumatica receiving 6-methylprednisolone for a period of 9 months (16 mg/daily/two weeks, 14 mg/daily/two weeks, 12 mg/daily/1 month, 10 mg/daily/1 month, 8 mg/daily/1 month, 6 mg/daily/1 month and 4 mg/daily for the last four months) were randomly assigned to receive either 250HD3 (35 mcg/day for 25 days/month) (Group A) or placebo (Group B) in a double-blind study. All patients also received 500 mg elemental calcium daily. Before and at 3, 6 and 9 months ESR, tenderness on palpation and subjective pain were evaluated. At the same times, mineral metabolism parameters (serum calcium, phosphorus, alkaline phosphatase, 24-h urinary calcium, phosphate and 24-h hydroxyproline excretion) and radial bone mineral content (BMC) were evaluated. Activity indexes (ESR and clinical parameters) improved in both groups. Furthermore, serum alkaline phosphatase and 24-h hydroxyproline excretion decreased significantly only in Group A, and BMC decreased significantly in Group B but rose slightly in Group A. No side effects were observed in any of the patients.
Effect of oral 1,25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases.
Twenty-three rheumatic disease patients with glucocorticoid-induced osteopenia (defined by measurement of forearm bone mass) completed an 18-month double-blind, randomized study to assess the effect of oral calcium and 1,25-dihydroxyvitamin D (1,25-OH2D) or calcium and placebo on bone and mineral metabolism. Intestinal 47Ca absorption was increased (P less than 0.05) and serum parathyroid hormone levels were suppressed (P less than 0.01) by 1,25-OH2D (mean dose 0.4 micrograms/day); however, no significant gain in forearm bone mass occurred, and bone fractures were frequent in both groups. In the 1,25-OH2D group, histomorphometric analysis of iliac crest biopsy specimens demonstrated a decrease in osteoclasts/mm2 of trabecular bone (P less than 0.05) and parameters of osteoblastic activity (P less than 0.05), indicating that 1,25-OH2D reduced both bone resorption and formation. We conclude that 1,25-OH2D should not be used for treatment of glucocorticoid-induced osteopenia. Since patients receiving calcium and placebo did not exhibit a loss of forearm bone mass, elemental calcium supplementation of 500 mg daily might be useful to maintain skeletal mass in patients receiving long-term glucocorticord therapy.
Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin.
BACKGROUND: Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin.
METHODS: One hundred three patients starting long-term corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year.
RESULTS: Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, -0.2 and -1.3 percent per year, respectively) than calcium alone (-4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (-2.3 percent per year). The calcitriol group also lost lumbar bone (-3.6 percent per year) but received more corticosteroid in the second year than the other two groups.
CONCLUSIONS: Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.
Options:
A: There was no significant difference in bone mineral density at any site.
B: There was a significant prevention of bone loss at the lumbar spine and forearm.
C: There was a significant increase in femoral neck bone mass and a reduction in fracture incidence.
D: There was a significant difference in biochemical markers of bone resorption.
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B
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47
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the comparative efficacies of intravenous Iloprost, oral Iloprost, and oral Cisaprost in the treatment of Raynaud's phenomenon secondary to scleroderma? Please answer this question based on the information provided below:
Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.
OBJECTIVE: To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome.
METHODS: The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later.
RESULTS: Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24).
CONCLUSION: Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.
Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon.
Iloprost is a chemically stable analog of prostaglandin I2 showing the same properties as the naturally occurring substance, but with advantages of ease of handling and administration to patients. A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy; thermography was used as one form of assessment. Our results, while showing improvements in frequency of Raynaud's attacks after iloprost compared with placebo, show no significant effects on other variables.
A randomised, double-blind study of cicaprost, an oral prostacyclin analogue, in the treatment of Raynaud's phenomenon secondary to systemic sclerosis.
Cicaprost is a new synthetic prostacylin analogue which is metabolically stable and bioavailable after oral administration; in previous studies it has been shown to have vasodilator antiplatelet effects. In this pilot study, we investigated the clinical efficacy of and patient tolerance to two dosage levels of cicaprost (2.5 micrograms tds and 5 micrograms tds) in the treatment of Raynaud's phenomenon secondary to systemic sclerosis (SSc). This was a three centre, double-blind, placebo controlled study of 49 patients carried out over four winter months. For a period of 10 days, 16 patients were given a placebo, 16 received cicaprost 2.5 micrograms tds and 17 received cicaprost 5 micrograms tds. Response was assessed based on the total number and duration of Raynaud's attacks, the average severity of the attacks, the number of painful attacks as a proportion of all attacks, a digital ulcer count, and the patients' opinion of the treatment. Although the clinical and laboratory parameters of digital vasospasm did not show statistically significant improvement in those who received cicaprost compared with those on the placebo, the severity of attacks lessened in the patients who received cicaprost 5 micrograms tds, and a statistically significant difference was seen in the average severity at week 2 post-treatment (p = 0.02). The apparent lack of overall significance was probably related to the short treatment period and relatively low doses of cicaprost used in this exploratory study. Longer studies with dose titration are probably needed to demonstrate the beneficial effects, if any, of cicaprost in patients with Raynaud's secondary to SSc, and these are being planned.
Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis.
Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.
Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.
OBJECTIVE: We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.
METHODS: Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks.
RESULTS: Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion.
CONCLUSION: Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.
Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.
OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis.
DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study.
SETTING: University medical centers.
PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years.
INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo.
MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing.
RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo.
CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.
Successful treatment of Raynaud's syndrome with Iloprost, a chemically stable prostacyclin analogue.
Twelve female patients with severe secondary Raynaud's phenomenon were treated in a randomized order with both placebo and Iloprost infusions. Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min. A 6-week follow-up period was used between the two sets of infusions. A significant number of patients reported Iloprost had improved Raynaud's symptomatology compared with placebo and this effect lasted for up to 6 weeks. The number of attacks of Raynaud's as recorded by patients in diary books was similarly reduced after Iloprost. Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost, but not after placebo infusions. Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud's syndrome.
Options:
A: Intravenous Iloprost is effective, oral Iloprost is less effective, and oral Cisaprost has minimal or no efficacy.
B: Intravenous Iloprost is ineffective, oral Iloprost is effective, and oral Cisaprost has high efficacy.
C: Both intravenous and oral Iloprost are equally effective, while oral Cisaprost has minimal or no efficacy.
D: Intravenous Iloprost and oral Cisaprost are effective, while oral Iloprost has minimal or no efficacy.
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A
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48
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the efficacy and side effects of ketanserin in the treatment of Raynaud's phenomenon in patients with scleroderma? Please answer this question based on the information provided below:
[Treatment of systemic scleroderma with ketanserin. Randomized, double-blind 6-months study of 27 cases].
Twenty-seven patients with systemic scleroderma and Raynaud's phenomenon underwent a randomised double blind therapeutic trial: monotherapy with Ketanserine (80 mg/day for 6 months) against Placebo. The secondary effects were comparable in both groups as were the withdrawals from the trial for aggravation of Raynaud's phenomenon (one in each group). No significant difference was observed between the two groups as regards the evolution of the Raynaud's phenomenon or skin changes. Dysphagia was improved in the Ketanserine group (p less than 0.05) but not in the Placebo group. Some patients in the Ketanserine group experienced an improvement in the Raynaud's phenomenon at the end of the trial period; there were no improvements in the Placebo group. Three haemorrheological parameters (total blood viscosity, plasma viscosity and thixotropism) were abnormal at the beginning of the trial and did not improve by the end in the Ketanserine group. The K infinity coefficient of Quemada's law was normal at the start of the trial and increased after treatment (p less than 0.05).
Ketanserin versus nifedipine in secondary Raynaud's phenomenon.
Effect of ketanserin on Raynaud's phenomenon in progressive systemic sclerosis: a double-blind trial.
Ketanserin was used in a randomized double-blind trial in 15 patients with Raynaud's phenomenon in progressive systemic sclerosis (PSS). Its effect on Raynaud's phenomenon was evaluated by IR-radiometry, Doppler ultrasound, nailfold capillaroscopy, frequency of finger ulcerations and patient complaints before and after a 3-month course of treatment with oral ketanserin in the dosage of 60 mg daily in the first month and 120 mg in the second and third months. Of the 8 patients treated with ketanserin, 5 showed improvement. In the other 2 patients with progression of skin sclerosis and multiorgan involvement, the peripheral vascular disorder was unchanged. Ketanserin treatment was discontinued in one patient owing to dizziness and anxiety. In one patient ketanserin was reduced to 60 mg daily because of fluid retention. There were no other adverse effects. In 7 control patients on placebo there was no significant improvement in Raynaud's phenomenon. Ketanserin, a selective, specific and pure antagonist of 5-hydroxytryptamine (serotonin) appears to be an effective agent in the treatment of Raynaud's phenomenon and digital ischaemic ulcers in PSS. Moreover, ketanserin could contribute to the understanding of the role of 5-hydroxytryptamine in PSS pathogenesis.
Ketanserin in the treatment of systemic sclerosis: a double-blind controlled trial.
In a randomized, double-blind study, the selective and specific S2-serotonergic receptor antagonist, ketanserin was compared with placebo in 24 patients with systemic sclerosis. Following a 6-week placebo washout period, patients were randomly allocated to receive ketanserin or placebo for 6 months. Ketanserin failed to produce a greater improvement than placebo in functional and objective clinical signs and symptoms as well as in most subjective assessments. However, in a global rating by the physician ketanserin was superior to placebo. No difference in the frequency or severity of side-effects was found. The results cast doubt on the hypothesis that serotonin may be a major contributing factor in the pathophysiology of systemic sclerosis.
The effectiveness of ketanserin in patients with primary Raynaud's phenomenon. A randomized, double blind, placebo controlled study.
In 41 patients with Primary Raynaud's Phenomenon (PRP) the effectiveness of the serotonin receptor blocker ketanserin has been studied in a double blind cross-over study. Subjective assessments included: frequency and duration of the attacks (both per se and combined to a severity score), cold sensation, numbness, paresthesia, pain, cold water and cold weather provocation and the appearance of spontaneous attacks. The objective measurements comprised Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar arteries. All measurements were performed both at room temperature and after instant cold provocation. The severity score, the occurrence of numbness and paresthesia and cold weather provocation improved significantly on ketanserin treatment. All objective measurements with the exception of the end-diastolic blood flow velocity of DOSA did not show significant improvements. Neither blood chemistry nor systemic blood pressure showed any significant change during ketanserin treatment. However, in the 6 (15%) patients with hypertension both systolic and diastolic blood pressure normalized. Although in objective measurements hardly any significant effects of ketanserin could be demonstrated, the results of the study suggest that orally administered ketanserin is effective for minimizing subjective complaints in patients with PRP. Ketanserin did not show any side effects.
Options:
A: Ketanserin significantly reduced the frequency and severity of Raynaud's phenomenon attacks without any notable side effects.
B: Ketanserin showed no significant difference from placebo in the treatment of Raynaud's phenomenon, except for a decrease in the duration of attacks and more subjects reporting improvement, but it was associated with more side effects.
C: Ketanserin was significantly more effective than placebo in reducing both the frequency and severity of Raynaud's phenomenon attacks, with no significant increase in side effects.
D: Ketanserin had no effect on the frequency, severity, or duration of Raynaud's phenomenon attacks and had no significant side effects.
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B
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49
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness and safety of Cyclofenil compared to placebo for treating Raynaud's phenomenon in patients with scleroderma? Please answer this question based on the information provided below:
Cyclofenil versus placebo in progressive systemic sclerosis. A one-year double-blind crossover study of 27 patients.
Cyclofenil was evaluated versus placebo in the treatment of progressive systemic sclerosis (PSS, scleroderma) in a 2 x 6-month double-blind crossover study. The mean duration of disease was six years. Of 38 patients entering the study, 27 completed both periods. Reasons for drop-outs were very high liver transaminases in three cases, cardiac death in two, and drug allergy, alcoholic problems, suspected congestive heart failure, reactivation of tuberculosis, arteriosclerotic heart disease, and lethal progression of PSS in one case each. No fatality was attributed to cyclofenil. Liver enzyme abnormalities were seen in 13 of 35 active drug periods and in 5 of 30 placebo periods. Cutaneous and visceral involvement were assessed by a large battery of subjective parameters and objective tests. Overall improvement was seen during 17 drug periods and nine placebo periods (N.S.), but a paired comparison of the status at the end of each treatment period resulted in the following distribution: 15 were improved at the end of the drug period, four at the end of placebo period (p less than 0.01) and eight were unchanged. In patients with a disease duration of five years or less, joint stiffness and pain were less on drug than on placebo treatment (p less than 0.05). In the whole group, oesophageal peristalsis improved (p less than 0.05). Blood folate increased (p less than 0.01). Working capacity was lower after the drug period than after the placebo period (p less than 0.05). Several other parameters, however, did not change significantly. Cyclofenil appears to be a promising drug in the treatment of PSS and should be tested further in controlled long-term studies.
Options:
A: Cyclofenil showed significant improvement in symptoms with no increase in dropouts compared to placebo.
B: Cyclofenil demonstrated a trend towards improvement but had more dropouts, with no statistically significant differences compared to placebo.
C: Cyclofenil was found to be highly effective and had fewer dropouts compared to placebo.
D: Cyclofenil showed no improvement and had significantly more adverse effects compared to placebo.
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B
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50
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness and side effects of prazosin in the treatment of Raynaud's phenomenon in patients with scleroderma? Please answer this question based on the information provided below:
Prazosin treatment of Raynaud's phenomenon: a double blind single crossover study.
The efficacy of prazosin (Minipress) for the treatment of Raynaud's phenomenon (RP) was assessed by patient diary data and by objective measurements of digital vessel patency before and after cold challenge. Nine of the 14 patients with complete data reported fewer RP episodes during the 2 weeks in which they received prazosin than with placebo. Eight of 9 patients in Group 1 (systemic lupus erythematosus, mixed connective tissue disease or idiopathic RP) reported improvement during prazosin therapy (p less than 0.05) while only one of 5 patients with progressive systemic sclerosis (PSS, Group 2) reported benefit. Objective measurements indicated a significant decrease (p less than 0.02) in digital artery resistance with prazosin only in Group 1. These data predict that prazosin may be beneficial in the treatment of RP for patients who do not also have PSS.
A double-blind study of prazosin in the treatment of Raynaud's phenomenon in scleroderma.
Nineteen patients with Raynaud's phenomenon in conjunction with progressive systemic sclerosis were given either prazosin hydrochloride (1 mg orally three times a day) or a placebo for eight weeks, after which the treatment procedure was reversed for four weeks. Prazosin was shown to be effective in reducing both the frequency and the severity of vasospasm reported by the patients.
Options:
A: Prazosin was found to be highly effective with no significant side effects.
B: Prazosin was found to be modestly effective, but side effects were common.
C: Prazosin was found to be ineffective and had no significant side effects.
D: Prazosin was found to be highly effective, but side effects were common.
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B
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51
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the short-term efficacy and toxicity of sulfasalazine in the treatment of rheumatoid arthritis? Please answer this question based on the information provided below:
Circulating cytokine levels in patients with rheumatoid arthritis: results of a double blind trial with sulphasalazine.
Interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF) alpha are pleiotropic cytokines produced predominantly by macrophages which have been implicated in the pathogenesis of rheumatoid arthritis (RA). Sulphasalazine has been shown to have disease modifying properties and to inhibit the production of cytokines in vitro. To evaluate the effect of sulphasalazine on cytokine production in vivo, serum cytokine levels were measured in a group of patients with RA entered into a randomised controlled trial. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF alpha were measured at baseline and at two monthly intervals for six months in 17 patients receiving sulphasalazine and in 22 patients treated with placebo. The two groups of patients had a similar age and sex distribution, had had RA for less than a year, had no joint erosions, and had not been treated previously with any other disease modifying drugs. In the 39 patients studied IL-1 alpha was detected (> 0.1 ng/ml) at baseline in 14 patients (median 0.24 ng/ml), IL-1 beta in 25 patients (median 1.0 ng/ml), TNF alpha in 27 patients (median 1.2 ng/ml), and IL-6 in 33 patients (median 0.44 ng/ml). In the group treated with sulphasalazine there was a progressive and significant decline in serum IL-1 alpha, IL-1 beta, and TNF alpha levels over the six month period (median levels at six months were < 0.1, 0.12, and 0.44 ng/ml respectively). Interleukin 6 levels were significantly reduced only at the four month time point (median level of 0.23 ng/ml). These reductions were associated with improvements in clinical and laboratory measures of disease activity. In contrast patients receiving the placebo showed no changes in serum cytokine levels and no improvement in clinical and laboratory indices of disease activity. These results suggest that sulphasalazine may exert its disease modifying effect partly by suppressing cytokine production in vivo.
Sulfasalazine in early rheumatoid arthritis. The Australian Multicentre Clinical Trial Group.
One hundred and five patients with a diagnosis of early nonerosive rheumatoid arthritis (RA) were randomized to receive enteric coated sulfasalazine as Salazopyrin En-tabs or placebo for 6 months. Sixty-five patients completed this 6 month treatment period. Patients taking sulfasalazine were significantly better than those taking placebo in terms of Ritchie articular index, number of swollen and tender joints and erythrocyte sedimentation rate. The sulfasalazine group also demonstrated a significant fall in serum hyaluronic acid, IgM rheumatoid factor and C-reactive protein concentration. Side effects leading to withdrawal from treatment occurred in 14 of the sulfasalazine group and 4 of the placebo group. The most common side effects of patients taking sulfasalazine were rashes, liver function test abnormalities and gastrointestinal upsets. Our study demonstrates the efficacy of sulfasalazine in early RA.
A double-blind controlled study comparing sulphasalazine with placebo in rheumatoid factor (RF)-negative rheumatoid arthritis.
Sulfasalazine in early rheumatoid arthritis. A 48-week double-blind, prospective, placebo-controlled study.
OBJECTIVE: To investigate the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of early rheumatoid arthritis (RA).
METHODS: Eighty patients (symptomatic disease < 12 months) were randomly assigned to treatment with SSZ or placebo for 48 weeks. Clinical, laboratory, and scintigraphic data were used to determine the effects of treatment.
RESULTS: SSZ was superior to placebo in reducing the laboratory features of inflammation, the clinical parameters of disease activity, as well as the scintigraphic activity in the joints. Furthermore, fewer erosive changes developed in the joints of patients receiving active treatment, but the difference between treatment groups did not reach statistical significance.
CONCLUSION: SSZ is effective in the treatment of RA, and its onset of action is rapid. The results support the view that SSZ retards the development of joint erosions. However, like other conventional disease-modifying antirheumatic drugs, its remission-inducing ability is insufficient.
Sulphasalazine in rheumatoid arthritis: a double blind comparison of sulphasalazine with placebo and sodium aurothiomalate.
Uncontrolled studies have suggested that sulphasalazine may be an effective second line agent in rheumatoid arthritis. Sulphasalazine was therefore compared with placebo and intramuscular sodium aurothiomalate in 90 patients with active rheumatoid arthritis. After six months' treatment both sulphasalazine and sodium aurothiomalate had produced significant clinical and laboratory benefit, whereas placebo had produced no significant change in any variable. Thirteen patients stopped taking the placebo because of lack of effect whereas only two patients stopped taking sulphasalazine and one sodium aurothiomalate for this reason. The major toxicity encountered in the group treated with sulphasalazine was nausea or vomiting, or both; this may be related to slow acetylator phenotype. Sulphasalazine appears to be an effective second line agent, and further pharmacokinetic studies might prove useful in diminishing gastrointestinal side effects.
Comparison of responses to and adverse effects of graded doses of sulfasalazine in the treatment of rheumatoid arthritis.
Sulfasalazine (0, 0.5, 1, or 2 g daily in divided doses) was given to patients with definite or classical rheumatoid arthritis (RA) insufficiently controlled by a nonsteroidal antiinflammatory drug. Grip strength, Westergren sedimentation rate, and physician and patient global assessment improved in those patients given 2 g/day. Inadequate response was the primary reason for withdrawal in the groups given placebo or 0.5 g/day, while adverse reactions (mainly gastrointestinal upset or rash) accounted for most withdrawals from the groups that received 1 or 2 g/day. Although its use is limited by adverse reactions, sulfasalazine is effective in the treatment of patients with RA.
A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis.
One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.
Options:
A: Sulfasalazine showed no significant benefit over placebo for tender and swollen joint scores, pain, and ESR, and had fewer withdrawals due to adverse reactions.
B: Sulfasalazine demonstrated a statistically significant benefit over placebo for tender and swollen joint scores, pain, and ESR, but had higher withdrawals due to adverse reactions.
C: Sulfasalazine had a significant benefit over placebo for tender and swollen joint scores and pain, but no significant difference in ESR, and had fewer withdrawals due to adverse reactions.
D: Sulfasalazine showed a significant benefit over placebo for ESR only, with no significant difference in tender and swollen joint scores and pain, and had higher withdrawals due to adverse reactions.
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B
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52
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the efficacy and toxicity of hydroxychloroquine in the treatment of rheumatoid arthritis (RA) based on a review of randomized controlled trials? Please answer this question based on the information provided below:
Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine-plus-piroxicam, and piroxicam alone.
OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients.
METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks.
RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels.
CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.
Hydroxychloroquine compared with placebo in rheumatoid arthritis. A randomized controlled trial.
OBJECTIVE: To assess the efficacy of hydroxychloroquine, 400 mg daily, for rheumatoid arthritis.
DESIGN: Six-month, double-blind, randomized trial.
SETTING: Ambulatory referral clinic in a Mexico City, Mexico, teaching hospital.
PATIENTS: A total of 126 patients with early rheumatoid arthritis were randomly assigned to receive hydroxychloroquine, 400 mg/d, or placebo; 121 patients completed the study.
RESULTS: Hydroxychloroquine showed a clinically and statistically significant improvement over placebo in joint score (20% greater mean improvement; 10% more patients improved by > 50%); pain (40% greater mean improvement; 19% more patients improved by > 50%); grip strength (22% greater mean improvement; 21% more patients improved by > 50%); patient global assessment (16% more patients stated they had improved); and physician global assessment (12% more patients were judged to have improved). Side effects were mild, and no patients in the hydroxychloroquine group required discontinuation of therapy. Patient compliance with the study medication was high.
CONCLUSION: Hydroxychloroquine is moderately effective in early rheumatoid arthritis.
Should disease-modifying agents be used in mild rheumatoid arthritis?
A 12-month double-blind controlled study comparing hydroxychloroquine 400 mg daily with placebo in 104 patients with mild RA was conducted to see whether patients with mild rheumatoid arthritis (RA) benefit from treatment with disease-modifying agents. Mild RA was defined as synovitis limited to the hands and feet, an ESR less than 30 mm/h and C-reactive protein less than 20 mg/l, a situation where accepted clinical practice is to use a non-steroidal anti-inflammatory agent alone. By 6 months, the improvement of clinical and laboratory parameters in the hydroxychloroquine treated patients was significant compared with pretreatment levels and significantly greater than the control group. This improvement was maintained at 12 months. In addition, fewer patients withdrew through lack of efficacy, eight on hydroxychloroquine versus 18 on placebo. The implications of treating this well defined group of patients is discussed.
A randomized trial of hydroxychloroquine in early rheumatoid arthritis: the HERA Study.
PURPOSE: Studies of the efficacy of hydroxychloroquine in rheumatoid arthritis have had methodological flaws and have failed to produce definitive results. The benefits and toxicity of hydroxychloroquine sulfate in 120 patients with rheumatoid arthritis of less than 2 years duration are assessed.
PATIENTS AND METHODS: A 36-week randomized double-blind, placebo-controlled trial was conducted at two university centers and four community rheumatology private practices. Patients had to have had their disease for less than 2 years and to have never received a second-line drug. Patients were randomly assigned to receive hydroxychloroquine or an equivalent number of placebo tablets in a dose of up to 7 mg/kg per day (maximum 400 mg/day). The initial dose was half the maximum dose and, if after 2 weeks of treatment there had been no side effects, the full dose was prescribed. There were four a priori primary outcomes: (1) a joint index composed of the tender joint count, the swollen joint count, the grip strength, and the duration of morning stiffness; (2) a pain index composed of the pain dimension of the Arthritis Impact Measurement Scales (AIMS) and the visual analog pain scale of the Health Assessment Questionnaire (HAQ); (3) a physical function index composed of the HAQ, the physical disability dimension of the AIMS, and the McMaster-Toronto Arthritis Patient Performance Disability Questionnaire; (4) the psychological function subscale of the AIMS. Secondary outcomes included adverse events, patient and physician global assessments, hematocrit, erythrocyte sedimentation rate (ESR) and corticosteroid usage. An intent-to-treat analysis assessed improvement at 36 weeks by Student's t-test and average improvement over the course of the study by analysis of variance for repeated measures.
RESULTS: Of 148 eligible patients, 120 were randomized. The characteristics of those randomized to hydroxychloroquine compared to placebo were similar at the study onset. At 36 weeks and over the course of the study there was statistically significant improvement in the joint index (P = 0.004, P = 0.034, respectively), the pain index (P = 0.007, P = 0.001, respectively), and the physical function index (P = 0.020, P = 0.011, respectively) in the group receiving hydroxychloroquine compared to the placebo group. There was no improvement in psychological function for hydroxychloroquine compared to placebo (P = 0.837 at 36 weeks, P = 0.89 over the course of the study). Among the secondary outcomes there was significant improvement only in the patient's (P = 0.01) and the outcome assessor's (P = 0.03) assessment of change and a trend towards a fewer number of intra-articular corticosteroid injections (P = 0.05) in the hydroxychloroquine-treated group. There were no important differences in the side effects between hydroxychloroquine or placebo.
CONCLUSION: Over 36 weeks, hydroxychloroquine had a significant benefit on synovitis, pain, and physical disability of recent-onset rheumatoid arthritis, but did not benefit psychological function.
Options:
A: Hydroxychloroquine showed no significant benefit over placebo and had a high toxicity profile.
B: Hydroxychloroquine demonstrated a statistically significant benefit over placebo with a moderate effect and low toxicity profile.
C: Hydroxychloroquine was found to be highly effective with significant toxicity concerns.
D: Hydroxychloroquine showed a significant benefit over placebo but had a high rate of withdrawals due to toxicity.
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B
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53
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the use of thyroid hormone therapy in preterm infants without congenital hypothyroidism in terms of neonatal mortality, neurodevelopmental outcomes, and respiratory distress syndrome? Please answer this question based on the information provided below:
Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant.
Improvements in the management of respiratory distress syndrome (RDS) include pre- and postnatal stimulation of pulmonary maturity, and triiodothyronine (T3) is believed to influence directly surfactant production. Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism. While a state of hypotriiodothyroninemia exists at birth, we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks' gestation. Fifty preterm infants with RDS were studied (mean gestational age 30.4 +/- 1.2 weeks and birth weight 1,180 +/- 220 g). They were at random assigned to treatment with 50 micrograms L-T3 (Thyrotardin) or to the control group. Mortality rate, peak oxygen concentrations, duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS. We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg (p less than 0.05). These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation.
Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.
The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.
Postnatal thyroxine supplementation in infants less than 32 weeks' gestation: effects on pulmonary morbidity.
OBJECTIVE: Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes. We designed this study to evaluate the effects of early thyroxine (T4) administration in the premature infant.
STUDY DESIGN: A total of 49 newborns less than 32 weeks' gestation, were randomized in a double-blind, placebo-controlled trial. Within the first 48 hours of life, T4 (10 or 20 micrograms/kg; intravenous or through nasogastric tube, respectively) was administered for a total of 21 days. Chronic lung disease, the primary outcome variable, was defined by oxygen dependency at 28 days of life.
RESULTS: The incidence of chronic lung disease, death, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, and sepsis was not different in the placebo and treated groups.
CONCLUSION: Early T4 supplementation in preterm newborns less than 32 weeks' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity.
Neonatal thyroxine supplementation in very preterm children: developmental outcome evaluated at early school age.
OBJECTIVE: Transient hypothyroxinemia in very premature infants is associated with developmental problems. A randomized, placebo-controlled trial of thyroxine (T(4)) supplementation was conducted in a group of 200 infants <30 weeks' gestation. T(4) supplementation improved mental outcome at 2 years old in children of 25/26 weeks' gestation only. The effect of T(4) supplementation beyond 2 years of age is unknown. We present the effects of neonatal T(4) supplementation on outcome at early school age.
METHODS: Standardized measurements were used to assess cognitive, behavioral, and motor outcome, as well as a qualitative assessment of neurologic functioning. Survivors of the T(4) trial were assessed at the age of 5.7 years.
RESULTS: Ninety-nine percent of the 157 survivors participated. Outcome on all domains was comparable between the T(4) group and placebo group. In children <27 weeks' gestation, a 10 IQ point difference was found in favor of the T(4) group, whereas in children of 29 weeks' gestation, a difference of 15 IQ points was found in favor of the placebo group. Teachers' reports showed less behavioral problems in the T(4)-treated children of 25/26 weeks' gestation, but more behavioral problems in the T(4)-treated children of 27 weeks' gestation. Differences in motor outcome and neurologic outcome were in favor of the T(4)-treated children <29 weeks' gestation, but not of the T(4)-treated children of 29 weeks' gestation.
CONCLUSIONS: We found benefits of T(4) supplementation for children <29 weeks' gestation, and especially in children of 25/26 weeks' gestation. However, in children of 29 weeks' gestation T(4) supplementation is associated with more developmental problems.
Evaluation of the effect of thyroxine supplementation on behavioural outcome in very preterm infants.
Two-hundred infants of <30 weeks gestational age were included in a randomized double-blind controlled trial to study the effect of thyroxine administration on neurodevelopmental outcome in very preterm children. The infants were given either a fixed dose of thyroxine (8 microg/kg birthweight/day) or placebo for the first 6 weeks of life. This paper evaluates the effect of thyroxine administration on behavioural outcome at the age of 2 years. More externalizing, especially destructive, behaviours were found in the group given thyroxine than in the placebo group. This difference was more pronounced in boys and in children born after 27 weeks' gestation. The thyroxine-treated children with behavioural problems had lower plasma-free thyroxine levels than the thyroxine-treated children without behavioural problems. This finding suggests that the presence of more behavioural problems in the group given thyroxine was not an immediate consequence of the treatment.
Somatosensory evoked potentials in very preterm infants in relation to L-thyroxine supplementation.
OBJECTIVE: To study the effect of L-thyroxine supplementation on neurologic maturation in very preterm infants with transient hypothyroxinemia.
DESIGN: Randomized, double-blind, placebo-controlled, L-thyroxine supplementation trial.
SETTING: Level III neonatal intensive care unit.
SUBJECTS: A total of 200 infants <30 weeks' gestational age.
INTERVENTION: Subjects were randomly assigned to receive L-thyroxine (8 microg/kg birth weight per day) or a placebo during the first 6 weeks of life.
METHODS: Median nerve somatosensory evoked potentials were recorded, measuring cortical N1 peak latency at 2 weeks of age, at term, and at 6 months (corrected) age.
RESULTS: Cortical N1 peak latency was not decreased significantly in the L-thyroxine group compared with the placebo group throughout the study period.
CONCLUSION: L-Thyroxine supplementation during the first 6 weeks of life did not decrease cortical N1 peak latency in infants of <30 weeks' gestational age.
Motor nerve conduction velocity in very preterm infants in relation to L-thyroxine supplementation.
BACKGROUND: Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity. It is still unknown whether L-thyroxine supplementation is required. During an L-thyroxine supplementation trial, motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity.
METHODS: Two hundred infants < 30 weeks' gestational age were enrolled in a randomized, double-blind, placebo-controlled L-thyroxine supplementation trial. L-Thyroxine (8 micrograms/kg birthweight per day) or a placebo was administered during the first 6 weeks of life. Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth, at 2 weeks, at 40 weeks, and at 66 weeks postmenstrual age.
RESULTS: At 2 weeks, the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group, although the difference was not statistically significant (difference between means: 0.8 msec; 95% CI: -0.13 to 1.80; p = 0.06). Later on, no effect of L-thyroxine supplementation on motor nerve conduction velocity was found.
CONCLUSION: This study shows that in infants < 30 weeks' gestational age L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity.
Thyroid function in very preterm newborns: possible implications.
Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low thyroxine (T4) and free thyroxine (FT4) values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomized, double-blind, placebo-controlled trial with T4 in 200 infants less than 30 weeks gestation. T4 (or placebo) was given in fixed dose of 8 microg/kg birth weight per day during the first 6 weeks after birth. It resulted in a significant increase of T4, FT4, and reverse triiodothyronine (rT3). Thyrotropin (TSH) secretion was suppressed, and, probably as a result of TSH suppression, triodothyronine (T3) levels were decreased in the T4 group. Mortality was 14% in the T4 group and 21% in the placebo group (NS). No effect was found on morbidity. Heart rate was significantly higher in T4-treated infants less than 28 weeks gestation, but not in T4-treated infants 28 weeks or more, who had the highest FT4 levels. In the study groups as a whole, no clear effect of T4 administration was found on neurodevelopmental outcome. However, there was a strong trend toward improvement of adverse outcome, defined as death or abnormal developmental outcome at 2 years of age. In addition, mental outcome in a subgroup of T4-treated infants less than 27 weeks' gestation was significantly better than in placebo infants of the same age group. In conclusion, this trial does not clearly have conclusive results. New trials of thyroid hormone treatment should be carried out in preterm infants, in order to investigate whether indeed T4 supplementation is required in preterm infants less than 27 or 28 weeks gestation. Addition of T3 to the treatment schedule needs to be considered.
Thyroid function in preterm newborns; is T4 treatment required in infants < 27 weeks' gestational age?
Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low T4 and FT4 values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomised, double-blind, placebo-controlled trial with T4 in 200 infants < 30 weeks' gestation. In the study groups as a whole (n = 100 in the T4 group, n = 100 in the Placebo group), no clear effect of T4 administration was found. In this study we examined whether gestational age influenced the effect of T4 administration. The T4- and placebo groups were subdivided into 4 groups according to gestational age. FT4-values during the first weeks after birth were lowest in the youngest gestational age group in the T4 as well as in the placebo group. In this group with infants < 27 weeks' gestation mental developmental outcome at 2 years of age was significantly better than in the placebo group of the same gestational age. There was also a trend towards a better psychomotor and neurological outcome. Beyond 27 weeks' gestation, no clear effect of T4 could be found; on the contrary, a possible harmful effect on mental developmental outcome might be the result. In conclusion. T4 treatment possibly improves developmental outcome in infants < 27 weeks' gestation, but seems not necessary beyond this gestational age.
Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations.
OBJECTIVE: To investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants.
DESIGN AND METHODS: Two hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T4) (at a fixed daily dose of 8 microg/kg birthweight) or placebo was started 12-24h after birth and discontinued 6 weeks later. Plasma concentrations of T4, tri-iodothyronine (T3), reverse T3 (rT3), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter.
RESULTS: The T4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T4 and rT3 were significantly increased in the T4 group. TSH concentrations were depressed in the T4 group and T3 was significantly decreased, probably as a result of TSH depression. The T4/T3 and T4/rT3 ratios differed significantly between the two study groups.
CONCLUSIONS: Daily T4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T4 and T3.
Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation.
BACKGROUND: Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction. Whether thyroxine treatment during this period results in improved developmental outcomes is not known.
METHODS: We carried out a randomized, placebo-controlled, double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks' gestation. Thyroxine (8 microg per kilogram of birth weight) or placebo was administered daily, starting 12 to 24 hours after birth, for six weeks. Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth. Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6, 12, and 24 months of age (corrected for prematurity).
RESULTS: Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups. At 24 months of age, 157 infants were evaluated. Overall, neither mental nor psychomotor scores differed significantly between the study groups at any time, nor was the frequency of abnormal neurologic outcome significantly different. In thyroxine-treated infants born at gestational ages of less than 27 weeks, the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group (P=0.01); for thyroxine-treated infants born at 27 weeks or later, the mental-development score was 10 points lower than that of their counterparts in the placebo group (P=0.03). There was no relation between the initial plasma free thyroxine concentration and the effect of treatment.
CONCLUSIONS: In infants born before 30 weeks' gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.
Thyroid function in very preterm infants: influences of gestational age and disease.
It is not known how immaturity and disease influence postnatal thyroid function in infants <30 wk of gestational age. We performed serial measurements of plasma thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), TSH, and T4-binding globulin (TBG) in 100 infants of <30 wk of gestation, during the first 8 postnatal weeks, to investigate the influences of disease and gestational age on the time course of thyroid hormones. One hundred infants were divided twice into two groups: 1) in a group of 25-28 and of 28-30 wk of gestation; and 2) in a sick and a healthy group, with similar gestational ages. The time course of T4, FT4, T3, TSH, and TBG, but not rT3 differed significantly (p < 0.005) between the gestational age groups. T4 and FT4 decreased to levels below the cord blood value with a deeper FT4 nadir on d 7 in the youngest group. Disease decreased T4, FT4, T3, TSH, and TBG concentrations especially during the 1st wk after birth (p < 0.005). However, the FT4 nadir on d 7 was similar in sick and healthy infants. After 3 wk, T4, FT4, T3, and TBG were higher in the sick group compared with the healthy group. rT3 levels were not increased in sick infants. We conclude that the extent of the FT4 decrease after birth in infants of <30 wk gestation is mainly influenced by gestational age and probably reflects a transient depletion of thyroidal hormone reserves. rT3 cannot be used as a marker of nonthyroidal illness in very preterm infants.
L-thyroxine treatment of preterm newborns: clinical and endocrine effects.
Preterm newborns have low serum thyroxine (T4) levels compared with late-gestational fetuses. Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction. We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age <31 wk. Forty newborns were randomized in a double blind protocol: 20 infants received a daily dose of 20 microg/kg L-T4 for 2 wk, whereas 20 control infants received saline. Serum concentrations of T4, triiodothyronine (T3), reverse T3 (rT3), thyroglobulin (TG), and TSH were measured weekly as well as serum levels of GH, prolactin, and IGF-I. After 2 wk, a TSH-releasing hormone (TRH) test was performed. Neonatal illness and outcome was evaluated by noting heart rate, oxygen requirement, duration of ventilation, development of chronic lung disease, oral fluid intake, and weight gain; a Bayley score was done at the corrected age of 7 mo. L-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels, whereas the postnatal decline in serum rT3 was more gradual. L-T4 treatment was associated with a decrease in serum TG and TSH levels. TRH injection induced a definite rise in serum TSH and T3 in controls, but not in L-T4 treated newborns. Neither L-T4 treatment, nor TRH administration appeared to alter circulating levels of prolactin, GH, or IGF-I. In contrast to the pronounced endocrine effects, no clinical effects of L-T4 administration were detected.
L-thyroxine treatment of preterm newborns: clinical and endocrine effects.
Preterm newborns have low serum thyroxine (T4) levels compared with late-gestational fetuses. Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction. We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age <31 wk. Forty newborns were randomized in a double blind protocol: 20 infants received a daily dose of 20 microg/kg L-T4 for 2 wk, whereas 20 control infants received saline. Serum concentrations of T4, triiodothyronine (T3), reverse T3 (rT3), thyroglobulin (TG), and TSH were measured weekly as well as serum levels of GH, prolactin, and IGF-I. After 2 wk, a TSH-releasing hormone (TRH) test was performed. Neonatal illness and outcome was evaluated by noting heart rate, oxygen requirement, duration of ventilation, development of chronic lung disease, oral fluid intake, and weight gain; a Bayley score was done at the corrected age of 7 mo. L-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels, whereas the postnatal decline in serum rT3 was more gradual. L-T4 treatment was associated with a decrease in serum TG and TSH levels. TRH injection induced a definite rise in serum TSH and T3 in controls, but not in L-T4 treated newborns. Neither L-T4 treatment, nor TRH administration appeared to alter circulating levels of prolactin, GH, or IGF-I. In contrast to the pronounced endocrine effects, no clinical effects of L-T4 administration were detected.
Options:
A: Thyroid hormone therapy significantly reduced neonatal mortality, improved neurodevelopmental outcomes, and reduced the severity of respiratory distress syndrome.
B: Thyroid hormone therapy had no significant effect on neonatal mortality, neurodevelopmental outcomes, or the severity of respiratory distress syndrome.
C: Thyroid hormone therapy significantly reduced neonatal mortality but had no significant effect on neurodevelopmental outcomes or the severity of respiratory distress syndrome.
D: Thyroid hormone therapy had no significant effect on neonatal mortality but significantly improved neurodevelopmental outcomes and reduced the severity of respiratory distress syndrome.
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B
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54
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the short-term effects of cyclosporine in the treatment of patients with rheumatoid arthritis? Please answer this question based on the information provided below:
Cyclosporin in rheumatoid arthritis: a double blind, placebo controlled study in 52 patients.
The efficacy and safety of cyclosporin A (CyA) for patients with rheumatoid arthritis were assessed in a four month double blind, placebo controlled study using an initial dosage of 5 mg/kg daily. Six patients withdrew from the study (two in the placebo group because of inefficacy of treatment and four in the CyA group because of side effects). These six patients were considered therapeutic failures. At the end of the trial the study treatment was considered as good or very good by 14 out of the 26 CyA group patients and by only two out of the 26 placebo group patients. Moreover, in the CyA group significant improvement was observed in five of the seven clinical assessment criteria. Clinical improvement was correlated with a decrease in C reactive protein, alpha 1 glycoprotein levels, and platelet count but not with erythrocyte sedimentation rate or rheumatoid factor titres. Renal toxicity (13 cases) remained the major problem in the management of these patients. This study shows that CyA is effective in active rheumatoid arthritis but requires close monitoring for toxicity.
Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine. Results of a 48-week multicenter study comparing low-dose cyclosporine with placebo. Norwegian Arthritis Study Group.
OBJECTIVE: To evaluate the therapeutic efficacy of 46 weeks of treatment with cyclosporine (5 mg/kg/day) in patients with rheumatoid arthritis (RA).
METHODS: A 48-week randomized, double-blind, placebo-controlled, multicenter study of cyclosporine was conducted in 122 patients with active RA. Patients were evaluated by objective and subjective clinical and radiologic measurements at baseline and at the end of the study.
RESULTS: Statistically significant improvement and clinically important changes were seen for the number of tender joints, number of swollen joints, pain score, duration of morning stiffness, and Lee's functional index in the cyclosporine-treated group at the end of the study. Radiographic examination showed that cyclosporine was capable of retarding joint destruction. In the cyclosporine-treated group, serum creatinine levels increased by 17.5 mumoles/liter (23%) at week 24 and by 21.8 mumoles/liter (26%) at week 48. There was no significant difference in mean serum creatinine levels in patients treated with cyclosporine alone and those treated with cyclosporine plus nonsteroidal antiinflammatory drugs. Five patients had to be treated with antihypertensive drugs, and 2 patients were withdrawn from the study because of increased serum creatinine.
CONCLUSION: The study shows that cyclosporine seems to have disease-modifying effects in RA.
Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis.
144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.
Options:
A: Cyclosporine showed no significant difference compared to placebo in reducing the number of swollen joints.
B: Cyclosporine significantly decreased the number of tender and swollen joints and improved pain and functional index compared to placebo.
C: Cyclosporine increased the number of swollen joints and had no effect on pain and functional index compared to placebo.
D: Cyclosporine had no significant side effects and showed no clinical benefit compared to placebo.
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B
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55
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the efficacy of various pharmacological treatments for different clinical features of Behcet's syndrome? Please answer this question based on the information provided below:
A double blind study of colchicine in Behçet's disease.
[Desensitization by autologous saliva and Behçet's disease].
Among 240 patients with Behçet's disease seen in the Internal Medicine Department of the Ibnou Rochd University Hospital, Casablanca, between January 1981 and April 1988, 44 were selected to study the effects of desensitization by autologous saliva on oral and genital aphthae and on articular manifestations. Thirty of these 44 patients received gradually decreasing dilutions of their own saliva, and 14 control patients received physiological saline. Injections were administered intradermally twice a week during 15 weeks, then once a week during one year, so that the study lasted one and a half year, from October 1986 to April 1988. No improvement of the arthritis was observed, whereas the oral aphthae were improved in 50% of the patients desensitized by their own saliva. This percentage would have raised some hopes for the treatment of these sometimes disabling lesions were it not for the fact that 50% of the controls were similarly improved. This suggests that desensitization by saliva has a placebo effect.
Evaluation of conventional therapy versus cyclosporine A in Behçet's syndrome.
When ocular structures are affected in Behçet's syndrome, a rapid loss of vision has been the rule regardless of the type of treatment--corticosteroids, Leukeran, Imuran, colchicine. The objectives of the present study were to compare, in a masked manner, conventional treatment (corticosteroids/Leukeran) to treatment with CsA. Forty patients suffering from Behçet's syndrome with active ocular inflammatory reactions were included in the study. These were randomly assigned to conventional or CsA regimens and were regularly examined by a multidisciplinary group of physicians. The unmasked internist modulated the treatment and recorded systemic manifestations. The masked ophthalmologists recorded the ocular findings without knowledge of the assigned type of treatment. An analysis of the results 3 years after initiation of the study shows that CsA is more effective than conventional therapy in decreasing the active ocular inflammatory processes and arresting the deterioration of visual acuity. Regarding the extraocular symptoms, however, conventional therapy is superior to CsA, especially for the control of skin lesions and arthritis. Side effects were recorded in a much higher incidence among patients receiving CsA. However, tight and constant control of the CsA dosage as performed in this study has, so far, prevented clinical and biochemical nephrotoxic manifestations in patients assigned to this treatment.
The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behçet's disease. A randomized clinical trial.
OBJECTIVE: Because exposure to streptococcal antigens might be a major disease activity-provoking factor in Behçet's disease, this study was undertaken to evaluate the effectiveness of benzathine penicillin in the prophylaxis of recurrent arthritis episodes during the course of this disease.
METHODS: A prospective, randomized study design was used to allocate patients to receive colchicine alone or colchicine plus benzathine penicillin for 24 months.
RESULTS: The duration, severity, and pattern of arthritis episodes were found to be similar in the 2 treatment groups, but the number of arthritis episodes was significantly reduced, and the duration of episode-free time significantly prolonged, in the penicillin group compared with the colchicine-alone group.
CONCLUSION: Penicillin treatment was demonstrated to offer adjunctive benefits in the prevention of arthritis episodes which are not obtainable with colchicine monotherapy. This finding could provide additional evidence for antigen triggering in the pathogenesis of Behçet's disease.
Treatment with acyclovir does not affect orogenital ulcers in Behçet's syndrome: a randomized double-blind trial.
Acyclovir is a potent antiviral drug, of proven efficacy in the treatment of herpes simplex virus infection. Since this virus has been implicated in the aetiology of Behçet's syndrome, the effect of acyclovir on orogenital ulceration in this condition was determined in a randomized, double-blind, placebo-controlled, crossover trial. Eighteen of 22 patients entering the study completed the trial. Treatment with acyclovir failed to alleviate the frequency and severity of orogenital ulceration or other disease features.
Inefficacy of topical alpha interferon in the treatment of oral ulcers of Behçet's syndrome: a randomized, double blind trial.
Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet's disease.
The efficacy and safety of oral cyclosporin 10 mg/kg per day in Behçet's disease were compared in a randomised double-masked study with those of colchicine, 1 mg orally per day, and were also investigated in a long-term open study. The double-masked study showed that cyclosporin was effective in treating not only the ocular manifestations of Behçet's disease but also oral aphthous ulcer, dermal lesions, and genital ulceration. Efficacy did not weaken during long-term treatment.
Inefficacy of azapropazone in the acute arthritis of Behçet's syndrome: a randomized, double blind, placebo controlled study.
Sixty-three consecutive Behçet's syndrome patients with an acute arthritis of up to 10 days duration were treated either with azapropazone (APZ) 300 mg t.i.d. or placebo for three weeks. Twenty-eight patients (14 males, 14 females: mean age 36.2 +/- 8.1 SD years) from the APZ group and 29 patients (18 males, 11 females; mean age 34.2 +/- 8.4 SD years) from the placebo group completed the trial. At the end of the trial the arthritis persisted in 53.5% (15/28) of the APZ patients and in 41.3% (12/29) of the placebo patients (chi 2 = 0.85; NS). Six patients (6/28; 21%) from the APZ group and 9 patients (9/29; 31%) from the placebo group developed new joint involvement (chi 2 = 0.7; NS). There was no difference in the duration of arthritis between the two groups (19.9 +/- 8.3 SD days in the APZ groups vs. 19.7 +/- 8.2 SD days in the placebo group; NS). The degree of joint swelling, the tender joint score and the visual analogue score for pain significantly improved in both groups, but there was no difference in any of these parameters between the groups except for a significant difference in the visual analogue score for less pain at the first week in the azapropazone group (t = 2.23; p < 0.05). There were also no differences in the mean numbers of acetaminophen tablets used or in the CRP and ESR levels between the two groups. We conclude that azapropazone is not effective in controlling the arthritis of Behçet's syndrome.
Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet's syndrome: a single masked trial.
A single masked trial of cyclosporin A 5 mg/kg/day versus monthly 1 g intravenous boluses of cyclophosphamide was conducted among 23 patients with Behçet's syndrome and active, potentially reversible uveitis. The trial was unmasked after a mean of 12 (SD 2) months for the cyclosporin A group (n = 12) and a mean of 10 (SD 3) months for the cyclophosphamide group (n = 11). During the initial 6 months the visual acuity significantly improved (p < 0.001) in the cyclosporin A group whereas this was not observed in the cyclophosphamide group. The subsequent follow-up of patients up to 24 months suggested that the initial improvement in visual acuity with cyclosporin A was not sustained. More extensive and especially long-term studies of cyclosporin A in the uveitis of Behçet's syndrome are warranted.
A controlled trial of azathioprine in Behçet's syndrome.
Cytotoxic agents have long been used in Behçet's syndrome, especially for eye involvement, but their effectiveness has been uncertain. We conducted a two-year randomized, placebo-controlled, double-blind trial of azathioprine (2.5 mg per kilogram of body weight per day) in Turkish men with Behçet's syndrome without eye disease (group 1; n = 25) or with eye disease (group 2; n = 48). Corticosteroid treatment remained available to all the patients. All six patients withdrawn from the study because of severe eye disease were receiving placebo (P less than 0.001). Azathioprine was superior to placebo in the prevention of new eye disease in group 1 (1 vs. 8 patients; P less than 0.01) and in group 2 among the 14 patients who at entry had disease in only one eye (P less than 0.001). There were fewer episodes of hypopyon uveitis (1 vs. 15; P less than 0.001) among the group 2 patients who took azathioprine. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis. There were no serious side effects attributable to azathioprine. We conclude that azathioprine is effective in controlling the progression of Behçet's syndrome, especially its most serious manifestation, eye disease.
Options:
A: Colchicine, cyclophosphamide, and steroids were effective for eye involvement, while azapropazone and colchicine were effective for arthritis.
B: Cyclosporine and azathioprine were found to be protective for eye involvement, and benzathine-penicillin was effective for arthritis.
C: Acyclovir, colchicine, and topical interferon were effective for treating aphthas, and azapropazone was effective for arthritis.
D: All classic treatments, including colchicine, cyclophosphamide, and steroids, were found to be effective for all clinical features of Behcet's syndrome.
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B
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56
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the effects of intratracheal administration of synthetic surfactant in premature newborns with established respiratory distress syndrome (RDS)? Please answer this question based on the information provided below:
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.
A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.
BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants.
METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo.
RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055).
CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.
Outcome at 1-year adjusted age of 957 infants weighing more than 1250 grams with respiratory distress syndrome randomized to receive synthetic surfactant or air placebo. American and Canadian Exosurf Neonatal Study Groups.
This study determined outcomes at 12-months adjusted age of 957 infants weighing more than 1250 gm at birth who were subjects in a randomized, double-blind, controlled trial of synthetic surfactant or air placebo administered in a rescue trial at 23 hospitals in the United States and 13 hospitals in Canada. Follow-up results were available for 475 of 563 surviving infants who received air placebo (84%) and 482 of 571 infants who received synthetic surfactant (84%). Developmental outcome was equivalent in the two groups. Morbidity was less in the synthetic surfactant group as assessed by the need for medication for chronic lung disease (52 of 475 (11%) for the air placebo group vs 32 of 482 (7%) for the synthetic surfactant group) or respiratory support (10 of 475 (2%) for the air placebo group vs 1 of 482 (< 1%) for the synthetic surfactant group) at 1-year adjusted age. Bayley Scales of Infant Development (mental development Index: 102 for both the air placebo and synthetic surfactant groups; psychomotor development index: 95 for the air placebo group vs 94 for the synthetic surfactant group) and impairment rates (94 of 475 (20%) for the air placebo group vs 86 of 482 (18%) for the synthetic surfactant group) were similar in the two groups. Infants weighing more than 1250 gm who have respiratory distress syndrome have previously been shown to have improved survival rates and lower neonatal morbidity after treatment with synthetic surfactant. These follow-up data confirm that developmental outcome as determined at 12-months adjusted age is at least as good in those receiving synthetic surfactant.
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.
Effects of two rescue doses of synthetic surfactant in 344 infants with respiratory distress syndrome weighing 750 to 1249 grams: a double-blind, placebo-controlled multicenter Canadian trial. Canadian Exosurf Neonatal Study Group.
In a multicenter, double-blind, placebo-controlled rescue trial conducted at 13 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 344 infants with birth weights of 750 to 1249 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio less than 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to the infants remaining on mechanical ventilation. Infants were stratified at study entry by birth weight and gender. The trial was terminated short of the targeted sample size because significant reductions in mortality were observed in another rescue trial completed in the United States in the same weight class of infants. Despite premature termination of the trial, the rate of survival without bronchopulmonary dysplasia was increased (61% vs 52%; p = 0.046) in infants treated with surfactant. In addition, there was a significant reduction in the incidence of overall pulmonary air leak (46% vs 32%; p = 0.009), pneumothorax (27% vs 17%; p = 0.023), and pulmonary interstitial emphysema (40% vs 28%; p = 0.018) in infants treated with synthetic surfactant. There was no difference in the incidence of bronchopulmonary dysplasia, apnea, or pulmonary hemorrhage. Significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7 were present. These findings indicate that rescue therapy with synthetic surfactant can improve outcome for premature infants weighing 750 to 1249 gm with respiratory distress syndrome.
One-year outcome in 232 premature infants with birth weights of 750 to 1249 grams and respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group.
A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.
Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease.
EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial.
One-year follow-up of 89 infants with birth weights of 500 to 749 grams and respiratory distress syndrome randomized to two rescue doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group. Canadian Exosurf Neonatal Follow-Up Group.
Double-blind neurodevelopmental and physical evaluations were conducted at 1-year adjusted age in 89 infants with birth weights of 500 to 749 gm who had respiratory distress syndrome in the neonatal period and were randomized to receive two rescue doses of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) or air placebo. The trial used a common protocol and was conducted at 13 hospitals; patients were entered in the trial between February 1988 and September 1990. Ninety-five percent of surviving infants were assessed. Growth and development in the two groups were equivalent. Mean Bayley Scales of Infant Development scores were comparable (mental development index, 79 +/- 22 vs 87 +/- 20; psychomotor development index, 73 +/- 18 vs 81 +/- 19 for air placebo and synthetic surfactant, respectively). The incidence of severe retinopathy of prematurity was significantly decreased in the surfactant group compared with the air placebo group (15% vs 34%; relative risk 0.428; 95% confidence interval 0.2 to 0.9). Overall, administration of surfactant appeared to increase the probability of a favorable outcome. Confirmation of the trends observed in this study would provide a strong rationale for the rescue use of synthetic surfactant in extremely low birth weight infants with respiratory distress syndrome even if overall mortality is not reduced.
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.
Double-blind, randomized, placebo-controlled Canadian multicenter trial of two doses of synthetic surfactant or air placebo in 224 infants weighing 500 to 749 grams with respiratory distress syndrome. Canadian Exosurf Neonatal Study Group.
In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated.
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.
One-year follow-up evaluation of 260 premature infants with respiratory distress syndrome and birth weights of 700 to 1350 grams randomized to two rescue doses of synthetic surfactant or air placebo. American Exosurf Neonatal Study Group I.
A multicenter, randomized, double-blind, placebo-controlled trial of synthetic surfactant therapy for premature infants with respiratory distress syndrome (RDS) and birth weights of 700 to 1350 gm demonstrated a reduction in severity of RDS, morbidity, and neonatal and 1-year mortality. Of the 419 infants who were entered in the study, 80% of the surviving infants in both the air placebo group (122) and the synthetic surfactant group (138) returned for the follow-up evaluation at 1-year adjusted age. The only significant difference observed at follow-up was a reduction in the incidence of mild cerebral palsy in the synthetic surfactant group (air placebo group, 8 of 122 (7%); synthetic surfactant group, 3 of 138 (2%); relative risk 0.306; 95% confidence interval 0.094, 0.999). No differences were observed between the air placebo and synthetic surfactant treatment groups with respect to health status of the infants, including the incidence of retinopathy of prematurity and neurodevelopmental delays. The difference in the overall incidence of impairment among the 1-year survivors in the air placebo group (43 of 122 (35%)) and in the synthetic surfactant group (40 of 138 (29%)) was not statistically significant. The results of this 1-year follow-up study show that rescue treatment with synthetic surfactant in infants weighing 700 to 1300 gm is not associated with adverse developmental consequences despite the improvement in survival.
Effects of two rescue doses of a synthetic surfactant on mortality rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome. The American Exosurf Neonatal Study Group I.
In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.
Two controlled trials of dry artificial surfactant: early effects and later outcome in babies with surfactant deficiency.
Dry powdered surfactant was used in two randomised, controlled trials to study its immediate effects, influence on mortality, and safety in babies born after less than 32 weeks' gestation. The lecithin/sphingomyelin (L/S) ratio was measured in pharyngeal aspirate taken before surfactant therapy to establish surfactant deficiency. 32 babies intubated during resuscitation (trial I) and a group of 24 other babies, all with immature L/S ratios, in whom severe hyaline membrane disease developed (trial II), were stratified for sex. In half 25 mg surfactant was insufflated through the endotracheal tube; it could be detected in tracheal secretions for at least the next 24 h. There was no significant difference in ventilator pressures or oxygen therapy used nor in neonatal mortality and morbidity in the first 2 years of life between the surfactant-treated and control groups in either trial.
Options:
A: Improves pulmonary gas exchange and decreases the requirement for ventilatory support.
B: Increases the risk of pneumothorax and pulmonary interstitial emphysema.
C: Has no significant impact on neonatal mortality or bronchopulmonary dysplasia.
D: Increases the risk of intraventricular hemorrhage and patent ductus arteriosus.
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A
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57
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the short-term effects of cyclophosphamide in the treatment of rheumatoid arthritis as observed in clinical trials? Please answer this question based on the information provided below:
A controlled trial of cyclophosphamide in rheumatoid arthritis.
Controlled trial of cyclophosphamide in rheumatoid arthritis.
Twenty-four patients with severe progressive rheumatoid arthritis were randomly assigned to cyclophosphamide or placebo in a double-blind crossover trial. Eleven patients who completed 9 months on cyclophosphamide (average dose: 1.8 mg/kg/day) demonstrated significant decrease in painful joints, swollen joints, and morning stiffness and increase in grip strength when compared to 11 patients on placebo. After crossover, significant improvement was observed in patients switched to cyclophosphamide, and deterioration within 2 months was observed in most patients changed from drug to placebo. Serum immunoglobulins and rheumatoid factor titers decreased with cyclophosphamide but antibody response to Vi antigen was unaffected. Primary delayed immune response to 2,4-dinitrochlorobenzene was markedly depressed. Adverse effects were troublesome--hemorrhagic cystitis affected 4 patients and amenorrhea occurred in 3. Despite striking beneficial effect, cyclophosphamide should be prescribed cautiously and only in severe resistant cases of rheumatoid arthritis.
Options:
A: Cyclophosphamide showed no significant benefit over placebo in reducing tender and swollen joint scores.
B: Cyclophosphamide demonstrated a statistically significant benefit in reducing tender and swollen joint scores compared to placebo.
C: Cyclophosphamide significantly increased the erythrocyte sedimentation rate (ESR) compared to placebo.
D: Cyclophosphamide had fewer adverse reactions compared to placebo.
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B
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58
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of moderate-term, low-dose corticosteroids in the treatment of rheumatoid arthritis? Please answer this question based on the information provided below:
EMPIRE Rheumatism Council; multi-centre controlled trial comparing cortisone acetate and acetyl salicylic acid in the long-term treatment of rheumatoid arthritis; results up to one year.
Low dose prednisone therapy in rheumatoid arthritis: a double blind study.
Prednisone, 5 mg taken each morning, was added to other drugs in 18 patients with rheumatoid arthritis. Sixteen patients were given a placebo in this double blind study. After 24 weeks, all patients were given the placebo. Slight functional improvement was noted in the prednisone group during the 24-week period, but deterioration after switching to placebo was sustained for at least 8 weeks. Progression of hand erosions occurred in 1 prednisone-treated patient, and in 4 controls. An asymptomatic vertebral spine compression fracture developed in 2 patients given prednisone; this was the only toxicity noted possibly due to this therapy. Minimal dose prednisone may be useful as "bridge" therapy between nonsteroidal antiinflammatory therapy and use of disease-modifying drugs.
The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group.
BACKGROUND: Oral glucocorticoids are widely used to treat patients with rheumatoid arthritis, but their effect on joint destruction, as assessed radiologically, is uncertain.
METHODS: We conducted a randomized, double-blind trial comparing oral prednisolone (7.5 mg daily for two years) with placebo in 128 adults with active rheumatoid arthritis of less than two years' duration. Except for systemic corticosteroids, other treatments could be prescribed. The primary outcome variables were the progression of damage as seen on radiographs of the hand after one and two years, as measured by the Larsen index, and the appearance of erosions in hands that had no erosions at base line. The radiographs were viewed jointly by a radiologist and a rheumatologist who were unaware of the treatment assignment and the time point at which the films were obtained.
RESULTS: The statistical analysis of radiologically detected changes was based on 106 patients for whom there were films obtained at base line and two years later. After two years, the Larsen scores increased by a mean of 0.72 unit in the prednisolone group, indicating very little change, and by 5.37 units in the placebo group, indicating substantial joint destruction (P = 0.004). Of the 212 hands of these patients, 147 (69.3 percent) had no erosions at the start of the study. At two years, 15 of the 68 such hands in the prednisolone group (22.1 percent) and 36 of the 79 such hands in the placebo group (45.6 percent) had acquired erosions (difference, 23.5 percentage points; 95 percent confidence interval, 5.9 to 40.7; P = 0.007). The patients in the prednisolone group had greater reductions than the patients in the placebo group in scores on an articular index and for pain and disability at 3 months; for pain at 6 months; and for disability at 6, 12, and 15 months (all P < 0.05). There was no difference between groups in standardized scores for the acute-phase response. The adverse events were typical of those encountered with antirheumatoid drugs.
CONCLUSIONS: In patients with early, active rheumatoid arthritis, prednisolone (7.5 mg daily) given for two years in addition to other treatments substantially reduced the rate of radiologically detected progression of disease.
Long-term study of management of rheumatoid arthritis.
A 10-year study of the management of rheumatoid arthritis was conducted to compare a programme consisting of rest and anti-inflammatory and antirheumatic drugs with one consisting of maintenance of activity, anti-inflammatory and antirheumatic drugs, and systemic steroids where necessary. During this period subjects who did not respond to the treatment allocated went on to a combined treatment programme of rest, anti-inflammatory and antirheumatic drugs, and steroids. Among those who remained in the trial for the 10 years, there was little difference between the two groups in morning stiffness, number of inflamed joints, functional capacity, grip strength, number of American Rheumatism Association criteria present, and whether they remained on their original treatment programme or switched to the combined programme. However, in those who started in the steroid group, the condition of several joints tended to be better clinically and radiologically than in those of the other group during and at the end of 10 years of the original treatment programme, at time of transfer to the combined programme, and at the completion of the combined programme. Both groups had as many complications of disease and treatment, and adverse effects attributable to steroids seemed to be restricted to those with severe disease who had not responded to their original programme. A policy of maintaining physical activity plus the judicious use of steroids where required produces, in the long term, results as good as or probably better than a regimen of bed rest and no steroids.
Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial.
A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial.
Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial.
The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended.
Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment.
OBJECTIVE: Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.
METHODS: Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.
RESULTS: During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.
CONCLUSION: Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.
Options:
A: Corticosteroids were significantly more effective than placebo for most outcomes, and comparable to aspirin and chloroquine.
B: Corticosteroids were less effective than placebo for most outcomes, and inferior to aspirin and chloroquine.
C: Corticosteroids were equally effective as placebo for all outcomes, and superior to aspirin and chloroquine.
D: Corticosteroids were significantly more effective than placebo for all outcomes, but less effective than aspirin and chloroquine.
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A
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59
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the effectiveness of haloperidol decanoate compared to placebo, oral haloperidol, and other depot antipsychotics for the treatment of schizophrenia? Please answer this question based on the information provided below:
A randomized clinical trial of haloperidol decanoate and fluphenazine decanoate in the outpatient treatment of schizophrenia.
We carried out an 8-month double-blind clinical trial comparing haloperidol decanoate with fluphenazine decanoate in the maintenance treatment of 72 schizophrenic outpatients. A parallel-groups design was used with stratification by sex and injection interval (2, 3, or 4 weeks). The initial injection interval was based on pretrial maintenance treatment with fluphenazine esters. The dosage equivalency of haloperidol decanoate (1.5 cc or 75 mg) to fluphenazine decanoate (1 cc or 25 mg) used was 3:1. This remained approximately the same throughout a 2-month titration period with a flexible dose regimen, and a further 6-month period with a fixed dose regimen. No statistically significant differences in therapeutic effect were found between the drugs. Both drugs had a similar profile for drug-induced parkinsonism, but there was a trend for differences in masking tardive dyskinesia. Haloperidol and prolactin plasma concentrations were well correlated with dosage, with the exception of haloperidol concentrations in patients receiving injections at 2-week intervals.
A double-blind, controlled clinical trial of haloperidol decanoate and fluphenazine decanoate in the maintenance treatment of schizophrenia.
Weight gain and prolactin levels in patients on long-term antipsychotic medication: a double-blind comparative trial of haloperidol decanoate and fluphenazine decanoate.
A one year double-blind trial of haloperidol decanoate and fluphenazine decanoate was conducted in nineteen out-patients who had previously received at least one year's treatment with fluphenazine decanoate and were already overweight, as judged by a Body Mass Index of 25+. Although the difference was not statistically significant, patients treated with haloperidol decanoate showed a trend to less weight gain than patients who continued on fluphenazine decanoate, even though the haloperidol to fluphenazine dose ratio was 4:1. No statistically significant changes in mental state were observed and the incidence of extrapyramidal side-effects in the two treatment groups was similar.
Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.
Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.
Minimal effective dose and relapse--double-blind trial: haloperidol decanoate vs. placebo.
Fifty-six chronic schizophrenic patients were randomized into haloperidol decanoate (HD) or placebo groups for 48 weeks of double-blind treatment. The double-blind trial was preceded by a 15-week single-blind run-in period, during which all patients were treated with 60 mg of HD (approximately corresponding to 3.6 mg orally/day) every fourth week (except for the second injection, which was given after 3 weeks). Eight relapses occurred during the run-in period, and seven other patients refused further participation. The remaining 41 patients were then treated double blind, either with HD, 60 mg/4 weeks (18 patients), or with placebo (23 patients). Two patients (11%) in the HD group and 16 (69%) in the placebo group relapsed during the 48-week double-blind period. The plasma concentrations of haloperidol were measured every fourth week in both groups. Steady state was reached after 11 weeks. The mean steady-state level was 6.3 nmol/L. In the placebo group, a 50% decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol. The haloperidol plasma concentration was a predictor of relapse. There was no statistical difference between the treatment groups regarding extrapyramidal symptoms. More biperiden, however, was used in the HD group, while the placebo patients took more sedatives. The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)
Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention.
In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.
Haloperidol decanoate v. fluphenazine decanoate as maintenance therapy in chronic schizophrenic in-patients.
In a double-blind study of 38 chronic schizophrenic in-patients, haloperidol decanoate was compared with fluphenazine decanoate as maintenance therapy over 60 weeks. Both drugs were given by injection at 4-week intervals. Haloperidol and fluphenazine were assumed to be equipotent; the mean starting dose of the former was 127 mg and of the latter 106 mg. The number of withdrawals over 60 weeks was similar in both groups but relapses, strictly defined, were significantly more frequent in the haloperidol group. When patients were switched to haloperidol, Parkinsonism diminished more quickly than in the fluphenazine group, but after 60 weeks there was no difference in severity in the two drug groups. The higher relapse rate and the quicker reduction in Parkinsonism in the haloperidol group might be due to a misjudgement in equivalent doses of the two drugs. Plasma haloperidol steady state levels were reached in most patients by 8-12 weeks. Plasma neuroleptic and prolactin levels, week-by-week systemic drug availability and Parkinsonism showed less variation between injections with haloperidol than with fluphenazine.
A comparative trial of haloperidol decanoate and fluphenazine decanoate in chronic schizophrenic patients.
A twenty-week double-blind study was conducted to compare the efficacy and side-effect profile of haloperidol decanoate and fluphenazine decanoate, both given four-weekly, in fifty-one chronic schizophrenic patients. The mean dose of fluphenazine decanoate was 84 mg compared to 122 mg for the haloperidol decanoate group--suggesting a potency ratio of 1.0 : 1.4 in this study population. The CPRS sub-scale for schizophrenic symptoms showed a statistically significant improvement (p. less than 0.05) for the haloperidol decanoate group after twenty weeks treatment. A significant difference favouring haloperidol decanoate (p. less than 0.05) was also shown in the CPRS depression sub-scale at the end of the study. No significant between-group differences were found in the incidence of extrapyramidal side-effects at week 20, though consumption of the antiparkinsonian medication orphenadrine was significantly higher (p. less than 0.05) in the fluphenazine decanoate group (mean dose 102 mg) compared to a mean dose of 58 mg for the haloperidol decanoate group. More patients on fluphenazine decanoate gained weight than patients on haloperidol decanoate, but the difference was not statistically significant.
Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.
Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.
Options:
A: Haloperidol decanoate showed significant improvement in symptoms and behavior compared to placebo, but no differences were found when compared to oral haloperidol or other depot antipsychotics.
B: Haloperidol decanoate was less effective than placebo, oral haloperidol, and other depot antipsychotics in improving symptoms and behavior.
C: Haloperidol decanoate showed significant improvement in symptoms and behavior compared to oral haloperidol and other depot antipsychotics, but no differences were found when compared to placebo.
D: Haloperidol decanoate showed no significant differences in effectiveness compared to placebo, oral haloperidol, or other depot antipsychotics.
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A
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60
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the short-term effects of D-penicillamine on rheumatoid arthritis patients in terms of disease activity and adverse reactions? Please answer this question based on the information provided below:
Controlled trial of D(-)penicillamine in severe rheumatoid arthritis.
Synthetic D(-)penicillamine in rheumatoid arthritis. Double-blind controlled study of a high and low dosage regimen.
Doses of 600 mg and 1200 mg of D(-)penicillamine daily were superior to a standard regimen of therapy in rheumatoid arthritis. The higher dose did not produce significantly greater therapeutic benefit in the group of patients so treated, although individual patients sometimes improved more. The frequency of rashes, blood dyscrasias, and withdrawals from the trial increased withe dosage. It is concluded that D(-)penicillamine is a useful treatment that the daily dose should be as low as possible, and that it should be increased at infrequent intervals only, with due regard to the likelihood of further improvement in relation to an increased risk of adverse reactions.
Immunostimulant therapy with levamisole for rheumatoid arthritis.
In a controlled study involving thirty-four patients levamisole was shown to be as effective as D-penicillamine and more effective than placebo in the treatment of rheumatoid arthritis. Its action was slow and was accompanied by a reduction in erythrocyte sedimentation-rate, rheumatoid factor, and technetium index. These properties indicate that it has a specific action like that of D-penicillamine. Stimulation of cell-mediated immunity was evident in patients treated with levamisole, and there was a correlation between such changes and pain relief. Animal models confirmed the absence of anti-inflammatory effect and provided some evidence of enhancement of cell-mediated immunity and macrophage stimulation.
Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc.
The findings are reported of a controlled clinical trial comparing in 66 rheumatoid arthritis patients 0 g (placebo), and 0.50 g a day and 1 g a day of penicillamine. Each of these groups has been subdivided into two, one part receiving 5 mg a day of zinc metal supplement, the other a placebo. The trial was planned to be double-blind, and for each patient to take part for 4 months. The results prove the effectiveness of penicillamine in rheumatoid arthritis. 0.50 g a day has the same effect as 1 g a day but gives less side effects. Zinc supplement inhibits the clinical effects of penicillamine but does not prevent the side effects.
Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis.
In order to evaluate clinical efficacy of D-penicillamine (DP) a double-blind study was conducted by the Metalcaptase Research Group consisting of forty-one rheumatological centers in Japan. A total of 179 patients with rheumatoid arthritis (RA) was divided into two groups; one treated with 5 mg (control group) and the other with 100 mg (drug group) of DP in capsule form. The trial lasted 24 weeks. Global judgment by physicians revealed that improvement was found in 27% in the controls and 65% in the drug group. Adverse reactions occurred in 34% of the controls and 49% of the drug group. Skin rashes, taste disturbances, gastrointestinal upset and proteinuria were frequent in the drug group, but severe or fatal reactions could not be seen in this trial.
Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial.
Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity.
Options:
A: D-penicillamine showed no significant benefit over placebo in reducing disease activity and had no increase in adverse reactions.
B: D-penicillamine showed a significant benefit over placebo in reducing disease activity but had a higher incidence of adverse reactions.
C: D-penicillamine showed a significant benefit over placebo in reducing disease activity with no increase in adverse reactions.
D: D-penicillamine showed no significant benefit over placebo in reducing disease activity but had a higher incidence of adverse reactions.
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B
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61
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the short-term effects of azathioprine for the treatment of rheumatoid arthritis in terms of joint scores and adverse reactions? Please answer this question based on the information provided below:
Azathioprine in rheumatoid arthritis. A double-blind, cross over study.
Azathioprine in rheumatoid arthritis: double-blind study of full versus half doses versus placebo.
To test whether azathioprine in effective in rheumatoid arthritis in doses smaller than those normally used the drug was tested at 2 dosage levels, 2.5 and 1.25 mg/kg/day (2.5 AZ and 1.25 AZ), against placebo under double-blind conditions over 24 weeks. Dropouts were 7 out of 15 in the 2.5 AZ group, 4 out of 14 in the 1.25 AZ group, and 2 out of 13 in the placebo group. Some significant improvement occurred in all 3 groups, including those on placebo. However, the 2.5 AZ group fared significantly better than the placebo group, while the 1.25 AZ group results tended to fall between the other 2 groups. We conclude that, in order to obtain the reported effectiveness of azathioprine in rheumatoid arthritis, it is necessary to start treatment with 2.5 mg/kg/day. Halving this dosage reduces the effectiveness of the drug.
Options:
A: Azathioprine showed no significant benefit over placebo for tender joint scores and had fewer adverse reactions.
B: Azathioprine showed a statistically significant benefit for tender joint scores compared to placebo, but had significantly higher withdrawals due to adverse reactions.
C: Azathioprine showed a statistically significant benefit for tender joint scores compared to placebo, with no difference in adverse reactions.
D: Azathioprine showed no significant benefit over placebo for tender joint scores and had significantly higher withdrawals due to adverse reactions.
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B
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62
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the effect of peripheral retinal ablation on the incidence of adverse ophthalmic outcomes in premature infants with threshold retinopathy of prematurity (ROP)? Please answer this question based on the information provided below:
Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
Cryotherapy for Retinopathy of Prematurity Cooperative Group Reports from the 3- and 12-month follow-up examinations in the Multicenter Cryotherapy for Retinopathy of Prematurity trial indicated a beneficial effect of cryotherapy in the treatment of severe retinopathy of prematurity. This report provides results from the 3 1/2-year follow-up examination on 92% of the 256 survivors from the original cohort of 291 infants in the randomized trial. Functional outcome was evaluated by masked assessment of letter acuity using the HOTV crowded letter test and grating acuity using the Teller Acuity Card procedure. Structural outcome was evaluated by physician's assessment of retinopathy of prematurity residua in the posterior pole. All three outcome measures showed a reduction in unfavorable outcomes in treated vs control eyes: 46.6% vs 57.5% (P < .01) for letter acuity, 52.4% vs 65.6% (P < .001) for grating acuity, and 26.1% vs 45.4% (P < .001) for posterior pole status. These results support the long-term efficacy and safety of cryotherapy in the treatment of severe retinopathy of prematurity.
Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
This study of the safety and efficacy of cryotherapy in treating severe retinopathy of prematurity registered 9751 infants with birth weights less than 1251 g at 23 study centers. Two hundred ninety-one infants developed a defined threshold retinopathy of prematurity, and cryotherapy was performed in approximately half of the eyes through a randomization protocol. Twelve months after randomization, results of masked grading of fundus photographs of the posterior pole were similar to results obtained 3 months after randomization, and indicated an unfavorable outcome in 25.7% of the eyes that received cryotherapy compared with 47.4% of the control eyes (P less than .0001). For the first time, masked Teller Acuity Card assessment of grating acuity was performed in this study group and indicated an unfavorable functional outcome in 35.0% of the treated eyes compared with 56.3% of the control eyes (P less than .0001). These results indicate that cryotherapy reduces the risk of unfavorable retinal and functional outcome from threshold retinopathy of prematurity.
Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
We report the preliminary three-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied in one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degrees sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined three months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.
Multicenter trial of cryotherapy for retinopathy of prematurity. Snellen visual acuity and structural outcome at 5 1/2 years after randomization.
OBJECTIVE: To evaluate outcome at 5 1/2 years after randomization in eyes that underwent cryotherapy and in control eyes of patients in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity.
DESIGN: During infancy, patients with bilateral threshold retinopathy of prematurity (ROP) were assigned to receive cryotherapy for one eye and no cryotherapy for the other eye. Those with threshold ROP in only one eye (asymmetric) were randomly assigned to cryotherapy or no cryotherapy for that eye. Then, 5 1/2 years later, testers who were masked to the treatment status of each eye measured the patients' monocular visual acuity by using the log of the minimum angle of resolution visual acuity chart that was used in the Early Treatment of Diabetic Retinopathy Study. This was the most refined visual acuity testing yet performed on this cohort. Structural outcome was evaluated by participating ophthalmologists' assessment of ROP residua in the posterior pole of the fundus.
PATIENTS: Patients were 291 children who had been preterm infants with birth weights of less than 1251 g in whom threshold ROP had developed. Two hundred forty patients had bilateral threshold ROP, and 51 had threshold ROP in only one eye.
RESULTS: For the 234 children examined, both visual acuity and fundus structure showed a reduction in unfavorable outcomes in treated vs control eyes: 47.1% vs 61.7%, respectively (P<.005), for visual acuity and 26.9% vs 45.4%, respectively (P<.001), for fundus status. Detailed analysis of visual acuity outcomes for all eyes revealed that while fewer treated eyes (31.5%) than control eyes (48%) were blind (P<.001), there was a slight trend toward fewer eyes with a visual acuity of 20/40 or better in the treated (13%) vs control (17%) groups (P=.19).
CONCLUSIONS: The results support the long-term efficacy and safety of cryotherapy in the treatment of severe ROP. However, the data show preliminary evidence of a possible adverse effect of this treatment on visual acuity.
Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
We report the results of the national multicenter trial of cryotherapy for retinopathy of prematurity, as determined 3 months after randomization. The threshold severity of retinopathy required for entry into the clinical trial was defined as five or more contiguous or eight cumulative 30 degree sectors (clock hours) of stage 3+ retinopathy of prematurity in zone 1 or 2. Transscleral cryotherapy to the avascular retina was applied in one eye when there was threshold retinopathy in both eyes, or in half the eyes when the threshold severity existed in only one eye (18% of patients). Of the 279 infants who survived 3 months following randomization, 273 returned for outcome examination at that time. Of these infants, 260 had fundus photographs taken that could be graded for anatomic outcome. An unfavorable outcome was defined as posterior retinal detachment, posterior retinal fold (usually involving the macula), or retrolental tissue that obscured the view of the posterior pole. Whereas 51.4% of control eyes had an unfavorable outcome, this was significantly less frequent in the eyes that received cryotherapy (31.1%). No deaths were attributed to the cryotherapy procedure. These data, together with numerous additional ocular findings and preliminary 12-month postrandomization outcome results reported herein, support the efficacy of cryotherapy in reducing the risk of unfavorable ocular outcome from threshold retinopathy of prematurity. We have previously recommended cryotherapy for at least one eye in all patients with threshold retinopathy of prematurity. Now we add the recommendation cryotherapy be considered for both eyes whenever stage 3+ retinopathy of prematurity involves the posterior retina (zone 1) of both eyes.
Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
We report the preliminary 3-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied to one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degree sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined 3 months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.
Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study.
PURPOSE: To investigate the prevalence of color deficits at age 5 1/2 years in preterm children with birth weights of less than 1251 g who participated in the multicenter Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study.
METHODS: Two cohorts of CRYO-ROP participants served as subjects: 1055 children who participated in a long-term study of the natural history of ROP at 5 of the 23 CRYO-ROP centers, and 187 children (from all 23 study centers) who had threshold ROP in both eyes and who were randomized to receive cryotherapy in 1 eye. Monocular color vision was tested at age 5 1/2 years, using the Standard Pseudoisochromatic Plates, part 2 (SPP2) for acquired color vision defects.
RESULTS: In the Natural History cohort, prevalence of red-green (R-G) color deficits was 6.6% for males and 1.0% for females, similar to that of the general adult population. Prevalence of blue-yellow (B-Y) color deficits was 2.8% for males and 2.2% for females, more than 200 times that in the general adult population. Prevalence of B-Y deficits was not related to birth weight, gestational age, acute-phase ROP, optic atrophy, or retinal residua of ROP, but was related to visual acuity. In the Threshold ROP cohort, color vision deficits were no more likely in eyes that had received cryotherapy than in control eyes.
CONCLUSIONS: The results confirm an increased prevalence of B-Y deficits in children born before term, and provide evidence that the increased prevalence is not related to birth weight, gestational age, or severity of ROP within this group of preterm children. No evidence was found to indicate that cryotherapy increased the rate of color vision deficits in eyes with threshold ROP.
Partial retinal detachment at 3 months after threshold retinopathy of prematurity. Long-term structural and functional outcome. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity Cooperative Group.
OBJECTIVE: To investigate the structural and functional outcome at age 4 1/2 years of eyes that had partial retinal detachment (RD) at 3 months after the occurrence of threshold retinopathy of prematurity; these eyes were involved in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study.
METHODS: Of the 531 eyes in the randomized portion of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study, 61 had partial RD at the 3-month examination. The extent of retinal involvement was recorded, and the presence of a foveal detachment was noted. At the examination conducted at age 4 1/2 years, the fundus structure was graded into cicatricial retinopathy of prematurity outcome categories by study ophthalmologists, and the visual acuity was measured by masked examiners using the Teller Acuity Card procedure and the crowded HOTV recognition acuity test.
RESULTS: Of the 61 eyes, 7 eyes continued to have partial RD at age 4 1/2 years. Of the remaining eyes, 20 eyes had structural outcomes classified as favorable in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study, and 27 eyes had unfavorable structural outcomes. Data were unrecordable for 3 eyes and missing for 4 eyes. No difference in outcome was found for eyes with partial RD at 3 months that had undergone cryotherapy vs eyes that had served as controls. Only 6 eyes had a visual acuity better than 20/200. When partial RDs did not involve the fovea at 3 months, structural and functional outcomes at 4 1/2 years were better than when RDs involved the fovea. The best predictor of outcome was the extent of RD at 3 months.
CONCLUSIONS: Partial RD present 3 months after threshold retinopathy of prematurity is unstable anatomically, and the visual outcome is generally poor. Structure and function at 4 1/2 years are related to the extent of RD and the involvement of the fovea at 3 months.
Results of U.S. randomized clinical trial of cryotherapy for ROP (CRYO-ROP).
Twenty-three centers collaborated in this prospectively designed study involving infants born weighing less than 1251 grams. Patients examinations began 4 to 6 weeks from birth. For entry into the study, two investigators had to agree that an eye had developed stage 3 ROP involving a threshold number of at least 5 contiguous or 8 total clock hour sectors of zone 1 or 2, and 'plus' disease to a degree specified by a standard photograph. Cryotherapy was lightly applied to the avascular zone between the ridge of ROP and the ora serrata, in an average of about 50 separate spots. Outcome was determined 3 and 12 months following randomization, by means of masked readings of fundus photographs. Preliminary results were published in the Archives of Ophthalmology, Vol. 106, pp. 471-479, 1988. In these results from 172 of the 291 study patients, 43.0% of the control eyes had an adverse outcome (defined as retinal detachment, macular fold, or retrolental mass), as compared to 21.8% adverse outcome for eyes that received cryotherapy.
Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the cryotherapy for retinopathy of prematurity trial. The CRYO-Retinopathy of Prematurity Cooperative Group.
PURPOSE: To measure monocular visual field extent in very-low birth weight children in whom severe (threshold) acute-phase retinopathy of prematurity (ROP) developed in one or both eyes, and who had random assignment of eyes to cryotherapy or no cryotherapy. A control group of very-low birth weight children in whom ROP did not develop also was tested.
METHODS: There were 78 children in the severe ROP group from 5 of 23 centers in the randomized trial of cryotherapy for ROP (CRYO-ROP). The comparison cohort consisted of 75 study participants in whom ROP did not develop. All subjects had birth weights of less than 1251 g. At the 5 1/2-year study examination, visual field size was measured using double-arc kinetic perimetry. Testers were masked to treatment status of each eye. Four meridia were tested: superotemporal (ST), inferotemporal (IT), inferonasal (IN), and superonasal (SN). Target size was 6 degrees.
RESULTS: When blind eyes were assigned a score of 0 degree, the no-ROP, treated, and control eyes had an average visual field extent of 62 degrees, 35 degrees, 27 degrees at ST; 73 degrees, 42 degrees, 35 degrees at IT; 51 degrees, 30 degrees, 21 degrees IN; and 50 degrees, 26 degrees, 22 degrees at SN, respectively. Among 25 children who had bilateral threshold ROP and measurable fields in each eye, values for treated and control eyes were 59 versus 62 at ST, 69 versus 80 at IT, 44 versus 49 at IN, and 41 versus 48 at SN, respectively.
CONCLUSIONS: Overall, visual fields in eyes that reached threshold ROP were smaller than those of eyes that did not develop ROP. When only pairs of sighted eyes were considered, visual fields in the treated eyes were 6.4 degrees smaller than those of control eyes. Therefore, it appears that a small loss of peripheral field occurs when cryotherapy prevents the development of retinal detachment.
Measurement of Goldmann visual fields in older children who received cryotherapy as infants for threshold retinopathy of prematurity.
BACKGROUND: Cryotherapy administered to eyes with severe acute-phase (threshold) retinopathy of prematurity benefits retinal structure and visual acuity compared with the natural course of the retinopathy.
OBJECTIVES: To determine the extent of peripheral field abnormalities in eyes with threshold retinopathy of prematurity that had retinal structure preserved by cryotherapy.
METHODS: Kinetic perimetry was performed with a Goldmann perimeter by masked testers on patients in whom bilateral threshold retinopathy of prematurity developed and who had been randomly assigned to undergo cryotherapy in one eye and no cryotherapy in the fellow eye. With the V-4-e and the II-4-e targets, eight meridians were tested: 0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees. The median value of three presentations in each meridian was accepted as the extent in that meridian.
RESULTS: Fourteen eyes (eight treated and six control) of eight patients (mean age, 9.9 years; range, 6 to 11 years) had adequate vision to undergo fields testing. Mean (+/-SE) extent of visual field for treated vs control eyes was 36 degrees +/- 3 degrees vs 46 degrees +/- 6 degrees for the II-4-e target and 49 degrees +/- 4 degrees vs 59 degrees +/- 6 degrees for the V-4-e target. This difference was consistent across all eight meridians for either target, and repeated-measures analysis of variance showed that cryotherapy was associated with smaller visual field extent for both target sizes (P=.08).
CONCLUSION: The results of this small pilot study suggest that eyes that have retinal structure and acuity preserved by cryotherapy for severe acute-phase retinopathy of prematurity have slightly smaller visual fields than untreated eyes with severe acute-phase retinopathy of prematurity that had vision preserved.
A pilot study on cryotherapy and active retinopathy of prematurity.
Seventeen patients with symmetrical stage 3 retinopathy of prematurity (ROP) and plus disease were assign to cryotherapy in one eye. Treatment was confined to the avascular zone of retina. Twelve treated eyes (71%) improved and 10 untreated eyes (59%) became worse. However, in only five patients did the treated eye improve and the untreated eye become worse, a number too small to be statistically significant.
Management of retinopathy of prematurity.
Seventeen patients with symmetrical stage 3 retinopathy of prematurity (ROP) and plus disease as described in the International Classification of ROP had one eye randomized to cryotherapy and the other to control. Seventy-seven percent of the patients were under 1000 grams at birth and females outnumbered males by a 2 to 1 ratio. The average chronologic age at which cryotherapy was performed was three months. Twelve of seventeen treated eyes (71%) showed resolution of the ROP and 10 of 17 untreated eyes (59%) became significantly worse. However, only five patients had improvement in the treated eye and progression in the untreated eye, a number too small to provide statistical significance. Six eyes with Stage IV ROP were operated by encircling scleral buckling techniques because of total retinal detachment secondary to peripheral traction and cicatrization arising from the ridge. In five patients the unoperated eye had already developed a retrolental membrane, and in one patient bilateral detachments were present. Five of the six operated retinas were reattached.
Cryotherapy for active retinopathy of prematurity.
Twenty-eight patients with bilateral symmetrical stage-III retinopathy of prematurity and plus disease had one eye treated using cryotherapy, while the other acted as a control. Eleven patients showed improvement in both the treated and untreated eye, while 11 others were noted to improve in the treated eye while demonstrating deterioration in the untreated eye. The P value obtained by applying binomial distribution tests suggested that, in the sampled population, cryotherapy was preferable to no treatment.
Cryotherapy for active retinopathy of prematurity.
Twenty-eight patients with bilateral symmetrical stage-III retinopathy of prematurity and plus disease had one eye treated using cryotherapy, while the other acted as a control. Eleven patients showed improvement in both the treated and untreated eye, while 11 others were noted to improve in the treated eye while demonstrating deterioration in the untreated eye. The P value obtained by applying binomial distribution tests suggested that, in the sampled population, cryotherapy was preferable to no treatment.
Cryotherapy for active retinopathy of prematurity.
Twenty-eight patients with bilateral symmetrical Stage 3 retinopathy of prematurity (ROP) and plus disease had one eye assigned to cryotherapy and the other to control. The majority of patients weighed under 1000 grams at birth and females outnumbered males by nearly a two-to-one ratio.+ Cryotherapy was generally performed at a gestational age of less than 40 weeks and a mean chronologic age of 10 weeks. Eleven patients showed improvement in both the treated and untreated eyes possibly due to variables among prematures not identified in the study. Eleven other patients experienced improvement in the treated eye and progression in the untreated eye. Using the binomial distribution on the latter group the P value was 0.0005 with a one-tailed hypothesis test and 0.001 with a two-tailed test, suggesting that in the sampled population cryotherapy appears to be preferred over no treatment.
Options:
A: Peripheral retinal ablation increases the risk of early unfavorable retinal structure and unfavorable visual acuity in early childhood.
B: Peripheral retinal ablation has no significant effect on the incidence of adverse ophthalmic outcomes in premature infants with threshold ROP.
C: Peripheral retinal ablation reduces the incidence of early unfavorable retinal structure, unfavorable retinal structure in early childhood, and unfavorable visual acuity in early childhood.
D: Peripheral retinal ablation only reduces the incidence of early unfavorable retinal structure but has no effect on visual acuity.
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C
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the main findings regarding the use of prophylactic vancomycin in preterm neonates for the prevention of late-onset sepsis? Please answer this question based on the information provided below:
Selective use of vancomycin to prevent coagulase-negative staphylococcal nosocomial bacteremia in high risk very low birth weight infants.
OBJECTIVE: To determine whether vancomycin added to parental nutrition (PN) fluids could prevent nosocomial infections in very low birth weight newborns and which infants would benefit most from prophylaxis.
DESIGN: Double blind, randomized controlled study.
SETTING AND STUDY POPULATION: Very low birth weight infants receiving PN in a tertiary neonatal intensive care unit.
METHODS: Thirty-eight infants with and without central vascular catheters were randomized to receive no medication or 25 microg/ml vancomycin added to PN for the duration of the infant's PN requirements.
RESULTS: The addition of 25 microg/ml vancomycin to PN prevented bacteremia in very low birth weight infants receiving PN. There was a significant reduction in the number of coagulase-negative staphylococcal (CONS) bacteremias (defined as isolation of the same organism from two positive blood cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving vancomycin. Infants with birth weights of < 1000 g who received corticosteroids for treatment of chronic lung disease benefitted most from treatment. No vancomycin-resistant strains of CONS or enterococci were detected during the study period.
CONCLUSIONS: Prophylactic treatment with vancomycin effectively prevented CONS bacteremia under the conditions of the study. Its use was most effective in infants with birth weights of <1000 g.
Low-dose vancomycin prophylaxis reduces coagulase-negative staphylococcal bacteraemia in very low birthweight infants.
Very low birthweight (VLBW) infants undergoing neonatal intensive care are at risk of infection with coagulase-negative staphylococci (CONS). This study investigates the efficacy of twice daily, 1 h infusions of vancomycin (5 mg kg) in reducing CONS infection in VLBW infants receiving parenteral nutrition. Of 72 infants in the study, 37 were randomized to vancomycin and 35 to the control group. Clinical variables and mortality were similar in both groups. In the vancomycin group, 11 infants had one or more episodes of CONS bacteraemia compared with 17 in the control group. Two babies in the treatment group had more than one episode of CONS bacteraemia, compared with nine in the control group (P = 0.02). There were 13 episodes of CONS bacteraemia in the vancomycin group compared with 29 in the control group. When only positive blood-cultures associated with a rise in C-reactive protein were considered, there were six episodes of CONS bacteraemia in the vancomycin group compared with 18 in the control group. Similarly there were five infants with one or more CONS infections compared with 11 in controls and one with more than one episode compared with six in the control group (P = 0.05). Prophylaxis with intermittent low-dose vancomycin infusions may help reduce recurrent CONS bacteraemia in VLBW infants receiving parenteral nutrition.
Prevention of gram-positive sepsis in neonates weighing less than 1500 grams.
A prospective, randomized study to evaluate the effectiveness of a continuous low-dose vancomycin infusion to prevent nosocomial gram-positive bacteremia was initiated within the first 2 weeks of life in neonates weighing < 1500 gm. Seventy-one infants received constant infusion of vancomycin (25 micrograms/ml) mixed with their total parenteral nutrition solution; 70 infants served as control subjects. The groups were clinically similar in birth weight, estimated gestational age, and severity of illness. Administration of vancomycin was begun at a mean age of 5.4 +/- 2.9 days. Infants had mean serum vancomycin concentrations of 2.4 micrograms/ml, and received vancomycin for a mean of 11 +/- 7 days. No vancomycin-resistant organisms were detected in surveillance cultures during the 2-year study period. Twenty-four of seventy control infants, in comparison with 1 of 71 infants receiving vancomycin, had gram-positive bacteremia (p < 0.001). The addition of a low dose of vancomycin to alimentation fluids virtually eliminated the incidence of gram-positive bacteremia in an at-risk population of very low birth weight infants. However, the widespread use of vancomycin in total parenteral nutrition solution is not recommended until better data on the emergence of vancomycin-resistant organisms are available.
[Preventive antibiotic administration for prevention of nosocomial septicemia in very small premature infants (VLBW infants)--preventive vancomycin administration against infections with coagulase negative streptococci--prevention of translocation with oral cefixime therapy in intestinal colonization with pathogenic gram-negative pathogens].
VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase-negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically.
Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates.
A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition--either the standard solution or a solution containing 25 micrograms of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days (p = 0.014)). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms.
Options:
A: Prophylactic vancomycin significantly reduced the incidence of total neonatal nosocomial sepsis and coagulase negative staphylococcal sepsis, but had no significant effect on mortality, length of stay, or vancomycin toxicity.
B: Prophylactic vancomycin significantly reduced the incidence of total neonatal nosocomial sepsis and coagulase negative staphylococcal sepsis, and also significantly reduced mortality and length of stay.
C: Prophylactic vancomycin had no significant effect on the incidence of total neonatal nosocomial sepsis, coagulase negative staphylococcal sepsis, mortality, length of stay, or vancomycin toxicity.
D: Prophylactic vancomycin significantly increased the incidence of vancomycin resistant organisms, leading to higher mortality and longer length of stay.
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A
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the efficacy of calcitonin in preserving bone mass and preventing fractures in patients with corticosteroid-induced osteoporosis? Please answer this question based on the information provided below:
Salmon calcitonin nasal spray in the prevention of corticosteroid-induced osteoporosis.
The objectives were to determine the efficacy and safety of nasal salmon calcitonin 200 IU daily in the prevention of corticosteroid-induced osteoporosis. A minimized, double-blind, placebo-controlled trial was carried out in corticosteroid-treated patients with polymyalgia rheumatica. The setting was a tertiary care university-affiliated hospital and a total of 31 patients were enrolled. The primary outcome measure was the percentage change in bone mineral density of the lumbar spine in the two treatment groups from baseline to 1 yr of follow-up. The mean +/- S.D. bone mineral density of the lumbar spine in the calcitonin-treated group decreased by 1.29 +/- 6.76% and in the placebo group by 4.95 +/- 3.50% after 12 months. The observed difference of 3.65 +/- 2.10% between groups is statistically significant (P < 0.05). Nasal salmon calcitonin prevented loss of bone in the lumbar spine as measured by dual-energy X-ray absorptiometry.
[Intranasal salmon calcitonin for the prophylaxis of bone mineral loss in steroid-treated chronic obstructive lung diseases ].
In the present controlled study the effect of calcitonin nasal spray (CAS 47931-85-1; Lachs-Calcitonin Nasal spray Sandoz) on the bone mineral content was investigated in 36 patients in need of corticosteroid therapy suffering from chronic, obstructive lung diseases. The treatment consisted of 200 IU intranasal daily and lasted for one year. In the control group there was a statistically significant decline of bone mineral content of 5% or 4.3% concerning the lumbar vertebrae L1-L4 and the femur, whereas in the treated group there was only a statistically not significant decrease of 0.9% and 0.8%, respectively. These findings show that calcitonin nasal spray in a dose of 200 IU daily is quite useful for the prophylaxis of steroid-induced osteoporosis.
A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica.
Patients treated with high-dose or long-term corticosteroids are at risk of accelerated osteoporosis and spontaneous vertebral and traumatic fractures. To assess the efficacy of salmon calcitonin in preventing corticosteroid- induced osteoporosis, 48 patients with newly diagnosed polymyalgia rheumatica, temporal arteritis, and other vasculitides were enrolled in a 2-year, double-blind, randomized, controlled trial. Patients were randomized to receive subcutaneous injections t.i.w. of either 100 IU of salmon calcitonin (25 patients) or placebo (23 patients). After 2 years, 19 and 21 patients, respectively, were evaluable. All patients also received supplemental calcium carbonate (1500 mg daily in divided doses) and vitamin D3 (400 IU daily). Baseline and serial radiologic assessments included dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip, and spine radiographs to detect vertebral fractures. There were no significant baseline differences between the two study groups. The mean within-subject percentage change in DXA lumbar spine density in the two groups over the 2-year period of the study was only -0.1% (calcitonin plus calcium) versus -0.2% (placebo plus calcium) a nonsignificant difference despite the high mean cumulative corticosteroid doses of 5371 mg and 4680 mg, respectively (NS). The incidence of vertebral fracture was 12.5% (calcitonin plus calcium: 11%, versus placebo plus calcium: 14%, NS), with four fractures in the first year and one fracture in the second year. Higher cumulative cortico-steroid dose was associated with a greater loss in bone density. In rheumatic disease patients starting high-dose, long-term corticosteroids, salmon calcitonin with calcium and vitamin D3 provided no greater bone preservation than that observed with calcium and vitamin D3 alone.
Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoid therapy?
OBJECTIVE: To investigate the efficacy of intranasal salmon calcitonin (sCT) in treating axial bone loss in patients with rheumatoid arthritis (RA) taking low dose glucocorticoids.
METHODS: In this open, multicenter study 32 women with RA were treated one year with sCT 100 IU/day and calcium (Ca) 500 mg/day; 31 women were treated with Ca alone. Bone mineral density (BMD) was measured at the lumbar spine and proximal femur (femoral neck, Ward's triangle, trochanter) before sCT therapy and again after 6 and 12 months.
RESULTS: Among valid completers treated with sCT and Ca (n = 26), the mean BMD increased at the lumbar spine (L1-L4), femoral neck, and Ward's triangle. In contrast, valid completers treated with Ca (n = 23) showed bone loss at the spine (L1-L4), femoral neck, Ward's triangle, and trochanter area. The differences of the changes in BMD were statistically significant between these groups at the femoral neck, Ward's triangle, and trochanter. There were no significant differences between groups in bone loss over 12 months at the lumbar spine (L1-L4), although analysis of the upper segment (L1-L2) suggested some possible benefit of sCT.
CONCLUSION: Intranasal sCT (100 IU/day) appears to have beneficial effects on bone loss at the proximal femur in patients with active RA treated with low dose glucocorticoids for 12 months; longer studies are needed to exclude transient bone remodelling effects.
Treatment of steroid-induced osteopenia with calcitonin in corticosteroid-dependent asthma. A one-year follow-up study.
Sixty-two steroid-dependent asthmatics who had not received any form of treatment to prevent bone loss were studied during a 12-month period. Patients were randomly divided into two groups. Thirty-one patients were treated with 1 g of elemental calcium taken daily plus 100 IU of salmon calcitonin every other day, administered subcutaneously; the remaining 31 patients received only calcium supplementation. In the calcitonin group, 11 patients dropped out of the study because of severe side effects (seven patients), lack of compliance (three patients), and exacerbation of asthma (one patient). The 20 patients who completed the 12-month follow-up period were analyzed and compared with 20 sex-matched patients from the control group. At one year, bone mineral density (BMD) had increased in the calcitonin group by a mean of 4% (p less than or equal to 0.001), whereas in the control group BMD had decreased by 2.5% (p less than or equal to 0.05). Parameters of bone remodeling (alkaline phosphatase and osteocalcin) decreased significantly in the calcitonin-treated group but not in the control group. Our findings show that calcitonin 100 IU, given three times/wk, is an effective drug in the treatment of steroid-induced osteopenia. Side effects, however, are frequent and cause a high degree of dropout from therapy. These findings suggest that further studies should be carried out with lower doses of calcitonin or by other better tolerated forms of delivery such as in a nasal spray.
Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study.
BACKGROUND: Injectable calcitonin is effective in reducing spinal bone loss in steroid-dependent asthma but side effects are frequent. In contrast, a nasal spray presentation has been shown to be effective and well tolerated in involutional osteoporosis. To test the efficacy of nasal calcitonin a two year prospective trial was conducted in 44 steroid-dependent asthmatic patients.
METHODS: All patients received a calcium supplement of 1000 mg and were allocated randomly into two groups treated with either salmon calcitonin nasal spray (200 IU every other day, n = 22) or calcium alone (n = 22) for two years. All patients completed the first year of the study. Five patients in each group dropped out during the second year. In the calcitonin group one patient developed generalised pruritus and four lost steroid dependence, and in the calcium alone group five were no longer dependent on steroids. The efficacy of treatment was evaluated as follows: bone turnover assessed by biochemical markers, bone loss assessed by serial measurement of lumbar spine density, and rates of bone fractures.
RESULTS: The bone mass in the calcitonin group increased by 2.7% in the first year while in the group receiving calcium alone it decreased by 2.8%; this difference was significant. Calcitonin prevented more bone loss during the second year while the calcium alone group continued losing bone mass (-7.8%). The difference between means was 0.1077 (95% CI 0.0381 to 0.1773). Three new fractures occurred in both groups. No changes in biochemical parameters were detected in either group.
CONCLUSIONS: Calcitonin given intranasally increased spinal bone mass during the first year of treatment and maintained bone mass in a steady state during the second year. These results suggest that calcitonin may be a useful agent to prevent steroid-induced osteoporosis. However, the lack of effect of calcitonin on the rate of vertebral fractures does not permit its recommendation for routine use in preventing steroid-induced osteoporosis.
Salmon calcitonin in the therapy of corticoid-induced osteoporosis.
There is uncertainty about the best treatment for steroid-induced osteoporosis. Thirty-six patients with steroid-dependent, chronic obstructive lung disease and associated steroid osteoporosis have been studied, of whom 18 were treated with salmon calcitonin and the other 18 served as controls. Treatment lasted for 6 months and consisted of 100 I.U.s.c. every other day. In the controls there were significant decrements of 1.4% and 3.5%, respectively, in cortical and cortical and trabecular bone mineral content, whereas in subjects on calcitonin there were increments of 2.6% and 2.7%, respectively. Additional evidence of positive effect of calcitonin was derived from the reduced incidence of new fractures occurring during the observation period. A significant reduction in back pain was a further consequence of the hormone therapy.
Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin.
BACKGROUND: Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin.
METHODS: One hundred three patients starting long-term corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year.
RESULTS: Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, -0.2 and -1.3 percent per year, respectively) than calcium alone (-4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (-2.3 percent per year). The calcitriol group also lost lumbar bone (-3.6 percent per year) but received more corticosteroid in the second year than the other two groups.
CONCLUSIONS: Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.
Options:
A: Calcitonin significantly preserves bone mass at the lumbar spine and femoral neck, and reduces the risk of vertebral and nonvertebral fractures.
B: Calcitonin preserves bone mass at the lumbar spine but not at the femoral neck, and does not significantly reduce the risk of vertebral and nonvertebral fractures.
C: Calcitonin does not preserve bone mass at the lumbar spine or femoral neck, but significantly reduces the risk of vertebral and nonvertebral fractures.
D: Calcitonin preserves bone mass at both the lumbar spine and femoral neck, but does not significantly reduce the risk of vertebral and nonvertebral fractures.
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B
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65
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effectiveness of multidisciplinary rehabilitation for fibromyalgia and widespread musculoskeletal pain among working age adults? Please answer this question based on the information provided below:
A randomized, controlled clinical trial of education and physical training for women with fibromyalgia.
OBJECTIVE: To determine the effectiveness of self-management education and physical training in decreasing fibromyalgia (FMS) symptoms and increasing physical and psychological well being.
METHODS: A pretest-posttest control group design was used. Ninety-nine women with FMS were randomly assigned to 1 of 3 groups; 86 completed the study. The education only group received a 6-week self-management course. The education plus physical training group received the course and 6 h of training designed to assist them to exercise independently. The control group got treatment after 3 months.
RESULTS: The experimental programs had a significant positive impact on quality of life and self-efficacy. Helplessness, number of days feeling bad, physical dysfunction, and pain in the tender points decreased significantly in one or both of the treated groups when retested 6 weeks after the end of the program. Longterm followup of 67 treated subjects showed significant positive changes on the Fibromyalgia Impact Questionnaire primarily in the physical training group. Among all subjects, 87% were exercising at least 3 times/week for 20 min or more; 46% said they had increased their exercise level since participating in the program; 70% were practicing relaxation strategies as needed; 46% were working at least half time as opposed to 37% at pretest.
CONCLUSION: Self-efficacy of the treated groups was enhanced significantly by the program. Other changes were smaller and more delayed than had been expected. Recommendations for future trials include a longer education program, more vigorous physical training, and longterm followup.
Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. II. Economic evaluation.
OBJECTIVE: In this 3 year randomized clinical trial the cost effectiveness of a 6 week educational/cognitive intervention (ECO) is compared with an educational discussion intervention (EDI) and a waiting list condition (WLC).
METHODS: A total of 131 patients with fibromyalgia were randomly allocated to the ECO, EDI, or WLC intervention. The ECO and EDI groups were followed for 12 months, whereas the WLC group was followed for 6 weeks. Direct health care and nonhealth care costs, and the indirect costs associated with lost production due to illness, were calculated. The effects were measured in terms of utilities, using rating scale and standard gamble methods.
RESULTS: Treatment costs were estimated to be US $980 per patient for both ECO and EDI. The total direct health care costs of ECO treatment were US $1623 higher than those for EDI. This difference was significant. Indirect costs for the 2 groups were not significantly different. At 6 weeks there was a significant difference in rating scale utilities between the 3 groups, caused by a significantly greater improvement in the EDI group compared to the WLC group. However, no significant differences in either rating scale or standard gamble utilities were found between the ECO and EDI groups immediately after treatment, or at the 6 or 12 month followups.
CONCLUSION: The economic evaluation showed that the addition of a cognitive component to the educational intervention led to significantly higher health care costs and no additional improvement in quality of life compared to the educational intervention alone. This conclusion is robust through a range of plausible values used in a sensitivity analysis.
Evaluation of a Swedish version of the arthritis self-efficacy scale in people with fibromyalgia.
The major purpose of this study was to determine the utility and construct validity of the Swedish version of the Arthritis Self-Efficacy Scale (ASES-S). Ninetynine women with fibromyalgia (FS) were included in a randomized, controlled trial of fibromyalgia efficacy-based self-management education and physical training. Several self-report instruments were used to evaluate the outcome of the intervention. Evidence of construct validity of the ASES-S was revealed in the factor analysis which produced a three factor solution similar to previous results. Significant correlations between ASES-S and pre and post health status measures were consistent with theoretically derived hypotheses, further testifying to construct validity. Multiple regression analyses confirmed that pretest ASES-S was the strongest predictor of posttest ASES-S. The results indicated that the intervention had produced a significant change in ASES-S and that this positive change in self-efficacy was associated with changes in health status. In conclusion, this study has shown the ASES-S to be a valid measure of treatment effects also for patients with FS.
A comparison of behavioral and educational interventions for fibromyalgia.
OBJECTIVE: To compare a comprehensive behavioral intervention with an education/control condition in the treatment of patients with fibromyalgia (FM), and to explore the role of mediators of clinical improvement in both groups.
METHODS: The effects of the behavioral and education/control interventions were evaluated across a 10 week treatment period and at 6 month followup on measures of pain, depression, disability, pain behaviors, and intervening variables. The behavioral intervention focused on the development of diverse pain coping skills, while the education/control condition presented information on a range of health related topic without emphasizing skill acquisition.
RESULTS: Although improvement across time was found in depression, self-reported pain behaviors, observed pain behaviors, and myalgia scores, no differences in these criteria were found between the behavioral and education/control conditions. Multiple regression analyses revealed that changes in helplessness and passive coping were associated with improvement in a number of clinical outcomes.
CONCLUSION: The findings illustrate the value of psychoeducational interventions in decreasing the psychological and behavioral effect of FM, and the value of reducing dysfunctional coping and helplessness in future intervention research.
Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I. Clinical effects.
OBJECTIVE: This randomized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia (FM) syndrome. We hypothesized that the combination of group education with cognitive treatment aimed at developing pain coping skills would be more effective than group education alone.
METHODS: 131 patients with FM were randomly assigned to 3 conditions: an experimental condition, which was the combined cognitive/educational intervention (ECO); an attention control condition consisting of group education plus group discussion (EDI); and a waiting list control (WLC). For the treatment conditions ECO and EDI, assessments were made 2 weeks before treatment, at start of treatment, at post-treatment, and at 6 and 12 mo followup. WLC patients received only 3 assessments.
RESULTS: There were no pretreatment differences between the groups, or between dropouts and patients who remained in the study. At post-treatment, and compared with the WLC, the ECO patients improved in knowledge about FM (p = 0.007) and pain coping (p < 0.001). EDI patients improved on pain coping (p = 0.005) and pain control (p = 0.002). EDI patients reported significantly less fear than ECO patients (p = 0.005). There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup. Based on the reliability of change index for clinical significance, the relative short term success rates are 6.4 and 18.4% for ECO and EDI, respectively.
CONCLUSION: The surplus value of a highly structured, 12 session group cognitive treatment added to group education cannot be supported by our study. In EDI, fear reduction might have enhanced pain coping and pain control, while poor compliance, the difficulty of homework assignments, and lack of individual support may have limited the effectiveness of ECO.
Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.
To determine and compare short- and long-term effects of aerobic exercise (AE), stress management treatment (SMT), and treatment-as-usual (TAU) in fibromyalgia, 60 patients were randomized to 14 weeks of treatment by either AE, SMT or TAU. Outcome measures at baseline, midway through treatment, at treatment completion, and at 4 year follow up included a patient made drawing of pain distribution, dolorimetry of tender points, ergometer cycle test, global subjective improvement, and VAS registrations of: pain, disturbed sleep, lack of energy, and depression. Both AE and SMT showed positive short-term effects. AE was the overall most effective treatment, despite being subject to the most sceptical patient attitude prior to the study. At follow up, there were no obvious group differences in symptom severity, which for AE seemed to be due to a considerable compliance problem.
A randomized prospective study of vocational outcome in rehabilitation of patients with non-specific musculoskeletal pain: a multidisciplinary approach to patients identified after 90 days of sick-leave.
This study was designed to evaluate the effectiveness of a multidisciplinary rehabilitation programme offered to a general population with 90 days of sick-leave due to non-specific musculoskeletal pain. The results concerning return to work and re-sick-listing during a follow-up period of five years were evaluated for Swedes and immigrants separately. Compared to a control group, the rehabilitation offer resulted in improved work stability after work return among the Swedes. The immigrants, as a group, did not benefit from the programme compared to the controls in primary care.
A controlled study of the effects of applied relaxation and applied relaxation plus operant procedures in the regulation of chronic pain.
Chronic back/joint pain patients participated in a comparative study of relaxation and operant therapies for chronic pain. Patients were randomly assigned to: (1) a waiting-list control, or to either (2) an applied relaxation, or (3) an applied relaxation plus operant conditioning treatment programme. Waiting patients were subsequently randomly assigned to active treatment. The results indicated that the treatment groups tended to do significantly better than the waiting-list control group for pain, medicine use, activity, and depression, but there were few clear differences between the treatment groups. Applied relaxation plus the operant programme was significantly better than relaxation for medicine reduction, and applied relaxation was better than relaxation and operant conditioning for a patient evaluation of reaching treatment goals. Within-group and single-subject analyses indicated that there were significant improvements between pre- and post-tests for the treatment groups, but not for the waiting-list control group. Follow-up data indicated maintenance, and that applied relaxation had significantly lower pain ratings than applied relaxation plus operant conditioning. Taken as a whole, the results show that applied relaxation can produce significant decreases in pain, and that the addition of an operant programme does not improve pain reductions, but does tend to improve results with activity and especially medicine intake variables.
Outpatient group treatment of chronic pain: effects of spouse involvement.
Options:
A: There is strong scientific evidence supporting the effectiveness of multidisciplinary rehabilitation for these conditions.
B: There is little scientific evidence supporting the effectiveness of multidisciplinary rehabilitation for these conditions.
C: Multidisciplinary rehabilitation has been proven to be highly effective in the short term but not in the long term.
D: Multidisciplinary rehabilitation is effective only when combined with medication.
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B
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66
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the efficacy and toxicity of auranofin in the treatment of rheumatoid arthritis compared to placebo? Please answer this question based on the information provided below:
Auranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a multicenter trial.
In a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life.
The cost effectiveness of auranofin: results of a randomized clinical trial.
In a 6-month randomized trial at 14 sites, the cost effectiveness of auranofin (AF) treatment for patients with rheumatoid arthritis was gauged in comparison with placebo. Measures of global health and of impacts on daily life suggest that the benefits of disease modification outweigh adverse effects after 4 and 6 months of treatment (p less than 0.01), with negligible differences between placebo and treated patients after 1 and 2 months. Additional medical costs directly associated with AF treatment amounted to $778/patient annually. Observed differences in less direct medical costs, help received, and earnings were not statistically significant.
Placebo-controlled comparison of oral gold with injectable gold in early rheumatoid arthritis.
Auranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis.
The efficacy, toxicity and possible steroid-sparing properties of auranofin in the treatment of elderly-onset rheumatoid arthritis (EORA) were studied in a 2 yr prospective double-blind placebo-controlled clinical trial. Sixty-five patients with onset of arthritis after the age of 60 yr were randomized to either auranofin 3 mg b.i.d. [n = 31, age 70 (61-84) yr, median (range)] or placebo tablets [n = 34, age 72 (60-81) yr]. Oral prednisolone, starting dose 7.5 or 20 mg daily, was used as a rescue drug in patients with intolerable joint pain and stiffness and with C-reactive protein (CRP) > or = 20 mg/l, and was tapered down according to protocol guidelines. Patients receiving auranofin continued therapy for a longer period of time (55% completers) than those on placebo medication (18% completers). The auranofin group consumed significantly less prednisolone, 2.64 (0-11.85) mg/day [median (range)], compared to 5.0 (0-18.33) mg/day in the placebo group (P = 0.006). No group differences at 2 yr follow-up were found for changes in joint pain (P = 0.49), number of swollen joints (P = 0.61), Health Assessment Questionnaire score (P = 0.18) and radiographic damage score (Larsen-Dale index) of the hands (P = 0.84). Within-group changes in radiographic scores were also insignificant. The drop-out rate due to adverse events was surprisingly higher in the placebo group (41%) than in the auranofin group (10%) and, as expected, higher due to lack of effect (29 and 16%). The results indicate that auranofin is safe, superior to placebo and has steroid-sparing capacity in the treatment of EORA. The favourable radiographic outcome in both groups needs confirmation in future studies.
Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study.
The effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se
Auranofin (SK&F) in early rheumatoid arthritis: results from a 24-month double-blind, placebo-controlled study. Effect on clinical and biochemical assessments.
In a 2-year, randomized, double-blind Nordic multicentre trial, auranofin was compared with placebo in early (disease duration less than or equal to 2 years), active rheumatoid arthritis (RA). Efficacy and safety were analysed in 67 patients receiving auranofin and 65 receiving placebo. Life table analysis demonstrated a significantly higher withdrawal rate due to insufficient therapeutic effect in the placebo group, whereas more patients dropped out due to side effects in the auranofin group. More auranofin than placebo patients (35 vs. 24) completed the 2 years. Clinical and inflammatory activity improved in both groups, but consistently more so in the auranofin group, in spite of the greater consumption of local steroids and NSAIDs in the placebo group. The most frequent side effects leading to withdrawal in the auranofin group were cutaneous and gastrointestinal reactions. The study demonstrated that most patients exhibit improvement in clinical signs and symptoms and about half of all patients with early RA continue to take auranofin for at least 2 years.
Oral gold: a comparison with placebo and with intramuscular sodium aurothiomalate.
The therapeutic and toxic effects of the orally absorbed gold compound auranofin have been compared with placebo and parenterally administered sodium aurothiomalate (GST) in 90 patients with active rheumatoid arthritis over one year. At the end of this period 57% of patients on auranofin, 73% on GST and 0% on placebo remained on therapy. Toxicity caused discontinuation of therapy in 10% of patients on auranofin, 20% on GST and 7% on placebo. Lack of response to therapy led to withdrawal of 20% on auranofin, 0% on GST and 90% on placebo. Multiple clinical and biochemical assessments were performed during this study. Analysing them separately, and in the case of 6 of them grouped together in a disease activity index, the same trend is apparent throughout, namely that placebo has no effect on active inflammatory rheumatoid arthritis, and that both gold drugs are beneficial. GST has an earlier effect and tends to produce a greater change but after one year there was no significant difference between the 2 gold drugs for any parameter assessed. Gold levels in plasma or erythrocytes did not predict or correlate with either the development of toxicity or clinical efficacy. This study has demonstrated the second-line potential of auranofin which seems to be effective at gold concentrations in the blood below those observed with GST therapy. Toxicity limits the use of gold salts in RA. If the reduced incidence of adverse reaction with auranofin observed in this study is substantiated in larger numbers over prolonged periods, the use of gold at an earlier stage of disease may be facilitated.
Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. Subsets of responses.
A comparison of placebo, auranofin, and parenteral gold sodium thiomalate therapy in 209 patients with active rheumatoid arthritis was performed in a 21-week prospective, controlled, double-blind multicenter trial. When the 161 patients who completed at least 20 weeks of treatment were analyzed for different degrees of response, no remissions were identified. When 50 percent or greater improvement of pain/tenderness scores were compared for end of trial versus entry values, 9 percent of placebo-treated patients, 34 percent of auranofin-treated patients, and 48 percent of gold sodium thiomalate-treated patients showed important improvement that was statistically significant for both gold treatments. When 50 percent improvement for joint swelling was analyzed, 12 percent of the placebo-treated group, 28 percent in the auranofin-treated group, and 37 percent in the gold sodium thiomalate-treated group showed this degree of improvement. Auranofin almost achieved statistical significance for improvement in joint swelling when compared with placebo (p = 0.07), but gold sodium thiomalate was much better than placebo (p = 0.009). There was no statistically significant difference between the two gold treatments. Thus it appears that a subset of patients had an important response to gold therapy that would not be evident by the usual analyses of mean or median changes. Analysis for predictors of response did not discriminate between responders and nonresponders. Because the trial was limited to 21 weeks of therapy, no prediction of the longer-term-effects, especially for auranofin, should be inferred.
Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.
A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, "nitritoid" reactions, and "gold pneumonitis" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.
Comparison of oral and parenteral gold therapy and placebo in the treatment of rheumatoid arthritis.
Two hundred and eight patients entered a prospective, controlled, double-blind multicenter trial comparing auranofin, gold sodium thiomalate (GST), and placebo. One hundred and sixty-one patients completed at least 20 weeks of therapy. No remissions were seen in the trial. Response to a variety of measures of efficacy was generally modest for both gold treatment groups. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated statistical improvement in patients with anaemia and thrombocytosis compared to the other treatment groups and both gold preparations were statistically superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Approximately 25% of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant reaction. Only 6% of patients on auranofin were withdrawn for untoward drug effect. The two gold preparations were similar in efficacy although auranofin was better tolerated.
Radiographic evaluation of erosion in rheumatoid arthritis: double blind study of auranofin vs placebo.
PA radiographs of hands and wrists from a randomized 6 month study of auranofin (AF) vs placebo followed by 6 months of open AF were scored for progression of erosive disease by 2 independent readers. The readers were blinded both to treatment and sequence (month 0 vs month 12) of the films. The results of our study demonstrate a reduction in the advancement of erosive disease during AF therapy compared to placebo.
The efficacy and safety of auranofin compared to placebo in rheumatoid arthritis.
This double-blind multicenter study compares the effect of adding auranofin (AF) 3 mg bid or placebo to patients already taking nonsteroidal antiinflammatory drugs for rheumatoid arthritis. The 242 patients who completed 3 months of therapy demonstrated that the group receiving AF responded better than those receiving placebo. Of the 144 patients who completed 6 months coded medication, the efficacy in the AF group was superior to the placebo group in several parameters including a reduction in the number of painful or swollen joints, grip strength, dropout rate, and global efficacy as judged by the evaluating physician. A significant lowering of the Westergren erythrocyte sedimentation rate and immunoglobulin levels was noted in the AF treated patients. This study includes data summarizing the difference between both groups with respect to on-therapy conditions and toxicity.
Auranofin versus placebo in the treatment of rheumatoid arthritis.
In a six-month, multicenter, double-blind study involving 340 patients, auranofin, 3 mg twice daily, was compared with placebo in the treatment of adult-onset rheumatoid arthritis. All patients were continued on a therapeutic regimen of salicylates and/or a newer nonsteroidal anti-inflammatory drug. Patients in both treatment groups who completed six months of therapy with coded medications showed significant improvement in the clinical features of rheumatoid arthritis (that is, number of tender and swollen joints, severity of pain, grip strength and duration of morning stiffness); however, the mean improvement was greater in the auranofin-treated group. Fifty-two percent of the auranofin-treated patients compared with 24 percent of the placebo-treated patients (p less than 0.05) were judged by their physician to have shown marked or moderate improvement. Only in the auranofin-treated patients was there significant improvement from baseline in the laboratory parameters of disease activity: erythrocyte sedimentation rate, IgA, IgG, and IgM. After at least three months of therapy, 30 percent (46 of 152) of the placebo-treated patients but only 9 percent (13 of 152) of the auranofin-treated patients (p less than 0.05) withdrew from coded medication due to insufficient therapeutic effect. Study medication was discontinued by 5 percent (eight of 152) of the auranofin-treated patients and 3 percent (four of 152) of the placebo-treated patients because of adverse therapy events (p = 0.24). This study demonstrates the efficacy of auranofin when added to salicylates and/or nonsteroidal anti-inflammatory drugs in the treatment of rheumatoid arthritis.
Options:
A: Auranofin showed no significant benefit over placebo in terms of tender joint scores, pain, and global assessments.
B: Auranofin demonstrated a statistically significant benefit over placebo for tender joint scores, pain, patient and physician global assessments, and ESR, but had higher withdrawal rates due to adverse reactions.
C: Auranofin was significantly less effective than placebo and had higher withdrawal rates due to adverse reactions.
D: Auranofin showed significant long-term benefits on health status and radiological progression compared to placebo.
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B
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67
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What was the conclusion regarding the clinical efficacy of nimodipine for the symptoms of dementia, including Alzheimer's disease, vascular dementia, and mixed Alzheimer's and vascular dementia? Please answer this question based on the information provided below:
Nimodipine in the treatment of old age dementias.
1. In a multicenter, placebo-controlled, double-blind clinical study in 178 elderly patients with cognitive decline, nimodipine, a calcium antagonist was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with 90 mg of nimodipine administered orally in divided doses for 12 weeks was significantly superior to an inactive placebo on all outcome measures including the Wechsler Memory Scale, the Mini Mental State Examination, the Global Deterioration Scale, the Sandoz Clinical Assessment Geriatric Scale, the Plutchik Geriatric Rating Scale, the Severity of Illness and Global Improvement Scales of Clinical Global Impression, and the Hamilton Psychiatric Rating Scale for Depression. 3. Adverse effects with nimodipine were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.
Calcium channel blocker nimodipine for primary degenerative dementia.
Short-term effects of the calcium channel blocker nimodipine (Bay-e-9736) in the management of primary degenerative dementia.
The etiology of Alzheimer's dementia (AD) is unknown, but several neurotransmitters, e.g., acetylcholine, have been implicated. Recently, the group of calcium channel antagonists have been reviewed for their potential neuropsychiatric applications. These agents are capable of enhancing cholinergic tone, neurofilament/microtubular stabilization, and regional perfusion rates. The following is a report of a randomized, double-blind, placebo-controlled, multicenter study of 227 AD patients treated with nimodipine, a 1.4 dihydropyridine derivative and calcium channel antagonist. The subgroup receiving active drug (30 mg t.i.d.) experienced a prophylactic benefit across eight measures over 12 treatment weeks when contrasted with the disease progression seen among placebo recipients. Calcium channel blockers as neurotransmitter modulators and/or via calcium's theoretical role in neurofibrillary tangles, proteolysis, or neurofilament formation may represent a therapeutic opportunity for the AD patient.
Divergent neuroprotective effects of nimodipine in PDD and MID provide indirect evidence of disturbances in Ca2+ homeostasis in dementia.
Evidence suggesting that increased cytotoxic Ca2+ concentrations due to disturbances of Ca2+ homeostasis are involved in neuronal deterioration in dementia has accumulated but has not yet been explicitly confirmed. Here we report of divergent neuroprotective effects of nimodipine, a Ca2+ channel blocker with high lipophilic properties, in primary degenerative dementia (PDD) and multiinfarct dementia (MID). Our clinical data show that nimodipine improves clinical symptomatology and cognitive functions in dementia significantly better than placebo but is more effective in PDD than in MID. This fact becomes explicitly apparent by comparison of the mean value differences of each of the 18 SCAG items between onset and termination of treatment in the two diagnostic groups. The divergent therapeutic response in PDD and MID suggests that the neuroprotective effects of nimodipine can not be due mainly to unspecific cognition enhancing mechanisms or vasodilatation of cerebral blood vessels but must primarily be the consequence of a direct activity in depolarized neuronal cells and of its ability to protect neuronal tissue from Ca2+ overload. Hence, we conclude that disturbances in Ca2+ homeostasis play an important role in the process of neuronal deterioration in dementia. Although we can not entirely rule out the possibility that pharmacological activities besides the modulation of neuronal Ca2+ influx contribute to the effects of nimodipine, from a clinical view our results provide indirect evidence of disturbances in Ca2+ homeostasis as one of the primary factors in the demential process. Our results further support the usefulness of nimodipine in the pharmacotherapy of age-related mental deficits.
The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia.
Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.
Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial.
In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.
Nimodipine in subcortical vascular dementia trial.
Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.
Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial.
BACKGROUND AND PURPOSE: Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD.
METHODS: 242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo.
RESULTS: 230 patients (121 nimodipine, mean age 75.2+/-6.1; 109 placebo, 75.4+/-6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production (P<0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; chi2 P<0.01) and Global Deterioration Scale (P<0.05). Dropouts and adverse events were all significantly more common among placebo than nimodipine patients, particularly cardiovascular (30 versus 13; RR, 2.26; 95% CI, 1.11 to 4.60) and cerebrovascular events (28 versus 10; RR, 2.48; 95% CI, 1.23 to 4.98), and behavioral disturbances requiring intervention (22 versus 5; RR, 3.88; 95% CI, 1.49 to 10.12). A worst-rank analysis, performed to correct for the effect of the high dropout rate in the placebo group, showed additional significant differences in favor of nimodipine in Set Test and MMSE total scores.
CONCLUSIONS: Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.
Options:
A: Nimodipine showed a significant improvement in cognitive function and overall clinical improvement in patients with dementia.
B: Nimodipine demonstrated no clear evidence of being an effective treatment for the symptoms of dementia.
C: Nimodipine was found to be harmful and worsened the symptoms of dementia in patients.
D: Nimodipine significantly improved the quality of life and functional autonomy in patients with dementia.
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B
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effectiveness of conventional systemic corticosteroid therapy in maintaining clinical remission in patients with Crohn's disease over a 24-month period? Please answer this question based on the information provided below:
European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment.
A multicenter double-blind study of the effectiveness of sulfasalazine and 6-methylprednisolone, alone and in combination, was conducted on 452 patients with Crohn's disease. One hundred sixty patients were previously untreated; 292 patients were previously treated. The Crohn's disease activity index (CDAI) was used to determine whether a patient had active (CDAI greater than or equal to 150, n = 215) or quiescent disease (CDAI less than 150, n = 237). Treatment of active disease consisted of high-dose 6-methylprednisolone, 6-methylprednisolone combined with 3 g of sulfasalazine, 3 g of sulfasalazine alone, or placebo, and lasted 6 wk. Patients in remission received maintenance doses of one of these drug regimens for periods of up to 2 yr. One hundred ninety-two patients completed the 2-yr study period. Results were evaluated using life-table analysis and outcome ranking. These methods showed 6-methylprednisolone to be the most effective drug in overall comparison of all patients (p less than 0.001); in previously treated patients (p less than 0.001); and in subgroups: active disease (p less than 0.001), only small bowel disease (p less than 0.05), and both small bowel and colon disease (p less than 0.05). Combination of 6-methylprednisolone and sulfasalazine was the most effective regimen in previously untreated patients (p less than 0.05) and when disease was localized in the colon (p less than 0.001). Sulfasalazine alone was least effective in overall comparison of all patients (p less than 0.05) and in all strata. Drug treatment was of no significant benefit to patients with quiescent disease. Continuous administration of low doses of 6-methylprednisolone, or the combination regimen, was beneficial in patients who responded initially to treatment of active disease. The addition of sulfasalazine, however, offered no advantage.
National Cooperative Crohn's Disease Study: results of drug treatment.
The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed.
Low dose steroids and clinical relapse in Crohn's disease: a controlled trial.
The long-term effect of prednisone in Crohn's disease has been examined in a double-blind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30% at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.
Options:
A: Conventional systemic corticosteroids significantly reduce the risk of relapse in Crohn's disease patients over 24 months.
B: Conventional systemic corticosteroids have no significant effect on the risk of relapse in Crohn's disease patients over 24 months.
C: Conventional systemic corticosteroids significantly increase the risk of relapse in Crohn's disease patients over 24 months.
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B
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69
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the overall effect of hydergine in patients with possible dementia, and what were the potential moderators of this effect? Please answer this question based on the information provided below:
Influence of treatment on symptomatology and correlated electroencephalographic (EEG) changes in the aged.
Combined hydrogenated alkaloids of ergot in mental and nervous disorders associated with old age.
[Dihydroergotoxine mesylate in the treatment of senile cerebral insufficiency. Result of a long-term multicenter double-blind clinical trial with a placebo].
Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)
A clinical trial comparing 'Hydergine' with placebo in the treatment of cerebrovascular insufficiency in elderly patients.
Ergoloid mesylates ('Hydergine') in the treatment of mental deterioration in the elderly: a 6-month double-blind, placebo-controlled trial.
A double-blind, placebo-controlled trial was carried out in 97 elderly patients with age-related mental deterioration to assess the efficacy of ergoloid mesylates in improving their symptoms. Patients were allocated at random to receive either 4.5 mg ergoloid mesylates per day or a matching placebo tablet and were followed-up for 6 months after the start of treatment. Clinical examinations were performed by the doctor, using the EACG rating scale (a French version of the Sandoz Clinical Assessment Geriatric scale), and by the nurse, using the NOSIE scale, when patients entered the trial and repeated after 2, 4 and 6 months. Changes in the factors (symptom groups) covered by these scales were subjected to statistical analysis. After 6-months' treatment, a statistically significant difference in favour of the ergoloid mesylates group was observed for cognitive deficits (p less than 0.05), anxiety and mood depression (p less than 0.01), unsociability (p less than 0.01), retardation (p less than 0.05) and irritability (p less than 0.001). Treatment was very well tolerated. It was also observed that there was a progressive increase in efficacy throughout the trial; this indicates that treatment with ergoloid mesylates in patients with mental deterioration should be long-term.
Lack of efficacy of hydergine in patients with Alzheimer's disease.
BACKGROUND: There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease.
METHODS AND RESULTS: Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument).
CONCLUSIONS: Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.
Ergoloid mesylates vs. Alzheimer's: the latest round.
Double-blind clinical and psychologic study of ergoloid mesylates (Hydergine) in subjects with senile mental deterioration.
A double-blind study of 24 weeks' duration was conducted to investigate the effects of ergoloid mesylates (Hydergine) on symptoms of senile mental deterioration. Fifty-eight residents of old people's homes were included in the trial. Thirty were treated with ergoloid mesylates and 28 with placebo, and the effects of treatment were determined by means of medical and psychological examinations. On the Sandoz Clinical Assessment Geriatric Scale, the group receiving ergoloid mesylates showed significant improvement in all items. The group receiving placebo showed slight deterioration. Psychological examination showed that no changes were observed for either group in quantitative psychometric test results, although qualitative aspects of performance such as attention and concentration did improve. There was a close correlation between improved cognitive function scores on the SCAG and improved evaluations of behavior during the psychological examinations. There were marked individual differences in the degrees of improvement.
Options:
A: Hydergine showed no significant effect compared to placebo, and the effect was not influenced by any moderators.
B: Hydergine showed a significant effect favoring its use compared to placebo, with greater effects associated with younger age and possibly higher doses.
C: Hydergine showed a significant effect favoring its use compared to placebo, but the effect was only influenced by the duration of the trial.
D: Hydergine showed no significant effect compared to placebo, but the effect was influenced by the diagnostic grouping of patients.
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B
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70
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the use of methotrexate as an addition to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids? Please answer this question based on the information provided below:
The role of methotrexate in the management of steroid-dependent asthma.
Severe asthma often requires high-dose corticosteroid therapy. However, steroid therapy is fraught with many side effects. There are conflicting reports in the literature regarding the role of methotrexate in reducing the steroid requirements of these patients. This study examined the role of low-dose methotrexate in the management of steroid-dependent asthma. Eleven subjects with stable steroid-dependent asthma were enrolled in a placebo-controlled double-blind crossover trial. Patients received methotrexate, 15 mg/wk, or placebo each for two 12-week periods. There was significant improvement of pulmonary function and reduction of prednisone requirement in both placebo and methotrexate treatment periods. However, methotrexate was not superior to placebo. Only 3 of 11 patients responded to methotrexate. Although low-dose methotrexate therapy may have a role in a small select group of steroid-dependent asthmatics, it provided no additional benefit overall.
Methotrexate in the treatment of steroid-dependent asthma.
A double-blind, placebo-controlled, crossover study was designed to compare steroid requirements between placebo and methotrexate (MTX) treatment in subjects with corticosteroid-requiring asthma. Subjects began with a steroid taper and then were randomized to a 3-month trial of drug or placebo therapy. Subjects received 15 mg of MTX a week or identical placebo. A 1-month washout period was completed before the crossover trial. Symptom scores, peak flow rates, spirometry, and beta-agonist frequency were closely monitored. Ten subjects completed the study. The average dose of prednisone during the placebo-treatment period was 11.97 mg/day compared to 8.37 mg/day while subjects were taking MTX. This was a 30% reduction in daily steroid requirement (p less than 0.01). Symptom scores and spirometry did not differ between the crossover trials, and overall clinical status was not altered. Complications from MTX were mild and included anorexia, alopecia, and stomatitis. All complications resolved with dose reduction or when MTX was stopped at the end of the study. No subjects withdrew from the study because of MTX complications. Low-dose MTX significantly reduced the steroid requirement in this group of subjects with steroid-dependent asthma. This reduction in steroid requirement was obtained without altering clinical status and without significant complication.
Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double-blind, placebo-controlled study.
OBJECTIVE: To determine the effect of low-dose methotrexate in asthmatic patients on steroid use, asthma symptom scores, pulmonary function, airway reactivity, blood cellular components, and immunoglobulin E levels.
DESIGN: A randomized, double-blind, parallel, placebo-controlled, 13-week clinical trial with follow-up of patients in an open trial of methotrexate at the conclusion of the double-blind study.
SETTING: An asthma care outpatient clinic.
PATIENTS: From February 1988 to March 1990, 19 patients with severe, steroid-dependent asthma were enrolled in the study. Two of these patients were excluded from analysis.
INTERVENTIONS: Patients were administered methotrexate or placebo intramuscularly, to assure complete absorption, once weekly during the 13-week study.
RESULTS: Patients on methotrexate and placebo both significantly decreased their steroid dose by 39.6% (95% CI, 25.1% to 54.1%, P = 0.001) and 40.2% (CI, 17.9% to 67.4%, P = 0.003), respectively. Pulmonary function did not differ significantly between the methotrexate and placebo groups. In addition, airway reactivity and symptom scores were unchanged on methotrexate or placebo. No significant toxicities were seen during the course of the 13-week blinded study, but one patient on methotrexate and prednisone in the follow-up period developed Pneumocystis carinii pneumonia and died. Despite continuing methotrexate for up to 1 year, and increasing methotrexate to 30 mg weekly, no significant benefit of methotrexate on asthma control could be shown.
CONCLUSION: Our study does not support the use of methotrexate in the treatment of severe asthma.
Controlled trial of methotrexate in patients with severe chronic asthma.
The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2-28) mg.day-1, and the mean dose of inhaled steroids administered was 2.3 (1.6-3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg.day-1 during the last 2 placebo weeks but only 7.9 mg.day-1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.
Short term effect of methotrexate in severe steroid-dependent asthma.
The steroid-sparing capacity of methotrexate in asthmatics is still being debated. The present study was undertaken to evaluate the effect of low-dose methotrexate on steroid consumption in patients with severe asthma, who require very high doses of systemic corticosteroids. We conducted a randomized, double-blind, parallel clinical trial in 24 patients with long-standing asthma. After a 3-week run-in period, patients received a 16-week course of either 15 mg of oral methotrexate weekly or matched placebo in addition to their previous asthma therapy. The daily steroid dose (at run-in 30 +/- 14 mg/day in the methotrexate group; 25 +/- 9 mg/day in the placebo group (NS)) decreased by 24% in the methotrexate group (p < 0.01) and by 5% in the placebo group (NS) during weeks 9-16 of the treatment period when compared with run-in values. However, there was no difference in steroid consumption between the two groups at any time. We conclude that in patients with severe asthma who require very high doses of systemic corticosteroids, short-term treatment with methotrexate allows only a marginal steroid reduction. Our study does not support the use of methotrexate as a steroid-sparing agent in asthmatics.
Methotrexate in the treatment of corticosteroid-dependent asthma. A double-blind crossover study.
To test our previous observation that methotrexate reduces corticosteroid requirements of patients with severe asthma, we studied 14 patients with corticosteroid-dependent bronchial asthma in a 24-week randomized double-blind crossover trial comparing a low dosage of methotrexate (15 mg per week) with placebo. At base line the mean dosage of prednisone was 173.5 mg per week (range, 70 to 420). On the average, 36.5 percent less prednisone was required when patients received methotrexate than when they received placebo (P = 0.01). Measurement of forced vital capacity and forced expiratory volume in one second showed that there was no deterioration in the condition of patients in whom the dosage of prednisone was reduced. The patients' subjective assessment of breathing ability indicated significant improvement (P = 0.01). The adverse effects of methotrexate were limited to transient nausea in three patients and an evanescent rash in one patient. Nine patients are still receiving methotrexate 3 to 10 months after the study's conclusion. The dosages of steroids have been further reduced in each of these patients, and prednisone has been discontinued in four. We conclude from this preliminary study that the use of methotrexate allows a significant reduction in the use of corticosteroids in patients with severe asthma without deterioration of pulmonary function.
Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma.
69 patients with steroid-dependent asthma (mean daily prednisolone dose 14.2 [SD 6.1] mg) took part in a randomised, double-blind, placebo-controlled study of 24 weeks' treatment with methotrexate 15 mg weekly. The patients were seen every 4 weeks by the same physician, who reduced the daily prednisolone dose by 2.5 mg if the daily diary card variables and measurements of lung function were unchanged or improved. All other treatment remained unchanged. After 24 weeks of treatment the prednisolone dose had been reduced by a significantly greater proportion in the methotrexate than in the placebo group (50% vs 14%) and the reduction was not sustained after the study treatment stopped. There were substantial abnormalities in liver function tests in 5 of the 38 patients taking methotrexate.
Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma.
69 patients with steroid-dependent asthma (mean daily prednisolone dose 14.2 [SD 6.1] mg) took part in a randomised, double-blind, placebo-controlled study of 24 weeks' treatment with methotrexate 15 mg weekly. The patients were seen every 4 weeks by the same physician, who reduced the daily prednisolone dose by 2.5 mg if the daily diary card variables and measurements of lung function were unchanged or improved. All other treatment remained unchanged. After 24 weeks of treatment the prednisolone dose had been reduced by a significantly greater proportion in the methotrexate than in the placebo group (50% vs 14%) and the reduction was not sustained after the study treatment stopped. There were substantial abnormalities in liver function tests in 5 of the 38 patients taking methotrexate.
Comparison of oral pulse methotrexate with placebo in the treatment of severe glucocorticosteroid-dependent asthma.
BACKGROUND: This study compared the efficacy of weekly oral administration of methotrexate and placebo in treatment of 24 subjects with chronic glucocorticosteroid-dependent asthma.
METHODS: The 33-week randomized, double-blind, placebo-controlled crossover trial compared once weekly 15 mg doses of methotrexate with placebo. At the time of entry, the subjects' mean dosage of prednisone was 23.8 mg/day (range, 12.5 to 85 mg) and glucocorticosteroid therapy had been used continuously for a mean duration of 78 months (range, 5 to 360 months).
RESULTS: Of the 21 subjects who completed the study, 13 tolerated lower daily prednisone doses during methotrexate treatment compared with placebo. When treated with methotrexate, subjects required 14.2% less prednisone than when treated with placebo (p = 0.0447), their subjective symptom scores improved 21.4% (p < 0.05), and mean forced expiratory volume in 1 second values tended to improve. Mean serum theophylline levels did not change significantly between the methotrexate and placebo arms of the study. Adverse effects were minimal, with nausea and headache occurring twice as often during methotrexate therapy compared with placebo.
CONCLUSION: Short-term, low-dose, pulse therapy with orally administered methotrexate results in a decrease in the daily glucocorticosteroid requirement in a majority of subjects with severe asthma and is accompanied by improvement in subjective symptom scores without unacceptable side effects or deterioration of pulmonary function.
Methotrexate in the management of severe steroid dependent asthma.
AIMS: This study was designed to assess the efficacy of low dose methotrexate, 15 mg weekly, as a steroid-sparing agent in asthmatic patients requiring long-term oral prednisone treatment.
METHODS: The study was a randomised, double blind, placebo controlled, cross over study of 48 weeks duration. Eleven patients with severe steroid-dependent asthma were included. A successful outcome was defined as a reduction in mean prednisone requirements of 7 mg daily compared to baseline requirements, during active treatment.
RESULTS: Two patients were required to be withdrawn owing to methotrexate-related adverse effects. The mean prednisone dose for patients who completed the study was 14.4 mg per day (95% CI; 13.6, 15.1) during active treatment, and 12.9 mg per day (95% CI: 12.2, 13.6) during placebo treatment (NS). Only one patient reduced his individual dose requirements by more than 7 mg per day, whereas in three patients prednisone requirements actually increased during active treatment. There were no significant differences in symptom scores, pulmonary function data, and exacerbations between active and placebo treatments.
CONCLUSION: No significant steroid-sparing effect was obtained using low dose methotrexate in this study. This negative outcome may be attributable to the small population of patients studied, low baseline FEV1, and the omission of a steroid minimisation run-in period. Our results highlight the importance of careful patient selection and a painstaking approach in the management of patients with steroid-dependent asthma.
Comparison of methotrexate 30 mg per week with placebo in chronic steroid-dependent asthma: a 12-week double-blind, cross-over study.
Methotrexate has been shown to have a steroid-sparing effect in chronic steroid-dependent asthmatics at a dose of 15 mg week-1. The aim of this study was to investigate the steroid-sparing activity and adverse events profile of methotrexate 30 mg week-1 in severe steroid-dependent asthma. Eighteen patients who had required 10-50 mg week-1 prednisolone for at least 6 months were asked to participate in a randomized, double-blind, placebo-controlled cross-over study lasting 24 weeks. Daily diary cards of symptoms, peak expiratory flow rate and medication requirements were kept and the patients attended for a chest X-ray, spirometry, lung volumes and gas transfer at commencement and after each 12-week treatment period. Every 3 weeks, adverse events were noted and blood taken for full blood count, urea and electrolytes and liver function tests. Twelve patients completed the trial. Withdrawals were due to non-compliance in two patients, pneumonia in two patients, depression in one patient (on placebo) and severe nausea in one patient. Adverse events were common, probably as a consequence of the higher dosage. Prednisolone requirements were not significantly reduced on methotrexate. Lung function improved on methotrexate with a significant rise in maximal mid-expiratory flow rate and a trend towards improvement in FEV1.
Options:
A: Methotrexate significantly reduced the daily dose of oral corticosteroids and improved lung function without notable adverse effects.
B: Methotrexate had a small steroid sparing effect, but the reduction in daily steroid use was not large enough to reduce steroid-induced adverse effects, and it was associated with common adverse effects such as hepatotoxicity.
C: Methotrexate had no effect on the daily dose of oral corticosteroids or lung function and was associated with severe adverse effects.
D: Methotrexate significantly improved lung function and reduced the daily dose of oral corticosteroids, with minimal adverse effects.
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B
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71
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the findings regarding the use of thioridazine in the treatment of dementia in terms of efficacy, cognitive outcomes, and safety? Please answer this question based on the information provided below:
A comparison of chlormethiazole and thioridazine in agitated confusional states of the elderly.
Chlormethiazole and thioridazine were found to be equally effective in the management of the agitational component of agitated confusional states in the elderly. Confusion and nocturnal awakening were found to be controlled more effectively with chlormethiazole than with thioridazine. Chlormethiazole treatment also resulted in significant reductions in physical disability as assessed by the Clifton Behaviour Rating Scale. A greater incidence of adverse effects was associated with thioridazine treatment.
Behavioral symptoms in dementia: community-based research.
Efficacy of antipsychotic medications in behaviorally disturbed dementia patients.
This study compared the therapeutic efficacy of thioridazine, loxapine, and a placebo in the treatment of behavioral disturbances in nursing home patients with dementia. Antipsychotic medications were effective for the specific behavioral problems of anxiety, excitement, emotional lability, and uncooperativeness. Subjects with the most severe symptoms at baseline assessment derived the greatest benefit from treatment. Sedation, extrapyramidal symptoms, and decreased blood pressure were common side effects among patients treated with the antipsychotic drugs. The authors conclude that antipsychotic medication has a definite but limited therapeutic role in the treatment of behavioral disturbances in nursing home patients with dementia.
Alleviating agitation, apprehension, and related symptoms in geriatric patients: A double-blind comparison of a phenothiazine and a benzodiazepien.
A four-week, double-blind study compared the effectiveness of thioridazine and diazepam in 40 geriatric patients with various symptoms of senility. Patients' progress was evaluated with the Hamilton Anxiety Rating Scale, a Modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), a global rating of degree of illness, and a global rating of degree of overall change. The data indicate that thioridazine was superior to diazepam inrelieving troublesome symptoms of senility.
Video methodology for research in psychopathology and psychopharmacology: Rationale and application.
Comparison of thioridazine and diazepam in the control of nonpsychotic symptoms associated with senility: double-blind study.
Multicenter study comparing thioridazine with diazepam and placebo in elderly, nonpsychotic patients with emotional and behavioral disorders.
Thioridazine was compared with placebo or diazepam or both in 610 elderly, nonpsychotic inpatients in geriatric wards of state hospitals or nursing homes. All patients manifested disruptive and difficult-to-manage behavior that interfered with adjustment to their environment and with proper care and treatment of their medical and emotional problems. Target symptoms such as agitation, anxiety, tension, apprehension, depressed mood, and sleep disturbances showed consistently marked improvement throughout the four-week study, as measured by the modified Hamilton Anxiety Scale, the modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and global ratings. Significantly greater improvement on all measures was achieved with thioridazine than with placebo. In addition, greater improvement in the majority of symptoms assessed by the Hamilton Anxiety Scale and NOSIE were seen in patients who received thioridazine than in those given diazepam.
Options:
A: Thioridazine is highly effective in controlling symptoms, improves cognitive outcomes, and has fewer adverse effects compared to other treatments.
B: Thioridazine reduces anxiety symptoms but does not significantly affect clinical global change, and it has a trend for higher adverse effects compared to placebo.
C: Thioridazine shows significant improvement in both anxiety and cognitive outcomes with fewer adverse effects compared to other neuroleptics and sedatives.
D: Thioridazine is ineffective in controlling symptoms, worsens cognitive outcomes, and has significantly more adverse effects compared to placebo and other treatments.
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B
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72
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness of artemisinin drugs compared to quinine in treating severe or complicated falciparum malaria in adults and children? Please answer this question based on the information provided below:
Comparison of rectal artemisinin with intravenous quinine in the treatment of severe malaria in Ethiopia.
OBJECTIVE: To compare the clinical efficacy and safety of artemisinin suppository with quinine injection.
DESIGN: Comparative open randomised study.
SETTING: A government regional referral hospital in Ethiopia.
SUBJECTS: Sixty five adult patients of both sexes: 32 for artemisinin and 33 for quinine with complicated severe falciparum malaria.
MAIN OUTCOME MEASURES: Therapeutic responses and adverse reactions.
RESULTS: The clinical and laboratory data in both groups of patients on admission were comparable. The parasite clearance time (PCT), fever subsidence time (FST) and coma resolution time (CRT) were shorter in the artemisinin treated group. There was no significant different in the parasitological cure rates in both arms of treatment. No correlation was observed between the initial parasite density and PCT or FST in both groups of treatment. Mortality rates were similar both in the artemisinin and quinine groups. The common adverse effects observed in most patients receiving quinine, in an increasing order of occurrence were; vomiting, dizziness, hypoglycaemia and tinnitus, which were all relatively rare with artemisinin. Some patients treated with artemisinin showed tenesmus which was not observed in any patient treated with quinine.
CONCLUSION: The rectal artemisinin is more efficacious and safer than the intravenous quinine. Thus, artemisinin may be considered a potential drug which can replace quinine in the treatment of severe malaria in Ethiopia provided it is made available at affordable prices.
Artemether in the treatment of multiple drug resistant falciparum malaria.
Artemether has the potential to be an alternative antimalarial for multiple drug resistant falciparum malaria. However, it has been associated with high recrudescent rates which may be due to incorrect dosage regimens. The dosage regimens are varied from country to contry. We have carried out a comparative study of two dosage regimens, ie 480 mg and 600 mg total dose given over 5 days in uncomplicated and severe falciparum malaria. 167 patients were included in the study, 61 with acute uncomplicated falciparum malaria and 106 with severe malaria. All patients showed a good initial response. The difference in total dose had no effect on the parasite or fever clearance time (PCT or FCT). However, the severity of the disease did have some influence of these times. The PCT and FCT from either regimen of uncomplicated malaria were significantly faster than those of severe malaria (p < 0.005 and = 0.05, respectively). The cure rate seems to have some correlation with the amount of drug given and severity of the disease. The cure rates in uncomplicated malaria were 84 and 92%, respectively, for 480 mg and 600 mg. In severe malaria the cure rates dropped to 65 and 76%, respectively, for 480 and 600 mg. We conclude that artemether can be considered as an alternative antimalarial for multiple drug resistant falciparum malaria. However, the cure rate of severe falciparum malaria in this study is not considered satisfactory in areas with multiple drug resistant falciparum malaria. Further studies are needed to assess the curative efficacy with different dosage regimens.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria.
Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated.
An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria.
An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes.
A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria.
BACKGROUND: Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine.
METHODS: We conducted a randomized, double-blind trial in 560 adults with severe falciparum malaria. Two hundred seventy-six received intramuscular quinine dihydrochloride (20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours), and 284 received intramuscular artemether (4 mg per kilogram followed by 2 mg per kilogram every eight hours). Both drugs were given for a minimum of 72 hours.
RESULTS: There were 36 deaths in the artemether group (13 percent) and 47 in the quinine group (17 percent; P = 0.16; relative risk of death in the patients given artemether, 0.74; 95 percent confidence interval, 0.5 to 1.11). The parasites were cleared more quickly from the blood in the artemether group (mean, 72 vs. 90 hours; P < 0.001); however, in this group fever resolved more slowly (127 vs. 90 hours, P < 0.001), the time to recovery from coma was longer (66 vs. 48 hours, P = 0.003), and the hospitalization was longer (288 vs. 240 hours, P = 0.005). Quinine treatment was associated with a higher risk of hypoglycemia (relative risk, 2.7; 95 percent confidence interval, 1.7 to 4.4; P < 0.001), but there were no other serious side effects in either group.
CONCLUSIONS: Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults.
Preliminary report: a comparative clinical trial of artemether and quinine in severe falciparum malaria.
Twenty-six patients with severe falciparum malaria were randomized to be treated with quinine or artemether. Twelve patients received quinine at the standard dose and fourteen patients received artemether intramuscularly at a total dose of 640 mg over 7 days. The patients were kept in the hospital for at least 7 days. Peripheral smear was performed 6-hourly until there was no parasitemia, then daily until discharged. Adverse effects were monitored through physical examination, laboratory findings and questionnaires. Laboratory examination was performed on admission, day 2, day 4 weekly until discharged. The patients in both groups were comparable in age, body weight, admission parasitemia, hemoglobin and white blood cell count. The survival rates were 93% and 58% in artemether and quinine groups, respectively (p = 0.052 at 95% confidence, using Fisher's exact test). The parasite and fever clearance times, and the time taken to gain consciousness in cerebral malaria patients were not significantly different between the two groups. Adverse effects in the quinine group consisted of dizziness and vertigo which were found in 4 patients. No adverse effects were noticed in the artemether group. This preliminary report suggests that artemether is a good alternative drug for severe falciparum malaria and seems to be better than quinine regarding survival rate and side effects. Confirmation of these findings in a larger study size is needed.
Artemether 5 versus 7 day regimen for severe falciparum malaria.
Twenty-eight male Thai patients with severe falciparum malaria were randomized to receive either artemether for a 5 (300 mg initial dose followed by 100 mg for another 4 days) or a 7 days regimen (160 mg initial dose, followed by 80 mg daily for another 6 days). Thirteen patients received a 5 day regimen and 15 received 7 day regimen. The follow-up period was 28 days. The patients in both groups were comparable in age, body weight, admission parasitemia, hematocrit and white cell count. There were 4 patients in each group who presented with cerebral malaria. The median values of parasite and fever clearance times (PCT and FCT) in the 5 and 7 days regimens were 52 vs 60 hours, and 85 vs 68 hours, respectively. There were 8 and 4 patients, respectively who had recrudescence during days 15 to 25. The cure rates were 38% (95% CI = 14-68%) and 73% (95% CI - 50-96%), respectively for 5 and 7 day regimens. None died in either group. No patients in either group had neurological sequelae after recovery of consciousness. Clinically adverse effects in either group were transient pain at the site of injection. No drug related biochemical or ECG changes were noted in either group. The duration of treatment is the determinant of the cure rate; however, the duration of even 7 days still resulted in high recrudescence rate. It may be necessary to combine artemether with other longer half-life antimalarials to improve the cure rate.
Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand.
One hundred and two Thai patients with severe falciparum malaria (92 males and 10 females) were allocated at random to receive either the standard regimen of quinine infusion (52 cases) or intramuscular artemether (50 cases). The patients in both groups had comparable admission clinical and laboratory data. Artemether gave a better survival rate (87.2% vs. 63.3%) and parasite clearance time (54 vs. 78 h) than quinine. Fever clearance times (79 h vs. 84 h) and time to recovery of consciousness (48 h in both groups) were comparable. Previous treatment with quinine or mefloquine had no influence on treatment outcome. The most common adverse effect in patients treated with quinine was tinnitus. Two patients had severe hearing impairment which resolved within 1 week after the end of treatment. Mild, transient pain was noted at the injection site of artemether but no abscess formed. QTc wave prolongation was seen in most patients receiving quinine; however, no arrhythmia was observed despite the high concentration of quinine in some patients who had received quinine before admission. Complications developed in 7 survivors in each treatment group. No patient in the artemether group had neurological sequelae after recovery of consciousness, but 2 in the quinine group had left facial palsy and one had a myasthenia gravis-like syndrome. No patient died with complications in he artemether group, but 7 died with pulmonary complications in the quinine group.
A comparative clinical trial of sequential treatments of severe malaria with artesunate suppository followed by mefloquine in Thailand.
Sixty-three patients with severe falciparum malaria were randomly administered one of the two regimens of a sequential combination of artesunate suppository followed by an oral mefloquine tablet. Thirty-two patients received artesunate suppositories (200 mg/capsule) given rectally at 0, 4, 8, 12, 24, 36, 48, and 60 hr (total = 1,600 mg: Group I). Thirty-one patients received the same artesunate suppositories given rectally at 0, 12, 24, 36, 48, and 60 hr (total = 1,200 mg: Group II). Both regimens were followed by two doses of oral mefloquine, 750 mg given at 72 hr and 500 mg at 84 hr. Patient baseline characteristics were comparable in the two groups. All patients were admitted for 28 days to the Bangkok Hospital for Tropical Diseases to assess efficacy, tolerability, and delayed neuropsychiatric effects. The mean [SD] parasite clearance time was significantly shorter in Group I than Group II (47.3 [12.4] hr versus 55.3 [17.4] hr; P = 0.05) and the rate of parasite reduction was significantly faster in Group I (P = 0.05, by log-rank test). Mean [SD] fever clearance times were similar in the two Groups (71.1 [41.2] hr and 76.9 [47.9] hr, respectively). Twenty-two patients with unrousable coma on admission (median Glasgow Coma Score = 9) regained consciousness after 1-4 days. No deaths occurred. Sixty of sixty-three patients were parasitologically and clinically cured within 3-4 days of treatment. Three patients (5%) with deteriorating conditions required rescue treatment (one patient in Group I was administered intravenous artesunate, and two patients in Group II required two extra doses of suppository). No patients had major adverse drug effects. The cure rates at 28 days of follow-up in Group I were 96% (26 of 27 patients) and 89% (24 of 27 patients) in Group II. Artesunate suppository followed by mefloquine was well tolerated and effective. In severe malaria, the sequential treatment is a suitable alternative treatment to parenteral drugs. Further studies in a larger number of patients under field conditions are required.
An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children.
We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open randomized clinical trial in Kenya. Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether (3.2 mg/kg loading dose followed by 1.6 mg/kg daily) or intravenous quinine (20 mg/kg loading dose followed by 10 mg/kg every 8 h). Both drugs were well tolerated and no significant adverse effect was observed. Parasite clearance times (50% and 90%) were shorter in patients treated with artemether (median times [h], with interquartile ranges in brackets, were: 50%, 7.3 [4.2-12.4] vs. 15.5 [9-22]; 90%, 16.9 [13.2-25] vs. 28.5 [22-35]; P < 0.0001). The total mortality in 160 children with cerebral malaria was 16.25%, with no overall significant difference between the 2 treatment groups. In a subgroup of children with respiratory distress, mortality was higher in those treated with artemether (43.7% vs. 11.1%, P < 0.05). The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups. We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children.
Comparative efficacy of intramuscular artemether and intravenous quinine in Nigerian children with cerebral malaria.
The efficacy of a 5-day treatment with intramuscular artemether (3.2-mg/kg loading dose followed by 1.6 mg/kg daily) was compared to that of the standard 7-day treatment with quinine (20-mg/kg loading dose followed by 10 mg/kg every 8 h) in a randomised clinical trial including 103 children aged 12-60 months with cerebral malaria between 1994 and 1996. No statistical difference of immediate efficacy was found between the two treatments. There were 11 (20%) deaths in the artemether group and 14 (28%) in the children who received quinine. The respective artemether versus quinine median fever clearance times (h) were 39 (interquartile ranges [IQ] 30-54) vs. 48 (IQ 30-60), and parasite clearance 42 (IQ 24-60) vs. 36 (IQ 30-48). However, one patient who received artemether had a recrudescence on day 14, which was successfully treated with sulphadoxine-pyrimethamine. Times to recovery from coma were 24 h (IQ 18-45) and 33 h (IQ 19-57), respectively. The occurrence of transient neurological sequelae including motor disabilities, cortical blindness, and afebrile seizures was also similar in the two groups. No adverse reactions to the two drugs were recorded during the study period. Artemether represents an important option in the management of cerebral malaria in Nigeria especially in rural areas where facilities for intravenous administration may not yet be optimal.
Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria.
Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P < 0.0001). Both artemisinin and artesunate were very well tolerated, but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.
Randomized comparison of intramuscular artemether and intravenous quinine in adult, Melanesian patients with severe or complicated, Plasmodium falciparum malaria in Papua New Guinea.
An open-label, randomized, controlled trial was used to compare the safety and efficacy of intramuscular artemether (a loading dose of 3.2 mg/kg, followed by 1.6 mg/kg daily for 4 days) and intravenous quinine (a loading dose of 20 mg quinine dihydrochloride/kg, followed first by 10 mg/kg every 8 h, each injection taking 4 h, for at least 48 h, and then oral quinine for a total of 7 days) in the management of strictly defined severe/complicated malaria in Melanesian adults. Four (12%) of the 33 patients who enrolled and completed follow-up died (one of the 15 who received artemether and three of the 18 who received quinine). Overall, cerebral malaria was uncommon (6%) whilst jaundice was common (76%). The time taken to clear 50% of parasites was less in those treated with artemether (median = 8 h; range = 2-24 h) than in the patients given quinine (median = 14 h; range = 2-25 h; P = 0.05). Temperature defervescence was also quicker in those treated with artemether (median = 32 hours; range = 20-112 h) than in those in the quinine group (median = 48 h; range = 28-88 h; P = 0.034). Hypoglycaemia was not observed in any patient treated with artemether but complicated therapy in 11 (79%) of the 14 patients given quinine who had not had pre-treatment spontaneous hypoglycaemia. No serious adverse effects were attributable to artemether. The Plasmodium falciparum infections observed during the 1 month of follow-up, in three patients who had received artemether and two who had been given quinine, were probably due to recrudescence. Plasmodium vivax parasitaemias were also observed during follow-up, in one or two patients in each treatment group. Artemether appears safe in Melanesian adults and is probably as effective as intravenous quinine in the treatment of severe or complicated falciparum malaria.
Intramuscular artemether vs intravenous quinine: an open, randomized trial in Malawian children with cerebral malaria.
OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children.
METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here.
RESULTS: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses.
CONCLUSION: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.
A trial of artemether or quinine in children with cerebral malaria.
BACKGROUND: Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance. Artemether is a new antimalarial agent that clears parasites from the circulation more rapidly than quinine, but its effect on mortality is unclear.
METHODS: We conducted a randomized, unblinded comparison of intramuscular artemether and intramuscular quinine in 576 Gambian children with cerebral malaria. The primary end points of the study were mortality and residual neurologic sequelae.
RESULTS: Fifty-nine of the 288 children treated with artemether died in the hospital (20.5 percent), as compared with 62 of the 288 treated with quinine (21.5 percent). Among the 418 children analyzed at approximately five months for neurologic disease, residual neurologic sequelae were detected in 7 of 209 survivors treated with artemether (3.3 percent) and 11 of 209 survivors treated with quinine (5.3 percent, P = 0.5). After adjustment for potential confounders, the odds ratio for death was 0.84 (95 percent confidence interval, 0.53 to 1.32) in the artemether group, and for residual neurologic sequelae, 0.51 (95 percent confidence interval, 0.17 to 1.47). There were fewer local reactions at the injection site with artemether than with quinine (0.7 percent vs. 5.9 percent, P = 0.001).
CONCLUSIONS: Artemether is as effective as quinine in the treatment of cerebral malaria in children.
Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam.
One hundred and seventy five Vietnamese adults with severe and complicated malaria admitted to a rural district hospital were entered into an open randomized comparative study to compare 4 treatment regimens based on artemisinin and its derivatives. The median time of defervescence was 48 h (95% confident interval [CI] 38-58 h) in those given intramuscular (i.m.) artemether, 42 h (95% CI 36-48 h) in those given artemisinin suppositories, 36 h (95% CI 30-42 h) in those receiving artesunate (i.m.) and 30 h (95% CI 18-42 h) in those receiving intravenous artesunate (P = 0.13). The respective median parasite clearance times were 30 h (95% CI 26-34 h), 30 h (95% CI 24-36 h), 24 h (95% CI 15-33 h), and 24 h (95% CI 15-33 h) (P = 0.30); the median times for recovery of consciousness were 47 h (95% CI 31-63 h), 24 h (95% CI 18-30 h), 30 h (95% CI 18-42 h), and 24 h (95% CI 4-44 h) (P = 0.18); and the mortality rates were 11.1%, 17.6%, 10.2% and 16.6%, respectively (P = 0.64). There was no significant difference in efficacy between the 4 treatments.
Comparison of artemether and chloroquine for severe malaria in Gambian children.
Artemether is an oil-soluble methyl ether of artemesinin (qinghaosu). It has been studied extensively in China, where it has been shown to be rapidly effective in severe falciparum malaria. Nearly all the patients studied previously were adults. We have investigated the efficacy of artemether in children with moderate or severe falciparum malaria. In the preliminary study of moderately severe malaria, 30 Gambian children were randomised in pairs to receive either intramuscular artemether (4 mg/kg loading dose followed by 2 mg/kg daily) or intramuscular chloroquine ('Nivaquine') 3.5 mg base/kg every 6 h. Both drugs were well tolerated and rapidly effective. The times to parasite clearance were significantly shorter in the artemether recipients (mean 36.7 [SD 11.3] vs 48.4 [16.8] h, p less than 0.05). 43 children with severe malaria were then randomised to receive intramuscular treatment with the same regimens of artemether (n = 21) or chloroquine (n = 22) as used in the preliminary study. 8 children (19%) died. There were no significant differences between the two groups in the clinical, haematological, biochemical, or parasitological measures of therapeutic response in survivors and there was no evidence of local or systemic toxicity. Despite similar parasite counts on admission, clearance times overall were longer in severe malaria than in moderate malaria. Artemether is a well tolerated and rapidly effective parenteral treatment for severe malaria in children, and would be especially valuable in areas with chloroquine-resistant P falciparum.
Comparison of combinations of parenteral artemisinin derivatives plus oral mefloquine with intravenous quinine plus oral tetracycline for treating cerebral malaria.
A total of 141 cases of strictly defined cerebral malaria were studied in a controlled trial of three regimens: (1) intramuscular artemether plus oral mefloquine, (2) intravenous artesunate plus oral mefloquine, and (3) intravenous quinine (with or without an initial loading dose) plus oral tetracycline. The overall mortalities in each group were 14%, 8.3% and 34.3% respectively. The average parasite clearance time was 27.30 +/- 19.62 hours in regimen 1, 41.84 +/- 17.55 hours in regimen 2, and 47.30 +/- 21.95 hours in regimen 3. No recrudescence was observed in regimens 1 and 2, but 12.1% recrudesced in the third.
Options:
A: Artemisinin drugs were associated with better survival rates and faster parasite clearance from the blood compared to quinine.
B: Artemisinin drugs were associated with worse survival rates and slower parasite clearance from the blood compared to quinine.
C: Artemisinin drugs showed no difference in survival rates or parasite clearance from the blood compared to quinine.
D: Artemisinin drugs were associated with better survival rates but slower parasite clearance from the blood compared to quinine.
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A
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73
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings regarding the clinical effects of newer atypical antipsychotic drugs compared to clozapine for schizophrenia? Please answer this question based on the information provided below:
Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial.
1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.
Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial.
1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.
Randomized, double-blind, controlled trial of risperidone versus clozapine in patients with chronic schizophrenia.
This study compares the antipsychotic efficacy and the tolerability of risperidone and clozapine in patients with schizophrenia. Patients were randomized to double-blind treatment with risperidone, 4 mg (N = 20), risperidone, 8 mg (N = 19), or clozapine, 400 mg (N = 20), daily for 28 days. Efficacy was assessed by improvement of psychotic symptoms, measured on the Brief Psychiatric Rating Scale, and Clinical Global Impression. The tolerability was assessed by the Simpson and Angus scale for extrapyramidal side effects (EPS), the Association for Methodology and Documentation in Psychiatry (AMDP) scale for somatic side effects, spontaneous reports of adverse events, clinical laboratory assessments, and vital signs. All treatments reduced psychotic symptoms. The global tolerability was significantly better in the risperidone than in the clozapine-treated patients (p < 0.01). There were no differences between treatments on the AMDP scale. The most frequent spontaneously reported adverse effects were dizziness, fatigue, accommodation disturbance, and EPS in all treatment groups and increased salivation, mainly in the clozapine-treated patients. Although there were no changes in vital signs during risperidone treatment, clozapine was associated with a mean reduction in heart rate of 10 beats/minute. Risperidone tolerability at endpoint was classified as "very good" by 60 and 47% of patients treated with risperidone, 4 and 8 mg daily, respectively; the corresponding figure in clozapine-treated patients was 30%. The results suggest that risperidone is at least as effective as an antipsychotic as clozapine, providing a valuable new approach for the treatment of schizophrenia.
The tolerability and efficacy of the atypical neuroleptic remoxipride compared with clozapine and haloperidol in acute schizophrenia.
Remoxipride and clozapine are new neuroleptics that are thought to be superior to the substances in use by their efficacy and tolerance. At the University Clinic of Psychiatry in Düsseldorf a double-blind study with 54 patients diagnosed as schizophrenic in accordance with DSM-III was conducted to record the influence of the neuroleptics remoxipride, clozapine and haloperidol on schizophrenic psychosis. The schizophrenic symptoms were rated by the AMDP-system (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie), Brief Psychiatric Rating Scale and the Clinical Global Impression on days 0, 7, 14, 21 and 28 of treatment to evaluate the degree of change in psychopathology. The tolerance of the neuroleptic treatment was checked by the doctor's overall impression and the somatic findings of the AMDP-system. All 3 neuroleptics reduced the schizophrenic symptoms to a similar degree but showed differentiation as to their side effects.
Treatment-resistant schizophrenia: clinical experience with new antipsychotics.
Approximately 20-30% of patients with schizophrenia are resistant to conventional neuroleptics (i.e. are treatment-resistant). Clozapine has been shown to be effective in a proportion of treatment-resistant cases and to have a low side effect profile. However, it can cause agranulocytosis, is sedative and has marked anticholinergic properties. Risperidone, which is effective in chronic schizophrenia and has a low side effect profile and does not require routine blood monitoring, was compared with clozapine in a double-blind comparative study in 86 treatment-resistant patients. Preliminary findings indicate that, at endpoint, risperidone and clozapine were almost equieffective (total PANSS, PANSS subscales and CGI). Both drugs caused few adverse effects, and the severity of extrapyramidal symptoms was no different in the two groups. It is concluded that risperidone could be another drug effective in treatment-resistant schizophrenia. Further, larger trials will be needed to confirm this.
Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.
OBJECTIVE: The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.
METHOD: In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.
RESULTS: Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.
CONCLUSIONS: Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.
Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.
OBJECTIVE: Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.
METHOD: After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.
RESULTS: Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.
CONCLUSIONS: The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.
Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.
1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments.
Options:
A: Newer atypical antipsychotic drugs were found to be significantly more effective than clozapine in improving clinical outcomes.
B: Newer atypical antipsychotic drugs were found to be broadly similar to clozapine in terms of clinical effectiveness, but with different adverse effect profiles.
C: Clozapine was found to be significantly more effective than newer atypical antipsychotic drugs in improving clinical outcomes.
D: Newer atypical antipsychotic drugs were found to be less effective than clozapine and had a higher incidence of serious blood disorders.
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B
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74
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the main conclusion regarding the effectiveness of rifampicin-containing short-course chemotherapy regimens given two or three times a week compared to daily regimens in patients with pulmonary tuberculosis? Please answer this question based on the information provided below:
Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis.
Five 6-month antituberculosis regimens, allocated at random to patients with acid-fast bacilli in their sputum on microscopy, were studied. Four, given three times a week from the start, contained isoniazid and rifampicin together with (1) streptomycin, pyrazinamide, and ethambutol, (2) streptomycin and pyrazinamide, (3) streptomycin and ethambutol, or (4) pyrazinamide and ethambutol. The fifth was daily isoniazid, rifampicin, pyrazinamide, and ethambutol. All 833 patients with drug-sensitive strains of bacilli before treatment had a favourable bacteriological response during chemotherapy, and the bacteriological relapse rates during 12 months after stopping chemotherapy were 2% or less for all regimens except thrice-weekly isoniazid, rifampicin, streptomycin, and ethambutol (the only regimen without pyrazinamide), which had a relapse rate of 8%. The results were equally good for the 138 patients with bacilli resistant to isoniazid, streptomycin, or both drugs initially. The incidence of potentially serious toxicity was low. The daily regimen is relevant to programmes in which patients self-administer their drugs, and the 3 pyrazinamide-containing intermittent regimens are relevant to fully supervised outpatient programmes.
Options:
A: Intermittent regimens are significantly more effective than daily regimens.
B: Intermittent regimens are significantly less effective than daily regimens.
C: There is no significant difference in cure rates between intermittent and daily regimens, but more relapses were observed in the intermittent group.
D: Intermittent regimens are equally effective and have fewer relapses compared to daily regimens.
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C
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75
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the use of steroids in patients with cerebral malaria in terms of survival and long-term disability? Please answer this question based on the information provided below:
High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial.
We compared placebo and dexamethasone (initial dose, 3 mg/kg; total, 11.4 mg/kg per 48 h) in a double-blind trial involving 10 stuporous and 28 comatose patients with cerebral malaria. Patients were 18 mo to 42 y of age (geometric mean, 10.2 y), and the 19 patients in each group were comparable on admission. All patients received intravenous quinine therapy. Four patients (21%) in each group died. There were no significant differences between the placebo- and dexamethasone-treated groups in time until patients became afebrile (median, 51 vs. 19 h), the level of consciousness became normal (mean, 80 vs. 83 h), or parasitemia was cleared (mean, 2.1 vs. 3.4 d) or in the incidence of complications. Coma or hyperparasitemia (greater than or equal to 5% of erythrocytes parasitized) at the time of admission and hypoglycemia at any time during hospitalization were significantly correlated with a fatal outcome, which was not improved by using dexamethasone. We conclude that high-dose dexamethasone is not indicated for treating cerebral malaria.
Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients.
High-dose dexamethasone was compared with placebo in a double-blind trial involving 100 comatose patients with strictly defined cerebral malaria. The two treatment groups, whose members were six to 70 years old, proved comparable on admission. There were eight deaths in the dexamethasone group and nine in the placebo group (no significant difference; P = 0.8); at post-mortem examination the brain showed features diagnostic of cerebral malaria in all but one patient who died. Dexamethasone prolonged coma among the survivors: the interval between the start of treatment and the full recovery of consciousness was 63.2 +/- 5.9 hours (mean +/- S.E.M.) in the dexamethasone group, as compared with 47.4 +/- 3.2 hours in the placebo group (P = 0.02). Complications, including pneumonia and gastrointestinal bleeding, occurred in 26 patients given dexamethasone and 11 given placebo (P = 0.004). Only five patients had neurologic sequelae. Results were similar in a subgroup of 28 children six to 14 years old. Dexamethasone is deleterious in cerebral malaria and should no longer be used.
Options:
A: Steroids significantly improved survival rates and reduced long-term disability.
B: Steroids had no significant effect on survival rates and long-term disability.
C: Steroids significantly worsened survival rates and increased long-term disability.
D: Steroids significantly improved survival rates but had no effect on long-term disability.
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B
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76
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the conclusions regarding the effectiveness of vitamin E in treating intermittent claudication based on the review of controlled trials? Please answer this question based on the information provided below:
Treatment of intermittent claudication. A reappraisal of the value of alpha-tocopherol.
The treatment of intermittent claudication with vitamin E.
Treatment of intermittent claudication with vitamin E.
[D-alpha tocopherol in intermittent claudication. A clinical study].
Alpha-tocopherol in the treatment of intermittent claudication: a preliminary report.
Options:
A: Vitamin E was found to be highly effective in treating intermittent claudication, with significant improvements in all measured outcomes.
B: Vitamin E showed some positive effects on certain outcomes, but the evidence was insufficient to determine its overall effectiveness in treating intermittent claudication.
C: Vitamin E was found to have no effect on intermittent claudication, and no improvements were observed in any of the measured outcomes.
D: Vitamin E was associated with serious adverse effects, making it unsuitable for treating intermittent claudication.
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B
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77
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the effects of limited (information only) asthma education on health outcomes in adults with asthma? Please answer this question based on the information provided below:
International guidelines and educational experiences in an out-patient clinic for asthma.
In June 1989, an out-patient clinic for asthma was instituted at Crema Hospital, Italy. Up to November 1994, 430 adult asthmatics were recruited, classified and managed according to the recommendations of the international guidelines. The aims of this study are to verify: 1) whether the organization of the clinic could maintain asthma under control and reduce hospital admissions; and 2) whether the traditional educational approach could be implemented by lessons in the school of asthma to improve the control of asthma symptoms and/or admissions. The data reported refer to the first 360 asthmatics attending the clinic between 1989 and 1994: 53, 45 and 2% of them were suffering from extrinsic, intrinsic and occupational asthma, respectively. On recruitment, forced expiratory volume in one second (FEV1) was < 80% of predicted in 170 patients, and arterial oxygen tension (Pa,O2) 8.0 kPa (< 60 mmHg) in 27 patients. After the admission visit, 190 patients (53%) were classified as mild, 97 (27%) as moderate, and 73 (20%) as severe asthmatics. In May 1993, a school of asthma was organized. Forty four patients were recruited, stratified according to the severity of their asthma and randomized into two groups: 22 patients attended the school, and 22 patients did not. Each group consisted of 5, 10 and 7 patients with mild, moderate and severe asthma, respectively. The school comprised four lessons twice a week. One year after the end of the school, we could find no differences between the two groups (school versus controls) with regard to the number of urgent care visits (9 vs 9), scheduled visits (22 vs 21) and hospital admissions (2 vs 2).
The cost and effectiveness of an education program for adults who have asthma.
STUDY OBJECTIVE: To determine whether a self-management training program decreases emergency department visits and reduces costs for patients with asthma.
DESIGN: Randomized controlled trial of an educational program.
SETTING: Two sites--an urban emergency room and a suburban emergency room.
PATIENTS: 241 asthma patients between the ages of 18 and 70 years. Of the 119 patients in the intervention group and the 122 in the control group, 185 (76%) were available for follow-up.
INTERVENTION: All patients seen in the emergency departments were given usual medical care and follow-up. Patients in the intervention group were asked to attend three educational sessions on asthma conducted by a specially trained RN. The program stressed importance of medication compliance, methods to control and prevent attacks, effects of drugs and rationale for their use, relaxation exercises, and smoking cessation.
MEASUREMENT AND MAIN RESULTS: All patients received telephone interviews four, eight, and 12 months after entry into the study. Reports based on hospital admissions and emergency room utilization were verified by billing records. Three patients died during the study, none from asthma-related problems. The intervention group had significantly fewer asthma-related emergency visits (16 visits per 100 persons) than did the control group (39 per 100 persons); p = 0.0005 for the 12 months of follow-up. The effect of the intervention on asthma-related emergency department visits was strongest during the initial four months postintervention (68 per 100 persons versus 220 per 100 persons, p = 0.003). The financial analysis showed that the $85/person cost for the educational sessions was offset by the $628/person reduction in emergency room charges.
CONCLUSION: Education enables patients with asthma to decrease utilization of emergency services.
Health outcomes among African American and Caucasian adults following a randomized trial of an asthma education program.
OBJECTIVES: Re-analysis of a randomized trial of an asthma education program designed to assess the effects of the intervention on emergency department visits, limited days of activity and asthma knowledge and beliefs separately for African American and Caucasian adults with asthma.
DESIGN: Two hundred and forty-one respondents between the ages of 18 and 70 were evaluated in two emergency departments (one inner city and one suburban location) of a large, midwestern health care system and were randomized to an intervention or control group.
RESULTS: Regardless of race, members of the intervention group showed a decrease in the number of post-intervention emergency department visits (ANOVA interaction between race and group effect p value = 0.93). The greatest decrease occurred during the first four post-intervention months. No differential effect of the asthma education intervention by race was found on the change in asthma knowledge and beliefs over the study period (ANCOVA interaction between race and group effect p value = 0.60).
CONCLUSION: This study demonstrates that post-intervention, both African American and Caucasian study participants showed a decrease in emergency department visits and an increase in asthma self-management. This finding is especially important for African Americans, who face increasing asthma mortality and morbidity.
Controlled evaluation of the effects of patient education on asthma morbidity in general practice.
Two different patient education programmes for asthma in general practice were evaluated in a controlled trial. Knowledge, self management, and morbidity due to asthma were assessed in 339 patients by means of a questionnaire. One group then received a maximum education programme, a second group received a limited education programme, and a third acted as a control group. 274 patients were reassessed after one 1 year. In both the intervention groups, understanding of asthma was greater after the trial. Only in the maximum intervention group was a significant improvement in knowledge of asthma shown. Neither group showed any change in self-management ability or asthma morbidity that differed significantly from changes in the control group. These simple informational education programmes were ineffective when applied to a general practice population. Further studies of factors affecting attitudes, beliefs, and actions are needed to improve the advice and support given to asthma patients.
Computer education for asthmatics: what effects?
Comparison of effects of a self management booklet and audiocassette for patients with asthma.
The effects on self management of asthma of a specially prepared book and audiocassette tape with similar contents were observed in a controlled study of 177 patients with asthma in general practice. After a run in period of six months patients were randomly given the book, the tape, both the book and tape, or neither. Patients' knowledge of the use of drugs, perceptions of their disability, skill in using an inhaler, consumption of drugs, consultations with their general practitioners, morbidity (from patients' entries on diary cards), and use of the educational material were measured. Knowledge about the use of drugs was significantly increased in the groups who received the material after three months and persisted after 12 months. Patients who had been given the tape or the book and tape increased their scores of knowledge of drugs more than patients given the book alone. Patients in all groups given the material considered that their disability was reduced. There were no other significant changes. Patients given both the book and the tape preferred the book. Patients with asthma can obtain useful information from such material. The paradoxical result whereby patients learnt more from the tape but preferred the book suggests that a distinction can be made between information that patients need, which may be acquired better from an audiocassette, and information that they want, which may be acquired better from a book.
Education for self-treatment by adult asthmatics.
A prospective experimental design evaluated the ability of a series of educational and motivational interventions to enhance self-treatment by adult asthmatics and to reduce use of emergency department services for asthma attacks. After treatment for an asthma attack, subjects were randomly assigned to the following sequential interventions: (1) reinforcement by interpersonal similarity at the time of the emergency visit, (2) recepit of positive written appeals, and (3) follow-up telephone reinforcement. The asthmatic nurse educator was generally more effective in achieving short-term reduction of emergency department visits. Although the usefulness of the positive written appeal increased when employed by the asthmatic nurse, there were no substantive independent effects of the written message on emergency department use.
Videotape educational program for people with asthma.
A videotape educational program was produced for use in adults with asthma. The program provided an overview of lung function, the physiologic abnormalities and treatment of asthma, and the approach to common problems encountered by the patients. Its benefits were examined in a randomized controlled study. The efficacy of the program in 62 patients whose mean duration of illness was 17 years was assessed by comparing the level of knowledge of the experimental group immediately after viewing the tape with that of the controls, who had not seen it; the experimental group scored significantly higher than the control group. Retention of knowledge attributed to the program was assessed after a mean interval of 16 months. The knowledge test score of the experimental group was found to have decreased to the level of the control group. The main areas in which the experimental group lost knowledge were self-care and drug therapy for asthma. The medical status of the two groups did not change appreciably over the period of the study.
Reducing hospital admission through computer supported education for asthma patients. Grampian Asthma Study of Integrated Care (GRASSIC).
OBJECTIVE: To evaluate a personalised computer supported education programme for asthma patients.
DESIGN: Pragmatic randomised trial comparing outcomes over 12 months between patients taking part in an enhanced education programme (four personalised booklets, sent by post) and patients receiving conventional oral education at outpatient or surgery visits.
SETTING: Hospital outpatient clinics and general practices in north east Scotland.
SUBJECTS: 801 adults attending hospital outpatient clinics, with a diagnosis of asthma confirmed by a chest physician and pulmonary function reversibility of at least 20%.
MAIN OUTCOME MEASURES: Numbers of hospital admissions, consultations with general practitioner for asthma, steroid courses used, bronchodilators and inhaled steroids prescribed, days of restricted activity, and disturbed nights.
RESULTS: Patients with asthma judged too severe for randomisation between clinic care and integrated care and thus retained in clinic care had 54% fewer hospital admissions after receiving enhanced education than did the control group (95% confidence interval 30% to 97%; P < 0.05) over the study year. Patients had not all spent a full year as "educated" patients within the study year: when "educated days" were controlled for, annual admission rates for the entire enhanced education group were 49% (31% to 78%) of those in the control group. Among patients with sleep variation, sleep disturbance in the education group in the week before a regular review was 80% (65% to 97%) of that in the control group. There was no significant difference in days of restricted activity, prescription of bronchodilators or inhaled steroids, use of oral steroids, or number of general practitioner consultations for asthma, and no significant interaction between ownership of a peak flow meter and education.
CONCLUSIONS: An asthma education programme based on computerised booklets can reduce hospital admissions and improve morbidity among hospital outpatients.
Education of adult patients at an "asthma school": effects on quality of life, knowledge and need for nursing.
The effect of education of adult asthma patients at a special "asthma school" was studied with regard to knowledge of the disease and its treatment and quality of life measured by leisure activities, social interaction and psychological well being. We also studied if there were any differences in number of days in hospital and emergency visits before and one year after the asthma-school. Patients were randomised to an intervention group (7 men and 13 women) and a control group (7 men and 11 women). The age-range was 22-66 yrs. Both groups answered the same standardized and quantified questionnaires on three occasions, before the start of the asthma school, after five months and after twelve months. Both groups increased their knowledge of the disease and how to treat it, with slightly better results in the intervention group. The self-assessments all showed that patients in the intervention group felt better than those in the control group. The number of days in hospital as well as acute visits to out patients clinics were reduced significantly after the asthma school. The intervention did not influence spirometric variables.
The economics of an intensive education programme for asthmatic patients: a prospective controlled trial.
The costs and benefits of a planned patient education programme for patients with asthma were evaluated in a controlled trial. The patient education group received a planned patient education programme, performed by a physician, a pharmacist and a nurse over a 6-month period. Changes in the use of resources, productive output and in health status were measured for the patient education group and the control group. The total cost for planning, implementation and evaluation of the programme was 14074 British pounds sterling. The patient education group increased its contacts to general practitioners and the extra costs totalled 252 British pounds sterling. The increased costs of drugs used by the patient education group in the 6-month period was 2313 British pounds sterling compared with costs in the control group. The number of days lost through sickness decreased in the patient education group, corresponding to a 4528 British pounds sterling saving of otherwise lost earnings. The quality of life increased in the patient education group by 3.2 points on the Psychosomatic Discomfort Scale (2.9%). Health status increased by 38.9%. The study shows that the patient education programme has a positive clinical effect on the patient's quality of life and health status. The economic consequences of the implementation programme depend on the specific setup of the local healthcare system, where the programme is applied.
Educating asthmatic patients in primary care: a pilot study of small group education.
Patient education is an important part of asthma management. Individual education is usually used for this task. The object of this study was to assess whether another educational technique, educating patients in small groups, would be as effective and as acceptable as individual counselling in improving knowledge about asthma. A specially designed questionnaire was used to assess knowledge and other variables before and after education. Thirty-four patients were educated individually and 34 patients were educated in small groups. There were significant improvements in knowledge scores after both types of education. However group education took 4.5 hours for 34 patients whereas individual counselling took 14.25 hours for the same number. The results of this study suggest that educating patients in small groups is as effective as individual counselling in improving knowledge of asthma, is acceptable to patients and takes much less time.
Patients' perceptions compared with objective ratings of asthma severity.
BACKGROUND: Optimal asthma management requires accurate assessment of asthma severity.
OBJECTIVE: To compare patients' perceptions of their asthma severity with that obtained by using the guidelines published by the National Asthma Education and Prevention Program's Expert Panel and with functional impairment measured by spirometry and numeric criteria of the American Thoracic Society.
METHODS: We enrolled 323 patients age 18 to 50 years who were members of the Kaiser Foundation Health Plan for > or = 1 year in a randomized control trial of an asthma education program. Each had a confirmed diagnosis of bronchial asthma and had been receiving antiasthma medication for > or = 1 year. Patients rated the severity of their asthma. Office spirometry was performed, and, using the Mini-Wright peak flow meter, patients kept 2-week diaries of at-home recordings of morning and evening peak expiratory flow rates.
RESULTS: A statistically significant association was noted between patients' perceptions of asthma severity and both medication severity rating (P < .001) and diurnal variation rating (P = .003) and evening peak expiratory flow rate percentage (P = .019). In comparison with a severity composite based on criteria of the National Asthma Education Program, 54% of patients accurately estimated asthma severity, 27% overestimated, and 20% underestimated severity.
CONCLUSION: A clinically significant proportion of asthmatic patients substantially underestimate disease severity and thereby may be at risk of increased mortality or morbidity.
A controlled trial of two forms of self-management education for adults with asthma.
PURPOSE: Excess morbidity and mortality due to asthma, aggravated by demonstrably poor patient self-management practices, suggest the need for formal patient education programs. Individual and group asthma education programs were developed and evaluated to determine their cognitive, behavioral, and clinical effects.
PATIENTS AND METHODS: We compared changes in asthma symptoms, utilization of medical services, knowledge about asthma, metered-dose inhaler (MDI) technique, and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were randomly assigned to small-group education, individual teaching, or 1 of 2 control conditions--an information (workbook) control or usual control (no formal asthma education). Data were collected from patients by questionnaire, diary, and physical examination at enrollment and at 5 months and 1 year after intervention. Medical record data on these patients were abstracted for a total 3-year period, from 1 year before to 2 years after enrollment.
RESULTS: Compared with the usual control, the self-management education programs were associated with significant improvements in control of asthma symptoms (reduced "bother" due to asthma and increased symptom-free days), MDI technique, and environmental control practices. Small-group education also was associated with significant improvements in physician evaluation of the patients' asthma status and in patients' level of physical activity. For both group and individual education recipients, improvement in MDI technique was positively correlated with improved control of symptoms; however, the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone. The time course over which changes occurred in the various outcome measures suggests the mechanism by which education resulted in improvement in the patient's status. Significant improvements in MDI technique and environmental control practices were manifest immediately following education (5-month follow-up) and at the 1-year follow-up. Significant improvements in symptom measures were not apparent until the 1-year follow-up. The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period, but this decrease did not differ significantly among treatment conditions. However, there was a trend toward greater reduction in patients receiving small-group education. An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed. This result must be regarded as tentative, since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues. However, this trend is consistent with the antecedent benefits of the small-group education, and appears to warrant further investigation.
CONCLUSIONS: Carefully designed asthma education programs for adults can improve patients' understanding of their condition and its treatment and increase their motivation and confidence that the condition can be controlled, thereby increasing their adherence to the treatment regimen and management of symptoms, and, in turn, improving control of symptoms. Both small-group education and individual education were associated with significant benefits, but the group program was simpler to administer, better received by patients and educators, and more cost-effective. The results show promise for improving clinical outcomes, through well-designed educational programs, for patients with asthma and other chronic health problems.
An evaluation of approaches to asthma self-management education for adults: the AIR/Kaiser-Permanente Study.
The purpose of the AIR/Kaiser-Permanente asthma project is to evaluate various approaches to the education of adults with asthma, identifying those types of patients for whom particular approaches are most cost effective. Critical self-management practices for adults with asthma were identified using the critical incident technique. An individualized and a group administered educational program are being developed to teach the identified critical skills, using the instructional models previously employed in AIR WISE and AIR POWER programs for children with asthma. Three hundred patients with moderate to severe asthma from Northern California Kaiser-Permanente Medical Group clinics will participate in a trial of these programs. Patients will be randomly assigned to one of four conditions: One of two educational programs, an information/attention control, or a data-only control condition. Data will be collected on all patients for 15 months; health care utilization data covering a two-year period will be available from medical records. Program effectiveness will be evaluated in terms of pre-post changes in the patients' knowledge, attitudes, self-management practices, medical condition, daily functioning, and utilization of services. Cost effectiveness will be evaluated, paying specific attention to the cost effectiveness of different educational approaches for different types of patients.
Options:
A: It significantly reduced hospitalisations and doctor visits.
B: It had no effect on hospitalisations, doctor visits, lung function, and medication use, but improved perceived asthma symptoms.
C: It significantly improved lung function and reduced medication use.
D: It reduced days lost from normal activity and emergency department visits.
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B
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78
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the objective of the review on the effectiveness of mecamylamine in smoking cessation? Please answer this question based on the information provided below:
Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone.
OBJECTIVE: To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.
METHODS: This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms.
RESULTS: The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite.
CONCLUSIONS: Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.
Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy.
The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.
Options:
A: To determine the effectiveness of mecamylamine in promoting smoking cessation, either alone or in combination with nicotine replacement therapy.
B: To compare the side effects of mecamylamine and nicotine replacement therapy in smoking cessation.
C: To evaluate the long-term health benefits of smoking cessation using mecamylamine.
D: To analyze the cost-effectiveness of mecamylamine in smoking cessation programs.
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A
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79
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effectiveness of episodic high dose inhaled corticosteroids compared to maintenance low dose inhaled corticosteroids in the treatment of mild episodic viral wheeze in children? Please answer this question based on the information provided below:
Prevention of viral induced asthma attacks using inhaled budesonide.
Thirty two preschool children were entered into a double blind, placebo controlled study using intermittent budesonide to treat viral induced wheeze. Active treatment was either 800 micrograms twice a day via a spacer or 1600 micrograms twice a day via a spacer and facemask in those children too young to use a mouthpiece. Treatment was started at the onset of an upper respiratory tract infection and continued for seven days or until symptoms had resolved for 24 hours. Each child remained in the study until they had completed using one pair of budesonide and placebo inhalers in random order without the need for additional oral prednisolone. Twenty five children completed 28 treatment pairs. All 25 families were asked to express a preference after completing their first treatment pair: 12 preferred budesonide and six preferred placebo; seven had no preference. Symptom scores were compared in 17 treatment pairs that were completed without the need for oral prednisolone. Mean day and night time wheeze in the first week after infection were significantly lower in those receiving budesonide. Intermittent inhalation of budesonide can modify the severity of wheezing in preschool children developing asthma after viral respiratory infections but improvements were modest with the doses used in this study.
Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial.
OBJECTIVES: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children.
DESIGN: Randomised, double blind, placebo controlled trial.
SETTING: Community based study in Southampton.
SUBJECTS: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months.
INTERVENTIONS: After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly.
MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate.
RESULTS: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 1; adjusted difference 0.09 1 (95% confidence interval 0.04 to 0.14); P = 0.001) and methacholine PD20 12.8 v 7.2 mumol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P = 0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups.
CONCLUSIONS: Although lung function is improved with regular beclomethasone dipropionate 400 micrograms/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection.
Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers.
The aim of this study was to investigate whether budesonide, for 10 d, administered at the first sign of an upper respiratory tract infection, could reduce asthma symptoms in 1-3-y-old children with asthma during infections. The primary efficacy variable was symptom scores. The study had a multicentre, randomized, double-blind, placebo-controlled design with parallel groups. Fifty-five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask. Each child was monitored for 1 y. Budesonide was given 400 microg q.i.d. for the first 3 d and b.i.d. for 7 d. Symptoms (cough, wheeze, noisy breathing and breathlessness) were scored (0-3) daily by the parents. Asthma symptom scores were lower in children treated with budesonide than in those given placebo. The effect was most pronounced for cough and noisy breathing, but it did not affect the need for hospital care. In conclusion, treatment with budesonide, started at the first sign of a respiratory infection, reduced asthma symptoms in toddlers with episodic asthma.
Treatment of acute, episodic asthma in preschool children using intermittent high dose inhaled steroids at home.
In a double blind, controlled trial, the effect of high dose beclomethasone dipropionate (750 micrograms three times daily for five days) administered by metered dose inhaler and valved spacer, was compared with placebo, during 70 paired episodes of acute asthma in 24 preschool children. Treatment commenced at home at the first sign of an attack. Parents' blind preference for active treatment was significant. Data from 17 pairs of treatment, however, were affected by interventions such as hospital admission or oral corticosteroid treatment. These events occurred similarly in active and control periods. An intrasubject comparison was made of diary scores from the 18 pairs of episodes in which no intervention occurred in either the active or placebo treatment. Both daytime and night symptoms over the first week of the attack were significantly reduced by active treatment. Intermittent high dose inhaled beclomethasone dipropionate is beneficial in modifying the severity of acute episodic asthma in preschool children able to use a spacer device.
Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children.
Acute episodic wheeze related to viral infections is a common and distressing condition and treatment remains unsatisfactory. Although some benefit from the continuous use of inhaled steroids has been demonstrated in young wheezy children, their effect primarily on acute episodes has not been considered. In this study the effect of budesonide (400 micrograms/day) was assessed in a four month double blind parallel trial, in 41 children (0.7-6.0 years) with predominantly episodic viral wheeze. Analysis of the last three months showed no difference between budesonide or placebo in mean daily total symptom score (median values 0.6 and 0.63), episode number (mean values 2.6 and 2.4), or score/episode (mean value 30 and 31). Four months of treatment with inhaled budesonide had no effect on acute episodes of wheeze in this group of children.
Options:
A: Episodic high dose inhaled corticosteroids are more effective in reducing the requirement for oral corticosteroids and are preferred by parents.
B: Maintenance low dose inhaled corticosteroids are more effective in reducing the requirement for oral corticosteroids and hospital admissions.
C: Both episodic high dose and maintenance low dose inhaled corticosteroids are equally effective in reducing the requirement for oral corticosteroids.
D: Neither episodic high dose nor maintenance low dose inhaled corticosteroids are effective in reducing the requirement for oral corticosteroids.
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A
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80
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness and adverse effects of zuclopenthixol decanoate compared to other depot antipsychotic preparations in the treatment of schizophrenia and similar serious mental illnesses? Please answer this question based on the information provided below:
Clopenthixol decanoate and perphenazine enanthate in schizophrenic patients. A double-blind Nordic multicentre trial.
The clinical properties of clopenthixol decanoate has been investigated versus perphenazine enanthate in a double-blind clinical multicentre trial including 14 psychiatric hospitals in Finland, Sweden, Norway, and Denmark. Test treatment was initiated in 172 chronic schizophrenic patients and the planned 6 months test period was completed by 57 patients receiving clopenthixol decanoate and 48 receiving perphenazine enanthate. The therapeutic effect was assessed by means of CGI, BPRS, and NOSIE-30 and was found significant with both test drugs. Significant differences in the effect were seen only in "Hostile-suspiciousness" (BPRS) and "Social interest" (NOSIE-30). For these items clopenthixol decanoate was found superior to perphenazine enanthate. The influence of side effects on the patients' functioning was found to be slightly, but not significantly more troublesome in the perphenazine enanthate patients.
Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.
Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug.
Aspects of clinical psychiatric research on depot neuroleptics. The presentation of two double-blind trials with cis(z)-clopenthixol decanoate and a withdrawal study in schizophrenics.
Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. II. Factor analysis of the CPRS sub-scale for schizophrenia.
Eleven factors were obtained by factor analysing the CPRS results from a longitudinal treatment process study in chronic schizophrenics during maintenance phase. Such factors may give more reliable information than the single item. Two factors--"anxiety-depression-asthenia" and "psychotic" (psychotic schizophrenic symptoms and signs)--nonpsychotic rating of anxiety and depressive symptoms as well as definite psychotic-schizophrenic symptoms, respectively--demonstrated special value for the clinical work, i.e. being relevant instrument for monitoring a treatment process.
Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. IV. Serum levels and clinical outcome.
Two pharmacolkinetic parameters viz. the minimum serum concentration in the dosage interval and the sera under the serum concentration curve have been correlated to 14 parameters for clinical outcome, viz. total points and factor points from the three rating scales, BPRS, CPRS, and side effects scale, in a double blind clinical trial of clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. No statistically significant correlations were observed. It is of some interest, however, that the results suggest that the treatment of individual patients with neurleptics may be adjusted by means of repeated ratings, residual percentage, changes in psychopathology, and determinations of serum concentrations. Our results do not indicate any optimal concentration range for these depot neuroleptics in the maintenance phase of schizophrenia. The so-called therapeutic window as to neuroleptics obviously varies with regard to the phase of the disease as well as the patients' social situation.
The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.
Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed.
The positive and negative symptoms of schizophrenia: patterns of response to depot neuroleptic treatment.
The pattern of response of positive and negative symptoms of schizophrenia to depot neuroleptics was studied in a Nigerian Sample of schizophrenics in a drug-free state. Both positive and negative symptoms showed significantly good response, but positive symptoms were more responsive. Cultural factors do not seem to influence the pattern of response. Rather, neuroleptic naivety may enhance the responsivity of positive symptoms, whereas stimulating millieu (non-pharmacologic) factors may enhance that of negative symptoms.
Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.
Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.
Options:
A: Zuclopenthixol decanoate was less effective in preventing relapses and had fewer adverse effects compared to other depot preparations.
B: Zuclopenthixol decanoate was more effective in preventing relapses but had more adverse effects compared to other depot preparations.
C: Zuclopenthixol decanoate was equally effective in preventing relapses and had the same level of adverse effects as other depot preparations.
D: Zuclopenthixol decanoate was less effective in preventing relapses and had more adverse effects compared to other depot preparations.
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B
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81
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effectiveness of Mycobacterium vaccae immunotherapy in treating tuberculosis? Please answer this question based on the information provided below:
Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 1. Newly-diagnosed pulmonary disease.
In this study, 206 previously untreated patients with sputum culture positive pulmonary tuberculosis were randomized to receive an injection of killed Mycobacterium vaccae as immunotherapy, or of saline as placebo, after 1 month of a 6-month chemotherapeutic regime. Not surprisingly in a disease for which there is good chemotherapy, the difference in numbers which were culture negative at the end of treatment was small, and the final outcome at the latest post-treatment follow-up did not reach statistical significance between the two arms of the study. Nonetheless, those receiving immunotherapy showed better progression in every parameter measured, suggesting faster and more complete cure. Whereas seven of 97 patients receiving immunotherapy required a course of re-treatment and five still had active disease after a mean follow-up of 2 yr, 13 of 109 placebo recipients required re-treatment and nine still had active disease at the end of the study. Only one patient receiving M. vaccae plus chemotherapy died of tuberculosis, compared with four of those receiving chemotherapy alone. A degree of drug resistance was shown by the bacilli cultured from 25 of 175 (14%) patients, and seven of them (4.0%) were multi-drug resistant. Fourteen patients received immunotherapy of whom 13 were cured, including all three of those showing multi-drug resistance. Of the 11 patients with drug resistance in the control group, eight were cured, and one patient with multi-drug-resistant disease died of tuberculosis during re-treatment.
Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 2. Chronic or relapsed disease.
In this study of 102 patients with culture-positive chronic treatment failure or repeatedly relapsed pulmonary tuberculosis receiving chemotherapy, 56 received an injection of killed Mycobacterium vaccae as immunotherapy after 1 month of treatment. At the start of treatment, there was little difference between those receiving immunotherapy and the 46 patients in the control group receiving chemotherapy alone. Thereafter, the two groups diverged so that 1 yr later, 43 of 56 (77%) patients receiving M. vaccae had a successful outcome, in comparison with 24 of 46 (52%) patients receiving chemotherapy alone (P < 0.02). Successful results were obtained from patients infected with drug-resistant bacilli, 20 of 32 (63%) patients compared with 11 of 25 (44%) patients, respectively, as well as from fully drug-sensitive cases (23 of 24 compared with 12 of 21 patients; P = 0.004). At the final follow-up after 22 months, 13 of 56 patients receiving immunotherapy had an unfavourable outcome compared with 26 of 46 members of the control group (P = 0.0006). During the study, 16 patients died of tuberculosis (six after immunotherapy), and 12 were lost to follow-up. Not only was bacteriological success improved by immunotherapy, chest X-ray showed markedly better resolution of cavities and other radiological lesions, recovery of body weight was improved, and the mean erythrocyte sedimentation rate returned almost to normal (P < 0.001) in comparison with those receiving chemotherapy alone. These changes were seen even in those failing bacteriological cure, suggesting that the immunotherapy had been effective, but that bacilli were replicating in an extracellular situation, protecting them from its effects.
Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Durban Immunotherapy Trial Group.
BACKGROUND: Mycobacterium vaccae, an environmental saprophyte, has immunogenic properties that enhance the host immune response. Immunotherapy with M. vaccae has been suggested to shorten short-course antituberculosis chemotherapy. We tested the hypothesis that the addition of M. vaccae to standard short-course antituberculosis chemotherapy would decrease the time to achieve a negative sputum culture.
METHODS: Patients with newly diagnosed tuberculosis were randomly assigned an injection of saline (placebo) or M. vaccae on day 8. All patients received antituberculosis chemotherapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. Sputum samples were checked by microscopy and culture every week for the first 8 weeks and monthly until the end of chemotherapy at 6 months. The primary outcome was the time to a negative sputum culture in the first 8 weeks. Intention-to-treat analysis was used and time to sputum clearance was assessed by log-rank test and Cox's proportional-hazards regression.
FINDINGS: 172 patients received M. vaccae and 175 patients received placebo. At 8 weeks, 70 patients in the M. vaccae group and 65 patients in the placebo group had a negative culture; there was no difference between groups in the time to a negative culture (p=0.83). There was no interaction between HIV status and treatment.
INTERPRETATION: M. vaccae immunotherapy has no benefit when added to standard antituberculosis chemotherapy.
Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration.
Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.
Mycobacterium vaccae: a study of safety and outcome measures.
Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial.
BACKGROUND: Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients.
METHODS: The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result.
FINDINGS: Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172.
INTERPRETATION: Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated.
An investigation of patients with pulmonary tuberculosis in Kuwait in preparation for studies of immunotherapy with Mycobacterium vaccae.
Sixty-five patients, many of them immigrant to Kuwait, with bacteriologically proven, adult type, pulmonary tuberculosis were studied by many parameters over the 4 months following diagnosis. Twelve were infected with tubercle bacilli resistant to at least one anti-tuberculosis drug. Preliminary evidence suggested that this was frequently primary resistance in patients infected in their countries of origin. The Kuwaiti environment results in very high skin test and lymphocyte proliferative responses (LTT) to shared and species specific antigens of mycobacteria in healthy persons. In comparison, patients with tuberculosis lacked cellular responses to group i and group ii antigens, but had increased IgG and IgA binding to mycobacterial antigens in general. LTT responses to added interleukin 2, and production of alpha interferon, were normal in our patients, but induction of gamma interferon in response to phytohaemagglutinin was reduced initially, rising towards normal during treatment. Biochemical and haematological abnormalities present at the time of diagnosis rapidly corrected. The disease differed from that reported in most previous studies in that fever was uncommon, the disease was never fatal, and most tuberculin tests were not necrotising. This implied that a detrimental immunopathological component is less pronounced in those exposed to the Kuwaiti environment, and a hypothesis is put forward to explain this.
Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis.
47 patients with adult-type pulmonary tuberculosis attending the Chest Diseases Hospital in Kuwait were given a single injection of 10(9) irradiation-killed M. vaccae after 1 month of a 9-month course of chemotherapy. The patients were followed-up for 3 more months in double blind comparison with 65 patients given an injection of saline (placebo). The immunotherapeutic injection produced a small local lesion in 44/47 patients, 18 of which ulcerated and produced small scars. Immunotherapy made no measurable difference to the bacteriological, biochemical, haematological, or radiological parameters measured. However it was associated with significantly improved weight gain, reduced size of skin test response to Tuberculin, increased lymphocyte proliferation to common mycobacterial antigens, and increased antibody levels to mycobacterial antigens. The changes in skin test and LTT responses were related and occurred in 29% of patients whose recognition of common mycobacterial antigens returned to normal. The remaining patients did not differ in these respects from those receiving placebo. The proportion of patients whose responses were improved was very similar to that achieved using the same immunotherapeutic agent in a group of treated multibacillary leprosy patients.
[A clinical study on vaccine of Mycobacterium vaccae in treating pulmonary tuberculosis].
OBJECTIVE: To study the effect of vaccine of Mycobacterium vaccae on cell-mediated immunity and on treating patients with pulmonary tuberculosis.
METHODS: Seventy cases of pulmonary tuberculosis with smear positive and initial treatment were classified randomly into group I (35 cases) and group II (35 cases), receiving 2HRZS/4HR and 2HRZS/4HR plus vaccine of Mycobacterium vaccae regimens respectively. Thirty-one multi-drug resistant pulmonary tuberculosis cases were classified into group III, receiving 4 - 6 sensitive antituberculous drugs and vaccine of Mycobacterium vaccae. Improvement of clinical symptoms, resolution of pulmonary lesions, negative conversion of sputum and changes of immunological functions were observed.
RESULTS: No significant difference in improvement of symptoms was found in group I and group II (P > 0.05), and the improvement rate of clinical symptoms in group III was found more than 50%. X-ray resolution rates in 4th month were 83% and 89%, and cavity reducing rates 40% and 50% respectively in group I and group II, and no significant differences were found (P > 0.05). X-ray resolution rate was 29%, cavity reducing rate 7% and no deteriorated case was found in group III. Sputum negative conversion rates in 1st, 2nd, 3rd and 4th month were 23%, 51%, 83% and 97% respectively in group I, while 31%, 77%, 89% and 100% in group II, and 3%, 16%, 29% and 32% in group III. Significant difference was found between group I and group II in sputum negative conversion rate in 2nd month after treatment (P < 0.05). After treatment, values of lymphocyte transformation test (LTT), CD(3), CD(4) and CD(4)/CD(8) of the above 3 groups were all higher than that before the treatment (P < 0.05), level of tumor necrosis factor decreased in group II and IL-2, IL-6 increased in group III.
CONCLUSIONS: Vaccine of Mycobacterium vaccae is a good immunotherapy preparation, which promotes sputum negative conversion and activation of cell-mediated immunity.
Options:
A: It significantly reduced mortality and improved sputum culture results.
B: It had no effect on mortality and showed no consistent effect on sputum negativity or sputum culture, with a high level of adverse reactions.
C: It significantly improved patient outcomes with minimal adverse reactions.
D: It showed a consistent positive effect on sputum negativity and reduced adverse reactions.
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B
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82
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effect of a single dose of nedocromil sodium on exercise-induced bronchoconstriction? Please answer this question based on the information provided below:
Nedocromil sodium in exercise-induced bronchoconstriction in children.
Twenty asthmatic children were studied in a double-blind within-patient comparative trial designed to assess the efficacy of nedocromil sodium (4 mg) and placebo in exercise-induced bronchoconstriction. The response to exercise challenge given 30 minutes after treatment showed statistically significant differences in favor of nedocromil sodium. No unusual symptoms were reported.
A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise-induced bronchoconstriction.
Fourteen adult subjects with stable asthma were treated using a double-blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24-53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise-induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient.
Nedocromil sodium and exercise induced asthma.
Serial exercise tests were carried out by 12 children with asthma on two study days. After a control exercise test either nedocromil sodium 4 mg or placebo were given double blind by metered dose inhaler. Highly significant inhibition of exercise induced asthma occurred after nedocromil, lasting for over two hours.
Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children.
To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG) administered by metered dose inhaler (MDI) in preventing exercise-induced asthma (EIA), 12 asthmatic children with EIA were studied in a randomized, double-blind, cross-over, placebo-controlled study. NS and SCG were given by MDI alone, and by MDI with a 700 ml spacer device (Fisonair, Fisons, UK), in order to assess the benefit of using such a device. Following a baseline exercise challenge, the protective effect of NS, SCG or placebo was evaluated in each subject. The percentage fall in forced expiratory volume in one second, and percentage protection were measured. NS and SCG provided a significant and comparable protection from EIA, and both were better than placebo. No further improvement was observed after drug administration via the spacer. Both NS and SCG are effective in preventing EIA in children, when administered at the recommended clinical dose, and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good.
Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children.
Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.
The Effect of Cromolyn Sodium and Nedocromil Sodium Administered by A pressurized Aerosol with A spacer Device on Exercise-Induced Asthma in Children.
To compare the effectiveness of cromolyn sodium (CS) (10 mg) and nedocromil sodium (NS) (4 mg) administered by a metered dose inhaler (MDI) with a spacer device in preventing exercise-induced asthma (EIA), eight asthmatic children with EIA were studied in a randomized double-blind, cross-over, placebo-controlled study, CS and NS provided significant, comparable protection from EIA and both were better than placebo. We conclude that CS and NS administered by a pressurized aerosol with a spacer device provide equal protection against EIA in children.
Cromolyn versus nedocromil: duration of action in exercise-induced asthma in children.
Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by a metered dose inhaler, were compared in their efficacy and duration of action in preventing exercise-induced asthma in children. After a screening test was performed, 13 patients with asthma performed standard exercise tests 20 minutes and 140 minutes after drug inhalation in a randomized, double-blind, crossover study. Both drugs were significantly more protective than placebo after 20 minutes, but no significant difference was seen between cromolyn sodium and nedocromil sodium. No difference between active drugs and placebo was found 140 minutes after inhalation. At these clinically recommended doses both cromolyn sodium and nedocromil sodium provide equal protection against exercise-induced asthma, and the duration of action of both lasts for less than 2 hours.
Effect of nedocromil sodium on exercise-induced bronchoconstriction in children.
A double-blind, placebo-controlled, crossover study investigated the efficacy of nedocromil sodium in reducing bronchoconstriction subsequent to exercise challenge in asthmatic children. Twelve children aged 7-14 years (mean 10.8 years) were pretreated with nedocromil sodium aerosol (2 inhalations; 2 mg/inhalation) or matching placebo, 30 min prior to treadmill running. Lung function was measured at regular intervals postexercise and the mean maximum percentage decrease in PEF and FEV1 compared following nedocromil sodium or placebo pretreatment. Nedocromil sodium significantly reduced the fall in PEF (P less than 0.001) and FEV1 (P less than 0.001) and provided significantly greater protection (P less than 0.001) than placebo. No adverse reactions or unusual symptoms were observed.
The preventive effect and duration of action of nedocromil sodium and cromolyn sodium on exercise-induced asthma (EIA) in adults.
Nedocromil sodium, 4 mg, from a metered-dose inhaler, cromolyn sodium, (cr) 20 mg, from a Spinhaler, and placebo (pl) were compared in their efficacy and duration of action in preventing exercise-induced asthma. Twelve patients with asthma performed treadmill exercise tests 20 minutes, 2 hours, and 4 hours after a single dose of drug in a double-blind, crossover trial. Both active drugs were significantly better than pl at 20 minutes. Two hours after drug administration, only cr was significantly different from pl. The direct comparison between nedocromil and cr demonstrated no significant difference on FEV1, and the only significant difference was with forced expiratory flow between 25% and 75% of vital capacity at 2 hours. It is concluded that at these clinically recommended doses, both drugs are equally effective in preventing exercise-induced asthma with cr possibly having a somewhat longer duration of action.
Effects of nedocromil sodium, cromolyn sodium, and a placebo in exercise-induced asthma.
The incidence and severity of exercise-induced asthma were determined in nineteen asthmatic patients who performed eight minutes of exercise following four treatments administered in a random order. The treatments were nedocromil sodium, cromolyn sodium, placebo, and no treatment. It was concluded that nedocromil sodium (8 mg) and cromolyn sodium (4 mg) provide equal protection against exercise-induced asthma.
The preventive effect of nedocromil or furosemide alone or in combination on exercise-induced asthma in children.
BACKGROUND: Recent evidence suggests that inhaled nedocromil and furosemide are effective in preventing asthma by ultrasonically nebulized distilled water, allergen, and exercise. There are, however, no studies that compare the effects of these two drugs. The aim of this study was to investigate the effect of inhaled furosemide (30 mg), nedocromil (4 mg), the combination of these two drugs, and placebo aerosol in preventing exercise-induced asthma.
METHODS: Twenty-four children with exercise-induced asthma, aged 6 to 16 years, performed a treadmill test before and 20 minutes after a single dose of drug(s) in a double-blind trial. Lung function measurements were taken before drug administration, before the exercise test (20 minutes after drug administration), and then 2, 4, 6, 8, 10, 15, 20, and 30 minutes after the exercise test.
RESULTS: Both active drugs performed significantly better than placebo. In fact, the exercise challenge resulted in a mean maximum fall in forced expiratory volume in 1 second of 28.46% +/- 13.84% after administration of placebo, but of only 15.42% +/- 8.35% after administration of nedocromil (p < 0.001) and of 11.37% +/- 9.14% after administration of furosemide (p < 0.001). When the two drugs were given together, there was a statistically significant additive effect because the mean maximum fall in forced expiratory volume in 1 second was 5.75% +/- 3.57% (nedocromil vs nedocromil + fluorsemide: p < 0.001; furosemide vs nedocromil + furosemide: p < 0.01).
CONCLUSION: This study suggests that nedocromil and furosemide provide a comparable effect in preventing exercise-induced asthma in children. The combined administration of the two drugs significantly increases the protective effects, suggesting a potential therapeutic use.
Inhibition of exercise-induced-asthma (EIA) by nedocromil sodium and sodium cromoglycate in children.
Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma.
Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air.
This double-blind placebo-crossover study examined the effect of nedocromil sodium, 4 mg aerosol 30 min before challenge, on exercise-induced bronchoconstriction (EIB) in cold air conditions. Twenty-one asthmatic patients (15-28 years), with methacholine PC20 < or = 8 mg/ml in the absence of significant allergen exposure, were randomized to active and placebo therapy on separate study days. Pulmonary function, measured up to 20 min after exercise, showed significantly less deterioration with nedocromil sodium, which effectively halved the maximum percentage decline in forced expiratory volume in the first second. EIB was increased by cold air, whereas an ancillary study in 15 healthy volunteers (18-19 years) showed no such effects. We conclude that prior inhalation of nedocromil sodium diminished cold air-exacerbated EIB in young adult asthmatic patients.
Attenuation of exercise-induced asthma by pretreatment with nedocromil sodium and minocromil.
In a group of atopic adult asthmatic patients the effects of two new inhaled antiasthmatic drugs, nedocromil sodium and minocromil were studied in two independent randomized double-blind trials to assess their efficacy in preventing exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill. Neither drug administered 30 min before exercise significantly altered baseline FEV1. Nedocromil sodium (2 and 4 mg) pre-treatment in nine patients and minocromil (4 mg) in eight patients gave significant protection (P less than 0.001) compared to placebo as assessed by the reduction in the maximum percentage fall in FEV1. There was no significant difference in the inhibitory effect of the two doses of nedocromil sodium. These results indicate that both nedocromil sodium and minocromil can attenuate EIA.
Nedocromil, a mucosal and connective tissue mast cell stabilizer, inhibits exercise-induced asthma.
Nedocromil, the disodium salt of a pyranoquinoline dicarboxylic acid, has a similar profile of activity to disodium cromoglycate (DSCG) but appears to be more active in stabilizing mucosal-type mast cells. In a double-blind placebo-controlled trial nedocromil (2 mg) was given by inhalation to eight asthmatic patients prior to a treadmill exercise task. There was a significant reduction in the fall in FEV1 (P less than 0.01) and FVC (P less than 0.05) after nedocromil when compared to placebo. This study indicates that nedocromil might be an effective anti-asthma agent and in addition may help define the role of the mucosal mast cell.
Nedocromil, a mucosal and connective tissue mast cell stabilizer, inhibits exercise-induced asthma.
Nedocromil, the disodium salt of a pyranoquinoline dicarboxylic acid, has a similar profile of activity to disodium cromoglycate (DSCG) but appears to be more active in stabilizing mucosal-type mast cells. In a double-blind placebo-controlled trial nedocromil (2 mg) was given by inhalation to eight asthmatic patients prior to a treadmill exercise task. There was a significant reduction in the fall in FEV1 (P less than 0.01) and FVC (P less than 0.05) after nedocromil when compared to placebo. This study indicates that nedocromil might be an effective anti-asthma agent and in addition may help define the role of the mucosal mast cell.
Attenuation of exercise induced asthma by nedocromil sodium and sodium cromoglycate.
A randomized double blind cross over trial to compare nedocromil sodium and sodium cromoglycate with placebo in the prevention of exercise induced asthma was conducted. Twenty asthmatics received nedocromil sodium, sodium cromoglycate or placebo via metered dose inhalers on successive days 30 minutes before exercise in a randomized order. Nedocromil sodium and sodium cromoglycate gave sufficient protection (P less than 0.05) compared to placebo as assessed by the reduction in the maximum percentage fall in the forced expiratory volume in 1 second (FEV1). The protective effect of nedocromil sodium and sodium cromoglycate varied in individuals.
Nedocromil sodium in the prevention of exercise-induced bronchospasm in athletes with asthma.
The aim of this study was to determine the efficacy of nedocromil sodium in the prevention of exercise-induced bronchospasm (EIB) in 13 top athletes affected by bronchial asthma. At a dose of 4 mg the drug significantly reduced the fall in FEV1 compared with placebo but not with respect to basal values. In 9 athletes, 4 mg nedocromil sodium produced a good protective effect and reduced the mean fall in FEV1 to 4% with respect to baseline values, while in the remaining 4 subjects, the protective effect was not satisfactory. In these 4 "non responders" 6 mg nedocromil was effective, and in 2 cases induced prolonged bronchodilatation. In conclusion, the effect of nedocromil sodium in the prevention of EIB may be dose-dependent in relation to the degree of bronchial hyperreactivity or to interference of other factors.
A comparative study of the effect of three doses of nedocromil sodium and placebo given by pressurized aerosol to asthmatics with exercise-induced bronchoconstriction.
The effect of placebo and 1 mg, 4 mg, or 8 mg nedocromil sodium, administered 60 minutes prior to treadmill challenge, was determined in a double-blind study of 12 adult asthmatics with reproducible exercise-induced bronchoconstriction. All nedocromil sodium treatments gave significantly smaller falls in PEFR than placebo. Four and 8 mg gave significantly greater protection than 1 mg.
Options:
A: It has no significant effect on exercise-induced bronchoconstriction.
B: It worsens the severity and duration of exercise-induced bronchoconstriction.
C: It reduces the severity and duration of exercise-induced bronchoconstriction, especially in those with severe symptoms.
D: It causes significant adverse effects in individuals with exercise-induced bronchoconstriction.
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C
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83
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the observed effect of inhaled beclomethasone on the linear growth of children with mild-moderate asthma in the reviewed studies? Please answer this question based on the information provided below:
Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate.
Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.
A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group.
BACKGROUND: An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined.
METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed.
RESULTS: During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended.
CONCLUSIONS: Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects.
One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group.
The aim of this study was to compare the effects of salmeterol and beclomethasone on lung function and symptoms in children with mild to moderate asthma. Sixty-seven children not treated with inhaled corticosteroids were randomized in a double-blind parallel study either to salmeterol 50 micrograms b.i.d. or beclomethasone 200 micrograms b.i.d. After one year, FEV1 significantly increased in the beclomethasone group, whereas in the salmeterol group there was a small reduction. Differences between groups were 14.2% predicted (p < 0.0001) and 7.0% predicted (p = 0.007) for pre- and postbronchodilator FEV1 values, respectively. PD20 methacholine decreased by 0.73 DD (p = 0.05) in the salmeterol group and increased by 2.02 DD (p < 0.0001) in the beclomethasone group. Morning and evening PEF and symptom scores improved in both groups, although more in the beclomethasone group. Asthma exacerbations, for which prednisolone was needed, were more frequent in the salmeterol group (17 versus two), as were the number of withdrawals due to exacerbations (six versus one). However, growth was significantly slower in the beclomethasone group (-0.28 SDS) compared with that in the salmeterol group (-0.03 SDS) (p = 0.001). We conclude that treatment with a moderate dose of beclomethasone is superior to salmeterol in children with mild to moderate asthma and recommend that salmeterol should not be used as monotherapy.
Options:
A: Inhaled beclomethasone had no significant effect on the linear growth of children with asthma.
B: Inhaled beclomethasone caused a significant increase in the linear growth of children with asthma.
C: Inhaled beclomethasone caused a significant decrease in the linear growth of children with asthma.
D: Inhaled beclomethasone had variable effects on the linear growth of children with asthma, with no clear trend.
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C
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84
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the effects of tuberculosis treatment regimens lasting less than 6 months compared to longer regimens in terms of relapse rates and adverse reactions? Please answer this question based on the information provided below:
Shortest possible acceptable, effective ambulatory chemotherapy in pulmonary tuberculosis: preliminary report I.
In two 4.5-month regimens and one 3-month regimen the four most potent antituberculous drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) were given for the initial 3 months of chemotherapy. Acceptance by the patients was high, and bacillary sterilization was achieved in 96% of cases within 2 months. Addition of a fifth drug, ethionamide, during the initial 3 months was neither acceptable nor useful. No relapses were observed during a 12-month follow-up period after completion of the 4.5-month regimens. A relapse rate of 5% followed the 3-month regimen. The toxicity and side effects of antituberculous drugs were observed in 16% of patients during the initial 3-month period. In 3.4% of patients, toxicity necessitated cessation of treatment. In the remaining 13% of patients, adverse side effects could be managed without cessation of treatment. Even when patients were ambulatory and outpatient attendance was required for drug administration, the noncompliance rate was only approximately 10%. With the current over-all cost of drugs being limited to 100 United States dollars, the patients with moderately extensive disease must be treated for 100 days, or a maximum of 100 doses.
[Daily ultrashort chemotherapy and intermittent short-term chemotherapy with 4 drugs of communicable pulmonary tuberculosis treated for the first time. Results of a cooperative multicenter study].
Three short-course regimens, all comprising isoniazide (H), rifampicine (R), streptomycine (S) and pyrazinamide (Z), are compared in a randomized prospective cooperative clinical trial. The drugs are given daily in a 3-month regimen (3-HRSZ), twice a week in a 6-month regimen (6-HRSZ2), and in a further two-phase 6-month regimen the 4 drugs are administered 3 times a week for the first 3 months followed by the administration of HSZ twice a week (without R) for further 3 months (3-HRSZ3/3-HSZ2). The number of patients admitted to study is 80, 144 and 139 respectively. The 3-month regimen has been stopped because of a high rate of relapses. 17 p.c. of the patients admitted have to be excluded from analysis for various reasons, out of these 5.8 p.c. because of adverse reactions. Two thirds of the patients had heavily positive sputum cultures at the start. 300 patients completed therapy. At the end of therapy cultures were negative in 94 p.c., 100 p.c. and 99 p.c. respectively. The rate of bacteriological relapses is 19 p.c. in 3-HRSZ, 9 p.c. in 3-HRSZ3/3-HSZ2 and 3 p.c. in 6-HRSZ2, during a follow-up period of 3-4 years after completing therapy. The acceptability was good in all treatment groups. Adverse reactions like "flu" were rarely observed. Increased blood urea was common but in general without clinical symptoms. Elevation of ALAT and ASAT was relatively frequent but mostly transient and without clinical importance. The results served as basis for the new "Recommendation for Treatment of Tuberculosis" and are interpreted with regard to practical consequences and possibilities for further rationalisation of treatment.
Sputum-smear-negative pulmonary tuberculosis: controlled trial of 3-month and 2-month regimens of chemotherapy.
Of 1072 Chinese patients with radiographically active pulmonary tuberculosis and no microscopic evidence of acid-fast bacilli in sputum examinations, only 691 (64%) were sputum-culture negative. All patients were randomly allocated to selective chemotherapy (antituberculosis chemotherapy not being started until the activity of the disease had been confirmed), to daily streptomycin, isoniazid, rifampicin, and pyrazinamide for 2 months or 3 months, or to a standard 12-month control regimen. During the subsequent 12 months, 64% of the patients in the selective chemotherapy series started antituberculosis chemotherapy. Both 2-month and 3-month regimens were inadequate for patients whose pretreatment sputum cultures were positive (relapse-rates 14% and 7%, respectively, in patients with drug-sensitive strains) but in the patients whose first cultures were negative the relapse-rate was only 1% after both short-term regimens.
A controlled trial of 3-month, 4-month, and 6-month regimens of chemotherapy for sputum-smear-negative pulmonary tuberculosis. Results at 5 years. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council.
Of 1,710 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on four or more initial microscopic examinations who were studied for 5 yr, 592 (35%) had one or more initial sputum cultures positive for Mycobacterium tuberculosis. These 592 patients were randomly allocated to receive streptomycin, isoniazid, rifampin, and pyrazinamide daily for 4 months or 3 times a week for either 4 or 6 months. The remaining 1,118 patients with all their initial cultures negative were randomly allocated to receive the same four drugs daily for 3 months or 3 times a week for either 3 or 4 months. There were no bacteriologic failures during chemotherapy, and the relapse rates for the 4-month regimens during the 5 yr were 2% in 293 patients with drug-susceptible cultures initially (95% confidence limits, 1 to 5%); 8% in 59 patients with cultures resistant to isoniazid, streptomycin, or both drugs, but susceptible to rifampin initially; and 4% in 325 patients with all their cultures negative initially (95% confidence limits, 1 to 7%). The combined relapse rate for the 3-month regimens was 7% in 709 patients with all their cultures negative initially (95% confidence limits, 5 to 9%). In Hong Kong, 4 months of chemotherapy is now used routinely in the treatment of patients with smear-negative pulmonary tuberculosis, whether their initial sputum cultures are positive or negative.
Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up.
A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.
Study of chemotherapy regimens of 5 and 7 months' duration and the role of corticosteroids in the treatment of sputum-positive patients with pulmonary tuberculosis in South India.
Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in south India.
A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed, sputum-positive pulmonary tuberculosis. The patients were allocated at random to one of three regimens: a) Rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (R3); b) the same regimen as above but followed by streptomycin, isoniazid and pyrazinamide twice-weekly for a further period of 2 months (R5); c) the same as R5 but without rifampicin (Z5). A bacteriological relapse requiring treatment occurred by 5 years in 16.8% of 113 R3, 5.2% of 97 R5, and 20.0% of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially. The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant (p less than 0.01 for both). Considering patients with organisms initially resistant to streptomycin or isoniazid or both, 7 of 52 patients (4 R3, 2 R5, 1 Z5) had a bacteriological relapse requiring retreatment.
A controlled clinical trial of 3- and 5-month regimens in the treatment of sputum-positive pulmonary tuberculosis in South India. Tuberculosis Research Centre, Madras, and National Tuberculosis Institute, Bangalore.
A controlled comparison of 3 short-course regimens was undertaken in patients with newly diagnosed, sputum-positive, pulmonary tuberculosis in South India. The regimens were: R3: rifampin plus streptomycin plus isoniazid plus pyrazinamide daily for 3 months; 5: the same as regimen R3 followed by streptomycin plus isoniazid plus pyrazinamide twice weekly for 2 months; Z5: the same as regimen R5 but without rifampin. The distributions of various pretreatment characteristics were similar in the 3 series. At the end of treatment, 6 patients (3 R3, 3 Z5) of 694 (228 R3, 230 R5, 236 Z5) with drug-sensitive organisms initially were classified as having an unfavorable response. By 24 months (21 months of follow-up for the R3 regimen and 19 months for the R5 and Z5 regimens), a bacteriologic relapse requiring treatment occurred in 20% of 200 R3, 4% of 187 R5, and 13% of 199 Z5 patients, the difference between the R3 and R5 series being highly significant (p = 0.00001). Considering patients with cultures initially resistant to isoniazid, 4 of 57 in the R3 and R5 series combined had an unfavorable response to treatment compared with 13 of 26 in the Z5 series (p less than 0.0001). Of the 4 patients with an unfavorable response in the R3 and R5 series combined, resistance to rifampin emerged in 2. Complaints of arthralgia were made by 45% of the R3 and R5 patients combined and 70% of the Z5 patients (p less than 0.00001). However, chemotherapy was modified in only 5 and 12%, respectively. Jaundice occurred in 7% of the R3 and R5 patients and 1% of the Z5 patients (p less than 0.00001).
Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis.
In a study in Singapore, Chinese, Malay, and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide followed either by daily treatment with isoniazid, rifampin, and pyrazinamide (SHRZ/HRZ regimen) or by daily administration of isoniazid and rifampin (SHRZ/HR regimen) allocated at random. Both regimens were given for either 6 or 4 months by random allocation. All 330 patients with drug-sensitive tubercle bacilli before treatment had a favorable bacteriologic response during chemotherapy. During the first 6 months after the end of chemotherapy, there was only a single bacteriologic relapse among 84 SHRZ/HRZ and 80 SHRZ/HR patients treated for 6 months, but 8 (10 per cent) of 80 SHRZ/HRZ and 4 (5 per cent) of 74 SHRZ/HR patients treated for 4 months relapsed. Of a total of 33 patients with bacilli resistant to isoniazid, streptomycin, or both drugs before treatment, only one had an unfavorable response during chemotherapy, and none of 31 patients relapsed during the first 6 months after stopping chemotherapy. The incidence of adverse reactions was low; 11 (3 per cent) of 397 patients had hepatitis, but not all episodes were attributable to drug toxicity, and one patient had thrombocytopenic purpura.
Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis: the results up to 30 months.
In a study in Singapore, Chinese, Malay and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin, isoniazid, rifampicin, and pyrazinamide followed by daily isoniazid, and rifampicin either with pyrazinamide (SHRZ/HRZ) or without it (SHRZ/HR), allocated at random. Both regimens were given for either 6 or 4 months by random allocation. All 330 patients with drug-sensitive tubercle bacilli pretreatment had a favourable bacteriological response during chemotherapy. After chemotherapy none of 78 SHRZ/HRZ patients and only 2 of 80 SHRZ/HR patients treated for 6 months relapsed bacteriologically, but 9 (11%) of 79 SHRZ/HRZ and 6 (8%) of 77 SHRZ/HR patients treated for 4 months relapsed. Of 33 patients with bacilli resistant to isoniazid, streptomycin, or both drugs pretreatment, only 1 had an unfavourable response during chemotherapy; none of 9 patients treated for 6 months and 2 of 22 treated for 4 months relapsed bacteriologically after stopping chemotherapy.
Long-term follow-up of a clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council.
In a study in Singapore, patients of Chinese, Malay, or Indian ethnic origin with sputum-smear-positive pulmonary tuberculosis received 2 months of daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide followed by daily isoniazid and rifampin, either with or without pyrazinamide, allocated at random. Both regimens were given for a total duration of either 6 or 4 months by random allocation. As previously reported, all 330 patients with drug-susceptible strains of tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy, and only 2 (1%) of 158 in the 6-month series, compared with 15 (10%) of 156 in the 4-month series, relapsed bacteriologically during the 30 months after the start of chemotherapy. A long-term follow-up assessment has been conducted 5 to 8 yr after admission to the study. The excellent results in the 6-month series were maintained; only 1 of the 138 patients assessed relapsed after 30 months, compared with 5 of the 131 in the 4-month series. Of 33 patients with bacilli resistant to isoniazid, streptomycin, or both drugs pretreatment, 1 had an unfavorable response during treatment, and none of 9 in the 6-month series and 2 of 22 in the 4-month series relapsed bacteriologically by 30 months, but none of the nine 6-month and eighteen 4-month patients assessed relapsed subsequently.
Options:
A: Shorter regimens result in significantly higher relapse rates and more adverse reactions.
B: Shorter regimens result in significantly higher relapse rates but similar rates of adverse reactions.
C: Shorter regimens result in similar relapse rates and fewer adverse reactions.
D: Shorter regimens result in lower relapse rates and fewer adverse reactions.
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B
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85
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effect of 6 and 12 month courses of isoniazid (INH) for preventing tuberculosis (TB) in HIV-negative people at increased risk of developing active TB? Please answer this question based on the information provided below:
Isoniazid prophylaxis in an undeveloped area.
Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies.
As a result of numerous trials, isoniazid prophylaxis was shown to be effective in preventing tuberculosis in many different populations and under a variety of conditions. However, the duration of the protective effect has been of some concern. In a previous report, the protective effect of isoniazid prophylaxis among Alaskan Eskimos was shown to persist through the fifteenth year after its administration. In this final report, the protective effect is shown to persist for more than 19 years. The magnitude of the effect is related to the amount of isoniazid taken. The results of the study are consistent with the hypothesis that the decrease in risk of tuberculosis produced by isoniazid preventive therapy is lifelong.
A controlled trial of community-wide isoniazid prophylaxis in Alaska.
Isoniazid prophylaxis among Alaskan Eskimos: a progress report.
The use of isoniazid among household contacts of open cases of pulmonary tuberculosis.
A controlled and double-blind study to determine the efficacy of isoniazid in preventing the development of pulmonary tuberculosis among the household contacts of open cases of the disease has been carried out in a rural area of Kenya-a financially handicapped country-under realistic field conditions.A one-year course of isoniazid (5-10 mg per kg of body-weight in one daily dose) administered to the contacts of active cases gave a reduction in respect of the excretion of tubercle bacilli of the order of 90% at the end of the year. In the subsequent observation period (2-4 years) both the control and the isoniazid-treated group showed a low and similar rate of adverse findings.Previous studies by the Tuberculosis Chemotherapy and BCG Centre, Nairobi, had revealed that the risk of tuberculosis among household contacts, especially children, was high and, further, that the acceptability of the drug and the regularity of drug-taking were poor among these contacts. Even so, a very considerable prophylactic effect of isoniazid was demonstrated in the present study. It therefore seems justifiable to conclude that the treatment of household contacts with isoniazid could contribute to tuberculosis control in financially handicapped countries, particularly where a tuberculosis case-finding programme is reasonably well established.
Prophylaxis with isoniazid in inactive tuberculosis. A Veterans Administration Cooperative Study XII.
Based on a study indicating a significant rate of reactivation of tuberculosis in Veterans Administration patients with inactive disease, a cooperative study was initiated to determine the prophylactic effect of isoniazid on the rate of reactivation. A randomized double-blind study was designed, utilizing three regimens, two with isoniazid and one with placebo only. Two consecutive years of taking pills in one of the three regimens was followed by five years of observation. A total of 7,036 patients with inactive disease, some of whom had received prior chemotherapy, were entered into the study. Only 63 reactivations of tuberculosis were found, for a total rate of reactivation of 9/1,000 (less than 1%) over the seven-year period. Although no significant differences in the rate of reactivation were found among any of the regimens, there was a significant reduction in the rate of reactivation among those who had not received any prior chemotherapy and received isoniazid (INH) in this study, compared with those who received placebo only.
Tuberculosis morbidity in a controlled trial of the prophylactic use of isoniazid among household contacts.
A CONTROLLED TRIAL OF ISONIAZID PROPHYLAXIS IN MENTAL INSTITUTIONS.
A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council.
A double-blind placebo-controlled trial of antituberculosis chemoprophylaxis was undertaken in sillicotic subjects in Hong Kong where there is a high prevalence of both silicosis and tuberculosis. During 1981 to 1987, 679 Chinese men with silicosis, with no history of previous antituberculosis chemotherapy and no evidence of active tuberculosis, were admitted to the trial and have been studied for between 2 and 5 yr. They were allocated at random to four series-rifampin for 12 wk (R3), isoniazid and rifampin for 12 wk (HR3), isoniazid alone for 24 wk (H6), or placebo (Pl)--in a double-blind design with matching placebos for isoniazid and rifampin as appropriate. Active pulmonary tuberculosis developed more frequently during the 5 yr in the placebo series than in the three chemoprophylaxis series (p less than 0.01, log-rank test), but there were no significant differences between the chemoprophylaxis series. The estimated proportions of patients with active pulmonary disease in the placebo series were 9% at 2 yr, 15% at 3 yr, 20% at 4 yr, and 27% at 5 yr. In contrast, in the three chemoprophylaxis series combined they were 5, 8, 10, and 13%, respectively. Thus, although chemoprophylaxis halved the proportion of patients in whom tuberculosis developed, this proportion was still substantial. There was no evidence that chemoprophylaxis led to the selection of drug-resistant strains of bacilli. Adverse effects were reported with a similar frequency in all four series, suggesting that few were drug related. During the first 12 wk, hepatic toxicity was reported in 8 (1%) patients (3 HR3, 3 H6, and 2 Pl), but only 1 (H6) had symptomatic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
A double-blind randomized controlled trial of primary isoniazid prophylaxis in dialysis and transplant patients.
The effect of isoniazid prophylaxis on tuberculosis morbidity among household contacts of previously known cases of tuberculosis.
The IUAT trial on isoniazid preventive treatment in persons with fibrotic lung lesions.
Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis.
A total of 28 000 persons with fibrotic pulmonary lesions compatible with tuberculosis were followed for five years after receiving 12, 24, or 52 weeks of preventive treatment with isoniazid or placebo.Compared with placebo, 12 weeks of isoniazid eliminated less than one-third, and 24 weeks eliminated two-thirds of the tuberculosis risk. Where preventive treatment is not currently practised, adopting a 24-week regimen could decrease the incidence of tuberculosis in such populations by 65%.Hepatitis, the only serious side-effect encountered, occurred infrequently but was more common among isoniazid recipients (0.5%) than among placebo recipients (0.1%).Fifty-two weeks of isoniazid prevented the most tuberculosis, but 24 weeks prevented more tuberculosis cases per case of hepatitis caused. Where preventive treatment is currently practised for 52 weeks, adopting a 24-week regimen would decrease hepatitis by one-third and increase tuberculosis by 40%.
Long term isoniazid prophylaxis. Controlled trial on INH prophylaxis after recent tuberculin conversion in young adults.
Options:
A: Both 6 and 12 month courses of INH significantly reduce the risk of developing active TB, with no significant difference between the two durations.
B: Only the 12 month course of INH significantly reduces the risk of developing active TB, while the 6 month course does not.
C: Neither the 6 month nor the 12 month course of INH significantly reduces the risk of developing active TB.
D: Both 6 and 12 month courses of INH significantly reduce the risk of developing active TB, with the 12 month course being significantly more effective.
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A
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86
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the use of iron-chelating agents combined with antimalarial drugs for treating Plasmodium falciparum malaria in terms of mortality, coma recovery time, parasite clearance, and adverse effects? Please answer this question based on the information provided below:
Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.
To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.
Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria.
BACKGROUND: Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy.
METHODS: To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis.
RESULTS: The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52).
CONCLUSIONS: Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.
The antimalarial effect of iron chelators: studies in animal models and in humans with mild falciparum malaria.
In this study we explore the antimalarial effects of 3-hydroxypyridin-4-ones (CP compounds), a family of bidentate orally effective iron chelators in experimental animal systems in vivo and in vitro, and examine whether the iron chelator deferoxamine (DF) is active against human infection with P. falciparum. There was direct relation between lipid solubility of the CP compounds, which would facilitate membrane transit, and their in vivo antimalarial action, suggesting direct intracellular iron chelation as the most likely explantation for the antimalarial effect of iron chelators. Results of the double-blind, placebo controlled trial of DF in humans with asymptomatic parasitemia provided unequivocal evidence that this iron-chelating agent has antimalarial activity. Depriving the parasite of a metabolically important source of iron may represent a novel approach to antimalarial drug development. DF is a relatively ineffective intraerythrocytic chelator, and our data indicate that other orally effective iron chelators may have superior antimalarial activity in vivo. A systematic screening of available iron chelating drugs may result in the identification of potentially useful antimalarial compounds.
Iron chelation as a chemotherapeutic strategy for falciparum malaria.
To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo. Over seven days of observation, mean parasite concentrations remained at the initial levels in six individuals originally given placebo, but decreased promptly with administration of desferrioxamine B (P = 0.001). Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the eight who had received placebo only (P = 0.027). We conclude that iron chelation has antiplasmodial activity and may offer a new therapeutic strategy for falciparum malaria.
Deferiprone (L1) as an adjuvant therapy for Plasmodium falciparum malaria.
BACKGROUND & OBJECTIVES: Mortality due to Plasmodium falciparum infection remains high in India, hence any modality of treatment which can improve the outcome of this disease is worth exploring. The present study was undertaken to see whether addition of an oral iron chelator, deferiprone (L1) to the conventional treatment regime for P. falciparum infection improves the clinical course and final outcome.
METHODS: In this prospective, randomised double blind trial, 45 consecutive patients with P. falciparum infection were randomised into two groups. Patients in Group I (control group, 21 patients) received standard quinine and doxycycline therapy along with supportive therapy and placebo capsules for 10 days. Patients in Group II (24 patients) received the same treatment as Group I but in place of placebo capsule received deferiprone capsules 75 mg/kg/day in 12 hourly divided doses. The parameters evaluated included the time taken in resolution of parasitaemia, fever and coma, differences in final outcome i.e., death or other severe complications, and side effects and deferiprone tolerance.
RESULTS: Four patients in Group I and two in Group II died (P > 0.05). The resolution of fever and coma was significantly faster in Group II (P < 0.05) and parasitaemia cleared 24 h earlier in this Group. The drug was well tolerated and had no side effects.
INTERPRETATION & CONCLUSION: Deferiprone (L1) seems to be a promising agent as an adjuvant in the treatment for severe P. falciparum malaria infection.
Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.
To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.
Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.
While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone-associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action.
Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.
While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone-associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action.
Options:
A: Iron-chelating agents significantly reduced mortality and improved coma recovery time and parasite clearance without increasing adverse effects.
B: Iron-chelating agents showed no evidence of benefit or harm in terms of mortality, but reduced the risk of persistent seizures, with many adverse effects being more common.
C: Iron-chelating agents significantly increased mortality and had no impact on coma recovery time, parasite clearance, or adverse effects.
D: Iron-chelating agents had no impact on mortality, coma recovery time, parasite clearance, or adverse effects.
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B
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87
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the effects of routine blood transfusion for severe anaemia in children in malarious areas? Please answer this question based on the information provided below:
Management of severe malarial anaemia in Gambian children.
The optimum management of children with severe malarial anaemia is still uncertain. Hence, we have undertaken a study to determine whether iron treatment is as effective at restoring haemoglobin levels one month after presentation as blood transfusion without iron treatment in children with moderately severe malarial anaemia. Two hundred and eighty-seven children with a packed cell volume (PCV) < 15% and malaria infection were recruited into the study; 173 children were assigned to receive blood transfusion because they had a PCV < 12% and/or signs of respiratory distress and the remaining 114 children were allocated at random to receive either blood transfusion (58) or treatment with oral iron (56) for 28 d. Twenty-four children died, 23 in the most severely anaemic group. Fifteen children (65%) died before transfusion was given and most deaths occurred within the first 4 h of admission. One child died in the iron treatment group and 10 subsequently required transfusion. Among the severely anaemic children, those with respiratory distress were at greater risk of death than those without respiratory distress. After 28 d, haematological restoration was significantly better in children who had received iron than in those treated by blood transfusion (P = 0.02). Children who received malaria chemoprophylaxis after discharge from hospital had fewer episodes of malaria and subsequent admissions to a hospital or health centre than those who did not. Children with severe anaemia and clinical signs of respiratory distress must be identified quickly and transfused as soon as possible. However, for less severely anaemic children who are clinically stable, iron therapy offers an alternative to transfusion provided such children can be kept under surveillance and transfused subsequently should this become necessary.
Childhood anemia in Africa: to transfuse or not transfuse?
Blood transfusions are an important route for HIV transmission in Africa. To explore whether transfusions are necessary in the case management of childhood anemia, a randomized trial was performed in Ifakara, Tanzania, a holoendemic malaria region. 116 children were randomized to receive either treatment for malaria and hookworm alone or, in addition, a transfusion of whole blood which had been tested negative for antibodies against the human immunodeficiency virus. Mean packed cell volume (PCV) at admission was 14.0% in the transfusion and 14.4% in the no transfusion group. Children were followed up for 8 weeks with measurements of PCV at 2 days, 4 weeks and 8 weeks after study entry. PCV was similar in both groups after 4 and 8 weeks (22.9% in the transfusion and 23.6% in the no transfusion group). There was a trend towards more hospital admissions and deaths in the no transfusion group; however, 95% confidence intervals included both a beneficial and an adverse effect of blood transfusions. The costs and benefits of transfusion for childhood anemia in countries with a high HIV prevalence need to be considered carefully before a rational treatment policy can be adopted. For that purpose, a larger randomized trial is urgently needed.
Options:
A: Routine blood transfusion significantly reduced the risk of death and increased haematocrit levels at one month.
B: Routine blood transfusion showed a non-significant tendency towards fewer deaths but significantly more severe adverse events.
C: Routine blood transfusion had no impact on the risk of death and did not affect the haematocrit levels at one month.
D: Routine blood transfusion significantly increased the risk of death and decreased haematocrit levels at one month.
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B
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88
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effect of intravenous magnesium sulfate on patients with acute asthma managed in the emergency department? Please answer this question based on the information provided below:
Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma.
STUDY OBJECTIVE: This study was conducted to determine whether intravenous magnesium sulfate (MgSO4), when used as part of a standardized treatment protocol, can improve pulmonary function and decrease admission rate in patients presenting to the emergency department with exacerbations of asthma.
DESIGN: In this randomized double-blind placebo-controlled study, patients with acute asthma were treated with inhaled beta-agonists at regular intervals and intravenous (IV) steroids. At 30 min after entry, patients received either 2 g IV MgSO4 or IV placebo. Patients were monitored for up to 4 h with regular measurements of pulmonary function. Patients who were discharged from the emergency department were contacted at 1 day and 7 days for follow-up.
SETTING: Emergency departments of a university-affiliated, voluntary hospital and municipal hospital.
PARTICIPANTS: Asthmatics aged 18 to 65 years during acute exacerbation with FEV1 less than 75% predicted both before and after a single albuterol treatment.
INTERVENTIONS: Patients were given 2 g of MgSO4 or placebo as an adjunct to standardized emergency department procedure for acute asthma.
MEASUREMENTS AND RESULTS: One hundred thirty-five patients were studied. Hospital admission rates were 35.3% for placebo-treated group and 25.4% for the magnesium-treated group (p = 0.21). FEV1 measured at 120 min was 56% predicted for the placebo-treated group and 55% predicted for the magnesium-treated group. (p = 0.92) For subgroup analysis, patients were divided into "severe" (baseline FEV1 < 25% predicted on presentation) or "moderate" (baseline FEV1, 25 to 75% predicted on presentation). For the severe group, admission rates were 78.6% (11/14) for the placebo-treated group and 33.3% (7/21) for the magnesium-treated group (p = 0.009). For the moderate patients, admission rates were 22.4% (11/49) for the placebo-treated group and 22.2% (10/25) for the magnesium-treated group (p = 0.98). There was no significant improvement in FEV1 in the moderate group for magnesium-treated patients. However, in the severe group, there was a significant improvement in FEV1 at 120 min and 240 min (p = 0.014 and 0.026, respectively).
CONCLUSION: Intravenous MgSO4 decreased admission rate and improved FEV1 in patients with acute severe asthma but did not cause significant improvement in patients with moderate asthma.
Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial.
OBJECTIVE: To evaluate the efficacy of intravenous magnesium (IVMg) therapy for moderate to severe asthma exacerbations in pediatric patients.
DESIGN: Randomized, double-blind, placebo-controlled, clinical trial.
SETTING: Urban pediatric emergency department.
PARTICIPANTS: Thirty-one patients aged 6 to 18 years who were being treated for an acute asthma exacerbation with peak expiratory flow rate (PEFR) less than 60% of the predicted value after receiving three beta 2-adrenergic nebulizer treatments.
INTERVENTIONS: Magnesium sulfate infusion, 25 mg/kg (maximum, 2 gm), or equivolume saline solution for 20 minutes.
MEASUREMENTS AND RESULTS: Vital signs, O2 saturation by pulse oximetry, PEFR, forced vital capacity, forced expiratory volume at 1 second, and physical examination were serially recorded for 110 minutes, with serum magnesium concentrations measured before and after the 20-minute infusion. At 50 minutes the magnesium group had a significantly greater percentage of improvement from baseline in forced expiratory volume at 1 second (34% vs -1%; p = 0.05); this improvement was sustained and even greater at 110 minutes (75% vs 5%; p = 0.01). Results were similar for PEFR at 80 through 110 minutes (59% vs 20% at 110 minutes; p = 0.05) and for forced vital capacity (55% vs 8% at 80 minutes; p = 0.05). There were no significant intergroup differences in blood pressure at any point. Patients who received intravenous magnesium infusions were more likely to be discharged home from the emergency department than those who received placebo (4/15 vs 0/16; p = 0.03).
CONCLUSIONS: Children treated with intravenous magnesium infusions for moderate to severe asthma had significantly greater improvement in short-term pulmonary function without any significant alteration in blood pressure, suggesting a role for this agent as an adjunct in the treatment of such patients.
Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy.
OBJECTIVE: To evaluate the effectiveness of early administration of intravenous Magnesium sulfate (i.v. MgSO4) in children with acute severe asthma not responding to conventional therapy.
DESIGN: Randomized double-blind, placebo-controlled trial.
SETTING: Pediatric emergency service of a large teaching hospital.
SUBJECTS: 47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each.
INTERVENTION: The MgSO4 group received 0.2 ml/kg of 50% MgSO4 as intravenous (i.v.) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients received oxygen, nebulized salbutamol, i.v. aminophylline and corticosteroids.
RESULTS: MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours after stopping the infusion (p ranging from < 0.05 to < 0.01). The clinical asthma score also showed significant improvement in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion (p < 0.01).
CONCLUSION: Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone.
Intravenous magnesium for acute asthma: failure to decrease emergency treatment duration or need for hospitalization.
STUDY OBJECTIVE: To evaluate the efficacy of routine early administration of i.v. magnesium to patients with acute asthma.
DESIGN: Prospective, randomized clinical trial.
SETTING: Urban teaching hospital emergency department.
TYPE OF PARTICIPANTS: One hundred twenty consecutive patients aged 18 to 65 years with acute asthma unresponsive to a single albuterol treatment.
INTERVENTIONS: All patients received oxygen, 125 mg i.v. methylprednisolone, and hourly albuterol inhalation therapy. The study group also received 2 g i.v. magnesium sulfate infused over 20 minutes.
MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics were similar in both groups. Hospitalization was necessary in 13 of 58 patients who received magnesium (22%; 95% confidence intervals [CI], 13% to 32%) and 11 of 62 control patients (17%; 95% CI 10% to 26%; P = .523). Duration of ED treatment in discharged patients was 224 +/- 75 minutes in the magnesium group (95% CI, 208 to 240 minutes) and 228 +/- 90 minutes in the control group (95% CI, 209 to 247 minutes, P = .832). In addition, changes in peak expiratory flow were not statistically different.
CONCLUSION: Routine early administration of IV magnesium in acute asthma does not alter treatment outcome.
Intravenous magnesium sulfate for the treatment of acute asthma in the emergency department.
Conventional nebulized beta-agonist therapy has met with disappointing results in an increasing number of moderate to severe asthmatics who may be characterized as "poor responders." Thirty-eight patients suffering from acute exacerbations of moderate to severe asthma were treated in an emergency department with an intravenous infusion of saline placebo or 1.2 g of magnesium sulfate after conventional beta-agonist therapy failed to produce significant improvement in peak expiratory flow rate. Nineteen patients were randomized into each of two groups in a placebo-controlled, double-blind clinical trial. The treatment group demonstrated an increase in peak expiratory flow rate from 225 to 297 L/min as compared with 208 to 216 L/min seen in the placebo group. In addition, the number admitted vs discharged was significantly better for the treatment group (7 vs 12) than the placebo group (15 vs 4). Intravenous magnesium sulfate may represent a beneficial adjunct therapy in patients with moderate to severe asthma who show little improvement with beta-agonists.
Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations.
HYPOTHESIS: Intravenous magnesium sulfate improves objective measures of expiratory flow in patients with acute severe exacerbations of asthma.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: Urban emergency department.
PARTICIPANTS: Forty-eight asthmatic patients aged 18 to 60 years with initial peak expiratory flow rate (PEFR) < 200 L/min who failed to double their initial PEFR after two standardized albuterol treatments.
INTERVENTIONS: Subjects were randomized to three groups: a loading dose of magnesium sulfate, 2 g IV over 20 min followed by 2 g/h over 4 h (infusion), magnesium sulfate, 2 g over 20 min followed by placebo infusion (bolus), or placebo loading dose and infusion (placebo). All subjects received standardized aminophylline and steroid therapy.
MEASUREMENTS: The PEFR and FEV1 were measured at the start of the loading dose, and 20, 50, 80, 140, 200, and 260 min later using a water-displacement spirometer. Changes from baseline were compared by one-way analysis of variance for repeated measures.
RESULTS: Magnesium sulfate administration did not at any time significantly improve either FEV1 (F = 0.036, p = 0.96) or PEFR (F = 0.51, p = 0.61). This study had the power to detect a PEFR difference of 26 L/min and a FEV1 difference of 0.19 L between groups (beta = 0.20, alpha = 0.05 two-tailed significance).
CONCLUSION: Use of IV magnesium sulfate in addition to standard therapy does not provide clinically meaningful improvement of objective measures of expiratory flow in patients with moderate to severe asthma exacerbations.
Options:
A: Intravenous magnesium sulfate significantly improves peak expiratory flow rates in all patients with acute asthma.
B: Intravenous magnesium sulfate significantly reduces hospital admissions in all patients with acute asthma.
C: Intravenous magnesium sulfate is beneficial and reduces hospital admissions in patients with severe acute asthma.
D: Intravenous magnesium sulfate causes significant adverse side effects in patients with acute asthma.
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C
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89
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the main findings regarding the clinical effects and adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD patients? Please answer this question based on the information provided below:
Efficacy of inhaled metaproterenol and orally-administered theophylline in patients with chronic airflow obstruction.
To evaluate comparative bronchodilator efficacy with chronic airflow obstruction (CAO), we randomly administered to ten patients week-long treatments consisting of: inhaled metaproterenol from a metered dose canister (1.30 mg six times a day) and doses of a sustained-release theophylline formulation sufficient to achieve plasma levels of 10-15 micrograms/ml; metaproterenol-placebo; theophylline-placebo; or placebo-placebo. At the end of each period, treatment responses were evaluated by spirometric tests, by exercise tolerance (12 minute walk and progressive cycle ergometry) and by subjective perception of dyspnea (oxygen cost diagram and breathlessness rating). Metaproterenol as a single treatment caused statistically significant improvements in spirometric variables and in the breathlessness rating. Theophylline as a single treatment caused significant changes in none of the test variables, though favorable trends were observed. Combined drug therapy was significantly better than metaproterenol only in the case of the breathlessness rating. We conclude that in the treatment of patients with CAO, inhaled metaproterenol is superior to oral theophylline. Our results permit no definite conclusion concerning added benefits of combined drug therapy.
Bronchodilators in chronic air-flow limitation. Effects on airway function, exercise capacity, and quality of life.
We conducted a trial of inhaled salbutamol and orally administered theophylline in patients whose acute response to inhaled salbutamol was less than 25% of their baseline FEV1. Patients underwent 4 treatment periods, each of 2 wk duration, during which they received the following combinations: placebo-placebo, placebo-salbutamol, placebo-theophylline, and salbutamol-theophylline. The 19 patient who completed the study were all males with a mean age of 65 +/- 7.4 yr, mean FEV1 of 1.02 +/- 0.38, and mean VC of 2.73 +/- 0.19. Outcomes included twice-daily recordings of peak flow rates, spirometry, the distance patients could walk in 6 min, and clinical symptoms of dyspnea, fatigue, and emotional function. Clinically important and statistically significant differences between the 4 periods were noted on both physiologic and functional outcomes. For the group as a whole, improvement with inhaled salbutamol and orally administered theophylline was comparable, and additional benefit was gained from a combination of the 2 drugs. We conclude that both inhaled salbutamol and orally administered theophylline can improve airflow obstruction, functional exercise capacity, and quality of life in patients with primarily fixed air-flow limitation.
Acute response to bronchodilator. An imperfect guide for bronchodilator therapy in chronic airflow limitation.
We conducted a four-period cross-over randomized trial in which we found that patients with chronic airflow limitation demonstrated symptomatic improvement with both inhaled albuterol and oral theophylline. The response, however, was not uniform. We therefore tested the ability of acute change in forced expired volume in one second (FEV1) following inhaled beta agonist to predict long-term symptomatic response to albuterol and theophylline. We found that the reproducibility of acute change in FEV1 over three repetitions was poor (intraclass correlation 0.17). Furthermore, the mean improvement FEV1 following inhaled albuterol across the three repetitions did not relate closely to symptomatic response to either albuterol or theophylline. We conclude that acute response to inhaled beta agonist is not useful for identifying patients with chronic airflow limitation who are likely to benefit from bronchodilator treatment.
Should study subjects see their previous responses: data from a randomized control trial.
To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire (the Chronic Respiratory Disease Questionnaire, or CRQ) in a randomized, double-blind trial of bronchodilators in chronic airflow limitation. The responsiveness of the two methods, as reflected in the p-values associated with salbutamol and theophylline effects were comparable for three of the four dimensions of the CRQ. The data suggested possible increased responsiveness of the informed method for the emotional function dimension of the questionnaire. Changes in the informed CRQ dyspnea and fatigue dimensions showed stronger correlations with changes in spirometry, 6 minute walk distance, and rating of dyspnea after the walk test than did blind administration. Further, changes in all four CRQ dimensions showed stronger correlations with corresponding global ratings using the informed questionnaire. These results suggest that by letting study subjects see their previous responses the validity of subjective measures of health status in clinical trials can be improved.
Domiciliary nebulized terbutaline in severe chronic airways obstruction.
Forty-eight patients with severe chronic airways obstruction were given 5 mg terbutaline or placebo from a nebulizer twice daily for 2 + 2 weeks. Twenty three patients preferred terbutaline, 9 placebo and 16 had no preference. The baseline lung function and the 6 minute walking distance were not increased after the terbutaline period. The patients who preferred terbutaline indicated less dyspnoea after the terbutaline period as compared to the placebo period, but did not differ with regard to lung function or walking distance after the terbutaline treatment. The physiology behind the subjective relief from the terbutaline inhalations remains unexplained.
Mechanism of bronchodilator effect in chronic airflow limitation.
OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities.
METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined.
RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001).
CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.
A comparative study of atropine sulfate and isoproterenol hydrochloride in chronic bronchitis.
Fifteen subjects with chronic bronchitis were treated with inhaled atropine sulfate, isoproterenol hydrochloride, or placebo in a double blind crossover trial. Each drug was inhaled 4 times per day for 3 weeks. Baseline forced expiratory flows, specific airway conductance, airway resistnace, and functional residual capacity were measured weekly. These measurements were repeated 15 min and 60 min after laboratory inhalation of each agent, using a separate double blind protocol. No significant differences were observed among the mean baseline function studies during the 3 treatment periods. There were no significant differences in sputum production, sputum thickness, dyspnea, or mouth dryness among the 3 treatment periods. Side effects were mild; isoproterenol treatment was associated with an increased frequency of palpitations, and atropine treatment was associated with difficulty in voiding. Significant increases in lung function were apparent in the measurements made 15 min and 60 min after inhalation of atropine or isoproterenol. Mean values of flow and specific airway conductance increased, and mean values of airway resistance and functional residual capacity decreased after inhalation of either drug. There was no significant difference between the effects of atropine and isoproterenol on lung function, although both differed significantly from the effects of placebo (P less than 0.001). Inhaled atropine sulfate was as effective a bronchodilator as inhaled isoproterenol hydrochloride, and was well tolerated during the 3-week trial of daily therapy.
Response of patients with chronic obstructive lung disease to the regular administration of nebulized isoproterenol. A double-blind crossover study.
The effect of the regular use of neublized isoproterenol in 14 patients with symptomatic chronic obstructive lung disease (COLD) was evaluated in a double-blind crossover 16-week study. FEV1, FVC and SGaw were measured before and 45 minutes after bronchodilator therapy every two weeks, while arterial blood gases were measured every eight weeks, before and 45 minutes after bronchodilator therapy. When the patients were considered as a group, there was no significant difference in mean symptom scores or objective pulmonary functions during the drug and placebo periods. Four patients had significantly higher (p less than .05) and two patients significantly lower mean values for at least one of the pulmonary function tests during the isoproterenol period. The patient who is most likely to benefit from isoproterenol on a regular basis appears to have the following characteristics; (1) consistent improvement in pulmonary function tests 45 minutes after use of nebulized bronchodilator; (2) moderate rather than severe COLD; and (3) a relatively normal DLCO.
Breathlessness and exercise tolerance in chronic airflow obstruction: 2-hourly versus 4-hourly salbutamol by inhalation.
Breathlessness, exercise tolerance, and spirometry were measured in 12 patients whose major symptom was breathlessness, secondary to severe chronic airflow limitation, during a double-blind crossover comparison of inhaled salbutamol in two dosages (200 micrograms 4-hourly and 200 micrograms 2-hourly) with placebo. Daily visual analogue scores of breathlessness, exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo. The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance. Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time, without side-effects. Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation.
Evaluation of domiciliary treatment with terbutaline by wet nebulisation in patients with chronic bronchitis and emphysema.
Domiciliary treatment with terbutaline by wet nebulisation (5 mg, four times daily) was compared with placebo in a double-blind study over four consecutive periods, each of seven days duration, in eight patients with severe airflow limitation due to chronic bronchitis and emphysema. Lung function tests performed at the conclusion of each treatment period showed small but significant improvements in FEV1 before and after 500 micrograms of terbutaline by metered dose inhaler (MDI), with reductions in functional residual capacity and residual volume for terbutaline compared with placebo. Morning and evening peak expiratory flow rate recordings were greater and there was a significant reduction in the use of terbutaline by MDI during the terbutaline treatment. Three patients were unable to complete the placebo treatment because of excessive symptoms. Analysing all individual results, only one patient appeared not to benefit from nebulised terbutaline, while the preference rating for the other seven patients was significantly in favour of terbutaline.
Bronchodilator treatment for partially reversible chronic obstructive airways disease.
The effect of six weeks' treatment with inhaled terbutaline (1 mg four times a day), optimised doses of theophylline (twice a day), the combination of theophylline and terbutaline, and placebo was studied in a randomised, double blind, crossover trial. Thirty patients with partially reversible chronic airflow obstruction and a mean forced expiratory volume in one second (FEV1) of 1.2 litres that improved by 25% were included in the study. Patients who developed non-infective exacerbations of airflow obstruction that required additional bronchodilator treatment were classed as "treatment failures." Such treatment failure occurred in 23 patients with placebo, in 22 patients with theophylline, in 12 patients with terbutaline, and in two patients taking the two drugs. Mean daily peak flow readings were highest with the combination of the two drugs, followed by terbutaline and then theophylline, and lowest with placebo. Thus a combination of terbutaline and theophylline was superior to either drug alone; inhaled terbutaline was superior to theophylline alone. Theophylline alone does not appear to have much place in the management of patients with partially reversible obstructive airways disease.
The efficacy of orally administered theophylline, inhaled salbutamol, and a combination of the two as chronic therapy in the management of chronic bronchitis with reversible air-flow obstruction.
The efficacy of bronchodilator therapy was assessed in the long-term management of patients with chronic bronchitis and varying degrees of reversible air-flow obstruction. Twenty-five patients with a mean forced expiratory volume in one second (FEV1) 38.7% predicted received: optimized doses of orally administered, sustained-release theophylline, inhaled salbutamol (200 micrograms 4 times a day), a combination of the 2 drugs, and identical placebo therapy for periods of 3 wk in a randomized, double-blind, crossover trial. Patients who deteriorated during treatment were assessed immediately and designated "treatment failures" if additional therapy proved necessary. Such "failures" occurred in 9 patients with placebo, in 8 with salbutamol, in 6 with theophylline, and in only 1 with combined therapy. Using a ranking system based on "treatment failures" and mean daily peak flow rates, first preference was given to combined therapy in 13 patients, theophylline in 6, salbutamol in 4, and placebo in 2. Thus, both combined therapy (p less than 0.001) and theophylline (p less than 0.05) were better than placebo, but this was not so for inhaled salbutamol. Objective improvements in FEV1 and forced vital capacity were a consistent finding with combined therapy compared with placebo, although not with single agents, and additive effects were clearly demonstrated. In the subgroup of patients able to tolerate placebo therapy, no subjective benefit could be discerned during any of the 3 periods of active treatment. Thus, the combination of orally administered, sustained-release theophylline and inhaled salbutamol offered significant advantages in the clinical control of patients with chronic bronchitis with air-flow obstruction.
Domiciliary nebulised salbutamol solution in severe chronic airway obstruction.
Nine patients with severe chronic airway obstruction secondary to chronic bronchitis and emphysema all preferred nebulised salbutamol solution to placebo in a double-blind controlled trial. Four of the patients who had previously received domiciliary nebulised salbutamol failed to complete the placebo period, though all completed the active period. Five others improved subjectively on active therapy, and showed a significant improvement in morning and evening peak flows. Symptom scores for breathlessness, wheezing, and sputum production were lower in the active treatment period and standard aerosol usage fell, although these changes might have been due to chance. Patients with severe chronic airway obstruction who do not respond to conventional bronchodilator therapy should be considered for this form of treatment.
Options:
A: Inhaled short-acting beta 2 agonists significantly improved FEV1, FVC, and PEFR, and reduced breathlessness compared to placebo, but had no significant effect on FRC, airway resistance, or walking distance.
B: Inhaled short-acting beta 2 agonists had no significant effect on FEV1, FVC, PEFR, breathlessness, FRC, airway resistance, or walking distance compared to placebo.
C: Inhaled short-acting beta 2 agonists significantly improved FEV1, FVC, PEFR, breathlessness, FRC, airway resistance, and walking distance compared to placebo.
D: Inhaled short-acting beta 2 agonists significantly improved FEV1, FVC, and PEFR, but had no significant effect on breathlessness, FRC, airway resistance, or walking distance compared to placebo.
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A
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90
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the overall conclusion regarding the effectiveness of treatments for gastro-oesophageal reflux on asthma in adults and children? Please answer this question based on the information provided below:
No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux.
Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway hyperresponsiveness through vagally-mediated pathways. We wanted to determine whether elimination of acid reflux could improve symptoms in such patients. In a randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and severe airway hyperresponsiveness despite maintenance treatment with an inhaled corticosteroid and with increased acid gastro-oesophageal reflux, were treated either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints were: airway hyperresponsiveness, as determined by the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow variability; reversibility to inhaled ipratropium bromide as a parameter of vagal activity; asthma symptoms scores; and medication used. Reflux was measured by 24 h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3 months had no beneficial effect on any of the pulmonary parameters, despite its profound effect on acid reflux and improvement of reflux symptoms scores, compared to placebo. The results of this study do not support a role for intensive antireflux therapy to improve pulmonary symptoms and function in patients with asthma and chronic obstructive pulmonary disease, who have severe airway hyperresponsiveness despite maintenance treatment with inhaled corticosteroids.
Effects of ranitidine treatment on patients with asthma and a history of gastro-oesophageal reflux: a double blind crossover study.
Forty eight patients with moderate to severe asthma were enrolled in a double blind crossover study designed to evaluate the effects of ranitidine treatment, 150 mg twice daily for four weeks, on gastro-oesophageal reflux, asthma control, and bronchial reactivity. All 48 had a history of reflux symptoms and 27 had in addition reflux associated respiratory symptoms. Thirty two patients had objective evidence of acid reflux on 24 hour pH monitoring (pH of less than 4 for more than 1% of the 24 hours) and 27 patients had a positive result in the acid perfusion test. Reflux symptoms were significantly improved after ranitidine treatment. Ranitidine treatment was associated with modest improvements in nocturnal asthma and daily use of inhaled bronchodilator drugs but there was no significant change in bronchial reactivity, lung function, peak flow, or the number of eosinophils in the blood. Comparisons between the effect of ranitidine treatment on asthma control were performed between patients with and without a history of reflux associated respiratory symptoms, with and without a positive result in the acid perfusion test, and with and without objective evidence of gastro-oesophageal reflux. A history of reflux associated respiratory symptoms was the only factor that predicted an improvement in asthma control after ranitidine treatment. These results indicate that antireflux treatment will produce only small improvements in asthma control in asthmatic patients with a history of gastro-oesophageal reflux.
Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study.
Eleven adult patients with nocturnal asthma, and gastro-oesophageal reflux documented by endoscopy or ambulatory oesophageal pH monitoring completed a double-blind cross-over study (4 week treatment, one week run-in and cross-over periods) comparing the effects of omeprazole 20 mg daily and placebo on asthma control assessed by symptoms, peak expiratory flow rate and bronchodilator usage. Omeprazole treatment did not improve asthma symptoms during the day or night, or peak expiratory flow rate readings. There was no difference in bronchodilator inhaler usage during omeprazole therapy. Treatment of gastro-oesophageal reflux with omeprazole in patients with nocturnal asthma and gastro-oesophageal reflux does not improve asthma symptoms or peak expiratory flow rate. This suggests that gastro-oesophageal reflux does not exacerbate bronchoconstriction in nocturnal asthma.
Relationship between asthma and gastro-oesophageal reflux.
Twenty patients with bronchial asthma who also had gastro-oesophageal reflux were investigated. The severity of their reflux was graded using symptom score of heartburn and regurgitation and by the following investigations: barium swallow and meal, fibreoptic endoscopy and biopsy, manometry and pH monitoring of the distal oesophagus, and an acid infusion test. Full lung function studies were performed and patients were entered into a double-blind crossover study using cimetidine to control their reflux in order to assess beneficial effects with respect to their respiratory problems. Eighteen patients completed the study. Significant improvements were seen in reflux and night time asthmatic symptoms, both these indices being measured on a scoring system. Home monitoring of peak flow values showed a statistical improvement for th last peak flow reading of the day. Fourteen patients felt that their chest symptoms had significantly improved during the cimetidine period.
A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux.
In order to study the importance of gastro-oesophageal reflux (GOR) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind, cross-over, placebo-controlled trial over four weeks in 37 children and adolescents (mean age 14 yrs) with bronchial asthma. Ranitidine 300 mg, (150 mg if B.W. was less than 40 kg) was given as a single evening dose during four weeks. In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus. The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma, not related to reduction of GOR. A modest (30%) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR. There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux. Side-effects of ranitidine were negligible. Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR. Further confirmative trials with more potent inhibitors of gastric acid secretion are, however, warranted.
Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?
The aim of the study was to investigate which features predict favourable response to omeprazole therapy in asthmatics with gastro-oesophageal reflux (GER). The study population consisted of 52 outpatient asthmatics with GER who had completed an intervention where they were randomized to receive omeprazole 40 mg once a day or placebo for 8 weeks. After a 2-week washout period the patients were crossed over. Asthma symptoms were found to be relieved > or = 20% in 18 (35%) patients who were thus regarded as responders. A logistic regression analysis was performed in order to identify which features separate the responders from the non-responders. More responders were found among the patients whose body mass index (BMI) was higher (P = 0.02) or whose distal esophageal reflux was more severe [total time (%) pH < 4 (P = 0.01) or time (%) pH < 4 in upright position (P = 0.04)]. Adding other predictors to the total time (%) pH < 4, which was the most significant predictor for response in multi-variate analysis, did not further increase the prediction for favourable outcome. It is concluded that severe distal oesophageal reflux and obesity predict amelioration in asthma symptoms after 8-week omeprazole treatment in asthmatics with GER. Adding more than one predictor does not seem to further increase prediction for favourable asthma response.
Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole.
STUDY OBJECTIVES: To investigate the prevalence of gastroesophageal reflux (GER) among patients with asthma and to determine the effect of omeprazole on the outcome of asthma in patients with GER.
DESIGN: A double-blind, placebo-controlled crossover study.
SETTING: Asthmatic patients who attended the pulmonary outpatient clinic of Turku University Central Hospital, Finland.
PATIENTS: One hundred seven asthmatic patients.
INTERVENTIONS: The patients who were found to have GER in ambulatory esophageal pH monitoring were randomized to receive either omeprazole, 40 mg qd, or placebo for 8 weeks. After a 2-week washout period, the patients were crossed over to the other treatment. Spirometry was performed at baseline and immediately after both treatment periods. Peak expiratory values, use of sympathomimetics, and pulmonary and gastric symptoms were recorded daily in a diary.
RESULTS: Pathologic GER was found in 53% of the asthmatic patients. One third of these patients had no typical reflux symptoms. Daytime pulmonary symptoms did not improve significantly (p = 0.14), but a reduction in nighttime asthma symptoms (p = 0.04) was found during omeprazole treatment. In the patients with intrinsic asthma, there was a decline in [corrected] FEV(1) values (p = 0.049). Based on symptom scores, 35% of the patients were regarded as responders to 8-week omeprazole treatment. The reflux (time [percent] of pH < 4) was found to be more severe (p = 0. 002) in the responders.
CONCLUSIONS: There is a high prevalence of GER in the asthmatic population. This reflux is often clinically "silent." After an 8-week omeprazole treatment, there was a reduction in nocturnal asthma symptoms, whereas daytime asthma outcome did not improve. There seems to be a subgroup of asthma patients who benefit from excessive antireflux therapy.
Effect of conservative treatment of oesophageal dysfunction on bronchial asthma.
Sixty-two patients with both bronchial asthma and oesophageal dysfunction (OD) were randomized into an OD treatment group and a control group. Patients in the treatment group were given advice and medication for their OD. No changes were made in their existing asthma therapy. Patients in the control group were told that there was a suspicion of OD which should be rechecked in 2 months. After 2 months the patients of the treatment group reported alleviation of their oesophageal and bronchial symptoms significantly more frequently than patients of the control group. Fewer signs of OD were found after treatment than before. Lung function tests did not differ between the group treated for 2 months and the control group but there was a significant reduction in consumption of beta-adrenergic stimulating drugs in the treatment group compared with the control group. In conclusion, treatment of OD improves not only oesophageal symptoms but also respiratory symptoms in asthmatic patients. OD should therefore be looked for in patients with bronchial asthma and treated whenever found.
Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux.
Patients presenting to a chest clinic because of adult-onset wheezing with no history of allergy had a 90 percent prevalence of gastroesophageal reflux, even though reflux symptoms were mild or absent. Ninety patients were randomly assigned to receive cimetidine or an identical placebo or to undergo antireflux surgery. During a six-month period, all groups improved clinically; the cimetidine and surgical groups improved more than the placebo group. The intake of pulmonary medication decreased significantly in both cimetidine and surgical groups. Pulmonary function test results improved in the cimetidine- and surgically treated patients; improvement was not statistically significant. At long-term follow-up, the surgical group maintained clinical improvement and decreased pulmonary medication intake, whereas the placebo group worsened. We conclude that gastroesophageal reflux can play a significant role in some patients with nonallergic pulmonary disease and that its treatment can improve pulmonary symptoms and objective measurements of pulmonary function.
Omeprazole improves peak expiratory flow rate and quality of life in asthmatics with gastroesophageal reflux.
OBJECTIVE: The aim of this study was to determine if omeprazole improves pulmonary function and quality of life in asthmatics with gastroesophageal reflux.
METHODS: This was a double blind, randomized, placebo-controlled cross-over trial. After a 4-wk lead-in period, nine patients with documented asthma and gastroesophageal reflux, were prescribed either omeprazole 20 mg, daily or placebo for 8 wk and then crossed over to the alternate treatment. Outcome measurements included: forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR), and responses on the Asthma Quality of Life Questionnaire, a validated disease specific measure of functional status.
RESULTS: After omeprazole treatment, compared with placebo, patients had higher mean morning and evening PEFR, mean absolute difference (95% CI): morning: 37.8 L/min. (10.9-64.6), evening: 31.2 (3.2-59.2). Omeprazole treatment led to higher mean overall scores on the Asthma Quality of Life Questionnaire, and on the subdomains of activity limitation, symptoms, and emotions (p = 0.039, 0.049, 0.024, 0.040). A trend toward higher FEV1 (mean: 15.6% difference) with omeprazole failed to reach statistical significance (p > 0.2).
CONCLUSIONS: After taking omeprazole for 8 wk, asthmatics with GER have better PEFR and quality of life than after placebo.
Does omeprazole (Prilosec) improve respiratory function in asthmatics with gastroesophageal reflux? A double-blind, placebo-controlled crossover study.
Gastroesophageal reflux (GER) is common among patients with asthma, and it has been speculated that high GER may exacerbate asthma in some. This study was designed to determine if suppression of acid reflux in patients with asthma would improve pulmonary function. A double-blind, placebo-controlled crossover study design was used to determine the effect of GER suppression with omeprazole (20 mg twice daily) on pulmonary function among asthmatic patients with esophagitis. Four of 15 (27%) asthma patients with GER were shown to have a > or = 20% net improvement in pulmonary function (FEV1) after treatment for six weeks with omeprazole. These results indicate that some patients with asthma and GER will have improved pulmonary function when acid GER is treated with omeprazole.
Ambulatory pH monitoring of gastro-oesophageal reflux in "morning dipper" asthmatics.
A causal relation between gastro-oesophageal reflux and nocturnal asthma has been postulated. Forty four adult asthmatics underwent ambulatory monitoring of their oesophageal pH over 24 hours to find out if there was such a relation. Of these 21 showed significant "morning dipping" in which the peak expiratory flow falls during the night. Asthmatics with morning dipping had a history of nocturnal wheeze and a higher incidence of reflux symptoms, but measurement of oesophageal pH showed no significant difference in the amount or pattern of reflux when compared with "non-dippers." Overall, 15 asthmatics had gastro-oesophageal reflux, and these participated in a randomised, double blind crossover trial of ranitidine versus placebo. No significant difference was found in the peak expiratory flow rates or subjective evaluation of well being of the patients.
Adult asthma and gastro-oesophageal reflux: the effects of omeprazole therapy on asthma.
BACKGROUND: Approximately 40-60% of patients with asthma have gastro-oesophageal reflux (GOR) and it has been postulated that this may worsen asthma severity.
AIMS: To investigate the effect of the potent gastric acid inhibitor omeprazole 40 mg orally daily on peak expiratory flow rate (PEFR), asthma symptoms and histamine bronchial responsiveness in adult patients with both asthma and GOR.
METHODS: This was a double blind, randomised, placebo controlled, crossover study. Upper gastrointestinal endoscopy, 24 hour oesophageal pH measurements, spirometry and histamine bronchoprovocation test (HIT) were performed prior to entry. Phase 1:2 week placebo run-in period, with baseline recording of PEFR, asthma and GOR symptoms, and use of inhaled beta 2-agonist. Phase 2: patients randomised to receive either placebo or omeprazole 40 mg/d for four weeks. Phase 3: placebo for two weeks. Phase 4: patients crossed over to opposite treatment from that of phase 2. Spirometry, and diary cards were assessed at beginning and end of phases 2 and 4. HIT was performed at the end of phase 2 and at the beginning and end of phase 4.
RESULTS: Twenty patients (eight female and 12 male) completed the study. The evening but not morning PEFR (% predicted) were significantly higher on omeprazole vs placebo (82 +/- 4% SEM vs 79 +/- 4% SEM; p < 0.05). No significant differences were found in FEV1, FVC, histamine bronchial responsiveness and diurnal variation of PEFR between placebo and omeprazole treatments. Similarly, there were no significant differences during placebo and omeprazole periods in day time wheeze, cough, breathlessness, beta 2-agonist use or night time wheeze and breathlessness. Day and night heartburn symptoms were significantly better on omeprazole vs placebo (p < 0.05).
CONCLUSIONS: Omeprazole 40 mg daily improved evening PEFR in asthma patients with GOR. However, asthma symptoms, inhaled beta 2-agonist use and histamine bronchial responsiveness did not change.
Options:
A: Treatments for gastro-oesophageal reflux consistently improved lung function, asthma symptoms, nocturnal asthma, and the use of asthma medications.
B: There was no overall improvement in asthma following treatment for gastro-oesophageal reflux, although some subgroups of patients may benefit.
C: All patients with both asthma and gastro-oesophageal reflux showed significant improvement in asthma symptoms after receiving anti-reflux treatment.
D: Anti-reflux treatments were found to be harmful and worsened asthma symptoms in most patients.
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B
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91
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the effectiveness of different doses of systemic corticosteroids in the management of acute severe asthma in hospitalised patients? Please answer this question based on the information provided below:
Corticosteroids in acute severe asthma: effectiveness of low doses.
BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.
METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.
RESULTS: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.
CONCLUSIONS: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.
Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.
Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.
Need for intravenous hydrocortisone in addition to oral prednisolone in patients admitted to hospital with severe asthma without ventilatory failure.
52 severely ill asthmatic patients requiring acute admission to hospital entered a double-blind placebo-controlled trial to determine whether intravenous hydrocortisone given in addition to high-dose oral prednisolone and standard bronchodilator therapy accelerated recovery. Patients who had been given parenteral steroids before admission, by comparison with those who had not received such treatment, had been deteriorating for a shorter period before admission, had received more injected or nebulised bronchodilator therapy, and had higher admission peak flows. As judged by peak flow measurements 24 h after admission, parenteral steroids had no effect on the outcome, irrespective of whether they were given before or after (ie, intravenous hydrocortisone) admission. There is no evidence for the continued use of intravenous hydrocortisone in addition to oral prednisolone and bronchodilator therapy in patients admitted to hospital with severe asthma without ventilatory failure.
A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus.
Twenty-five consecutive patients admitted with status asthmaticus were blindly randomized to receive intravenous (IV) methylprednisolone every six hours for three days at one of the following dosages: (1) low, 15 mg; (2) medium, 40 mg; or (3) high, 125 mg. All other therapy, including IV and inhaled bronchodilators, was kept constant. We measured forced expiratory volume in 1 s (FEV1) to quantitate response. The high-dose group improved significantly by the end of the first day, the medium-dose group improved by the middle of the second day, but the low-dose group did not improve significantly in three days. Together, the high- and medium-dose groups were significantly improved (FEV1 greater than 50% of predicted) compared with the low-dose group. No serious steroid side effects were encountered. We conclude that the greater benefit of higher doses of steroids, such as 125 mg of methylprednisolone every six hours, justifies their use in severe asthma.
High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma.
The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma.
Controlled trial of intravenous corticosteroids in severe acute asthma.
BACKGROUND: The value of corticosteroids in severe acute asthma continues to be debated.
METHODS: Ninety consecutive patients admitted to the emergency room with severe acute asthma were studied in a randomised, double blind, controlled trial to determine the efficacy of corticosteroids. Eighty two patients completed the study. All received oxygen therapy and intensive bronchodilator treatment. The patients were divided into three groups for steroid treatment, receiving intravenous methylprednisolone 10 mg/kg every four hours for 48 hours (29 patients, group A); intravenous methylprednisolone 2 mg/kg every 4 hours for 48 hours (27 patients, group B); or no intravenous corticosteroids (26 patients, group C).
RESULTS: There were no differences on admission among the three groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), or arterial oxygen or carbon dioxide tension; and the rates of recovery in FEV1, FVC, and PEF were similar.
CONCLUSIONS: Corticosteroids given with bronchodilators have not shown a beneficial effect in the first 48 hours of recovery of severe acute asthma. Only in those patients who failed to respond by the third hour of treatment, and in those who were previously taking oral corticosteroids, does a favourable, though not statistically significant, effect appear to occur.
Methylprednisolone pulse therapy in severe acute asthma.
In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance.
Are intravenous corticosteroids required in status asthmaticus?
Seventy-seven patients with status asthmaticus were prospectively studied to compare oral with intravenous methylprednisolone. Patients were given methylprednisolone, either 160 or 320 mg orally or 500 or 1000 mg intravenously, daily in equally divided doses. They were randomly assigned to either group on a daily sequential basis. Spirometry was performed within one hour of the initial dose of steroids. The mean presenting forced expiratory volume in 1 s was 26% of the predicted value. Spirometry was then repeated every six hours for the first 24 hours and then every eight to 12 hours until discharge or 72 hours, whichever occurred first. There were no significant differences in the incidence of respiratory failure, forced expiratory volume in 1 s, days of hospitalization, rate of improvement in pulmonary function, or side effects. No patient who went into respiratory failure did so more than three hours after receiving the initial dose of steroids. We conclude that oral methylprednisolone is safe and effective in the treatment of status asthmaticus.
Intravenous methylprednisolone in adults in status asthmaticus. Comparison of two dosages.
Options:
A: Higher doses of corticosteroids are significantly more effective than lower doses in improving pulmonary function.
B: Lower doses of corticosteroids are significantly more effective than higher doses in improving pulmonary function.
C: There are no significant differences in effectiveness between higher and lower doses of corticosteroids in improving pulmonary function.
D: Higher doses of corticosteroids are associated with significantly fewer side effects compared to lower doses.
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C
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92
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What conclusion can be drawn about the use of nicotine as a treatment for Alzheimer's disease based on the available evidence? Please answer this question based on the information provided below:
Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease.
RATIONALE: Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects.
OBJECTIVE: The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer's disease subjects over a 4-week period.
METHODS: The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol) for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and 3 and 5 mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy.
RESULTS: Nicotine significantly improved attentional performance as measured by the Conners' continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function.
CONCLUSIONS: The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer's disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.
Options:
A: Nicotine is a reliable and effective treatment for Alzheimer's disease.
B: Nicotine has been proven to significantly improve memory and cognitive function in Alzheimer's patients.
C: There is no reliable evidence to support the use of nicotine as a treatment for Alzheimer's disease.
D: Nicotine is harmful and should not be used in Alzheimer's disease treatment.
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C
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93
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What are the effects of routine prophylactic drugs given with snake antivenom to prevent adverse reactions? Please answer this question based on the information provided below:
Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites.
OBJECTIVE: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom.
DESIGN: Sequential randomised, double blind, placebo controlled trial.
SETTING: Public hospital in a venom research institute, São Paulo, Brazil.
PARTICIPANTS: 101 patients requiring antivenom treatment after being bitten by bothrops snakes.
INTERVENTION: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom.
MAIN OUTCOME MEASURES: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom.
RESULTS: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo.
CONCLUSION: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.
Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial.
OBJECTIVE: To assess the efficacy and safety of low dose adrenaline injected subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum in patients admitted to hospital after snake bite.
DESIGN: Prospective, double blind, randomised, placebo controlled trial.
SETTING: District general hospital in Sri Lanka.
SUBJECTS: 105 patients with signs of envenomation after snake bite, randomised to receive either adrenaline (cases) or placebo (controls) immediately before infusion of antivenom serum.
INTERVENTIONS: Adrenaline 0.25 ml (1:1000).
MAIN OUTCOME MEASURES: Development of acute adverse reactions to serum and side effects attributable to adrenaline.
RESULTS: 56 patients (cases) received adrenaline and 49 (controls) received placebo as pretreatment. Six (11%) adrenaline patients and 21 (43%) control patients developed acute adverse reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse reactions to serum were also seen in the adrenaline patients for each category of mild, moderate, and severe reactions. There were no significant adverse effects attributable to adrenaline.
CONCLUSIONS: Use of 0.25 ml of 1:1000 adrenaline given subcutaneously immediately before administration of antivenom serum to patients with envenomation after snake bite reduces the incidence of acute adverse reactions to serum.
Options:
A: Routine prophylactic adrenaline reduces adverse reactions to antivenom, while antihistamines show no benefit.
B: Routine prophylactic antihistamines reduce adverse reactions to antivenom, while adrenaline shows no benefit.
C: Both routine prophylactic adrenaline and antihistamines reduce adverse reactions to antivenom.
D: Neither routine prophylactic adrenaline nor antihistamines reduce adverse reactions to antivenom.
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A
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94
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What was the conclusion regarding the effectiveness of inhaled steroids compared to oral prednisolone for adults with chronic asthma? Please answer this question based on the information provided below:
Comparison of inhaled beclomethasone dipropionate 1000 micrograms twice daily and oral prednisone 10 mg once daily in asthmatic patients.
BACKGROUND: Glucocorticosteroids are widely used as drugs of first choice in the treatment of moderate to severe asthma. The effects of inhaled steroids in high doses have been compared with oral prednisone in asthmatic patients in a double blind crossover study.
METHODS: The trial consisted of a two week run in period followed by two four week treatment periods separated by a four week washout. During the treatment period patients took either 1000 micrograms beclomethasone dipropionate twice daily and placebo tablets once daily, or 10 mg prednisone daily in one morning dose and placebo inhaler twice daily. The effects of treatment on the provocative dose of histamine producing a 20% fall in FEV1 (PC20 histamine), peak flow measurements at home, and spirometric measurements in the clinic, as well as on the basal and stimulated plasma cortisol levels were measured.
RESULTS: Seventeen patients with asthma completed the study. After four weeks of treatment beclomethasone dipropionate showed a significantly better effect on morning peak expiratory flow rate than prednisone. There was a trend to a greater improvement in the PC20 histamine in patients receiving beclomethasone dipropionate than in those receiving prednisone. There were no significant differences in spirometric values, symptom scores, or basal and stimulated cortisol levels between the treatments. The within treatment analysis showed a significant effect of prednisone on stimulated cortisol levels but not of beclomethasone dipropionate.
CONCLUSIONS: Beclomethasone dipropionate 1000 micrograms twice daily has a slightly greater therapeutic effect in this population of asthmatic patients than 10 mg of prednisone once a day with less effect on adrenocortical function.
Inhaled corticosteroids compared with oral prednisone in patients starting long-term corticosteroid therapy for asthma. A controlled trial by the British Thoracic and Tuberculosis Association.
Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.
A double-blind comparison of beclomethasone dipropionate aerosol and prednisolone in asthmatic patients.
Effect of prednisone and beclomethasone dipropionate on airway responsiveness in asthma: a comparative study.
To examine the effect of corticosteroids on bronchial hyperresponsiveness, a randomised, double dummy, single blind crossover study was performed in 18 subjects with chronic asthma, comparing the effect of three weeks' treatment with inhaled beclomethasone dipropionate, 1200 micrograms daily, and oral prednisone 12.5 mg daily. The 12 week study began with a three week run in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a three week washout period. Patients kept daily Airflometer readings and attended the laboratory every three weeks for spirometry and a histamine inhalation test for determining the provocative dose of histamine causing a 20% fall in FEV1 (PD20). The mean FEV1 at the start was 1.9 litres (56% predicted). There was no significant change in PD20 with prednisone treatment, the mean PD20 being 0.56 and 0.59 mumol before and after treatment. There was, however, a significant improvement in PD20 with beclomethasone dipropionate treatment, the geometric mean PD20 being 0.38 and 1.01 mumol before and after treatment (p less than 0.001). There was a small but significant improvement in mean FEV1 after beclomethasone dipropionate treatment--from 1.9 to 2.2 litres--but no change after prednisone. Both medications produced significant and similar improvements in morning and evening Airflometer readings, post-bronchodilator improvement, and diurnal variation. Thus at doses that had similar beneficial effects on lung function beclomethasone dipropionate caused a significant improvement in bronchial hyperresponsiveness whereas prednisone caused no change. The superior topical anti-inflammatory effect of beclomethasone dipropionate may account for the different effects on bronchial hyperresponsiveness.
A comparative study of the efficacy of inhaled beclomethasone and systemic prednisolone in bronchial asthma.
Comparison of beclomethasone dipropionate aerosol and prednisolone in reversible airways obstruction.
This paper describes a double-bond crossover trial of prednisolone and beclomethasone dipropionate aerosol in 38 steroid-dependent patients with reversible diffuse airways obstruction. Altogether there was no difference in the patient's preference of the two treatment groups or in the number of times they used their bronchodilator aerosol, or in the forced expiratory volume in one second, vital capacity, or peak expiratory flow rate in the two treatment groups. The plasma cortisol levels when the patients were on the aerosol were much higher than when they were on prednisolone. The use of inhaled aerosol steroids seems to be preferable as it eliminates the usual complications of oral steroid therapy.
Comparison of inhaled budesonide with oral prednisolone at two dose-levels commonly used for the treatment of moderate asthma.
The purpose of the study was to compare the anti-asthmatic efficacy of two doses of inhaled budesonide with two doses of oral prednisolone commonly used in clinical practice. The patients studied had not been taking regular inhaled glucocorticosteroids and so there was minimal interference from previous medication. The study was conducted as two double-blind crossovers with a washout period between them - firstly, comparing 400 micrograms budesonide with 5 mg prednisolone per day and secondly, 800 micrograms budesonide with 10 mg prednisolone per day. Lung function and symptoms were improved significantly from run-in by all treatments and improvement on both drugs was dose-dependent. When low-dose treatments were compared, mean morning peak expiratory flow rate was higher during budesonide treatment and, as a result, diurnal variation was significantly less than that during prednisolone treatment. At the higher doses, differences between the drugs were not observed, but this may have been due to the fact that a "ceiling effect" had been reached.
Comparison between inhaled and oral corticosteroids in patients with chronic asthma.
Corticosteroid inhalants, beclomethasone dipropionate (BDP) and budesonide, were compared with each other and with oral prednisolone in patients with steroid dependent chronic bronchial asthma. In a first study in 23 patients the PEF values during 2 weeks' therapy with a supplementary dose of 200 or 800 micrograms of budesonide or 400 micrograms of BDP were found to be better than those noted during a preceding week with a supplementary dose of 30 mg prednisolone. In a following open study 31 patients on an initial maintenance therapy consisting of a standard dose of BDP and a mean daily dose of 9 mg prednisolone were treated with increasing (when necessary) doses of budesonide instead of BDP and decreasing (if possible) dose of prednisolone. After one year's treatment 21 patients were well controlled without oral prednisolone, and the mean prednisolone dose for the entire group was 2.5 mg a day. During the study lung function significantly improved in the subgroup of patients who were initially on the highest dose of oral prednisolone. In a third study in 17 patients the effects on lung function and on symptom scores were compared after a supplementary therapy with 10 or 20 mg oral prednisolone, or 400 or 800 micrograms budesonide. During such treatment the effect of 400 micrograms budesonide on PEF was the same as that of 10 mg prednisolone, and 800 micrograms budesonide and 20 mg prednisolone seemed to be equipotent. For corticosteroid dependent patients with severe asthma the introduction of budesonide seems to offer an improvement, allowing substantial reduction or withdrawal of oral prednisolone. This had not been possible earlier in such patients without deterioration of lung function and their clinical state. During treatment with budesonide lung function remained unchanged or improved.
Efficiency of inhaled versus oral steroid treatment of chronic asthma.
The therapeutic efficiency of oral vs. inhaled steroid treatment for chronic asthma was compared in several graded-dose, double-blind controlled trials. Inhaled steroid proved significantly more effective than alternate-morning prednisone when the two regimens were compared in the same patients at equivalent levels of systemic glucocorticoid activity. Furthermore, if given in sufficient dosage, inhaled steroids proved equally as effective as oral prednisone given daily, and better tolerated than the latter. The data support a broadening of the therapeutic role of inhaled steroid drugs to include higher dosages and patients with more severe grades of asthma. To facilitate this, concentrated formulations are needed. Until the latter become available to the practitioner, combinations of inhaled plus oral steroid treatment may be used, since these have been shown to improve the efficacy of chronic steroid therapy without worsening its adverse effects.
Bioequivalent doses of budesonide and prednisone in moderate and severe asthma.
We determined the relative antiasthmatic and systemic glucocorticoid potencies of inhaled budesonide (BUD) versus morning-dose oral prednisone (PRED) in 34 adult patients with asthma over a dose range extending from conventional to high and potentially toxic levels, 3.2 mg of BUD or 40 mg of PRED per day. Changes in symptom frequency and severity, FEV1, and peak expiratory flow rate were measured during a double-blind, double-dummy controlled, crossover protocol. The drugs proved equally effective, provided a sufficient dosage was administered. The dose required to eliminate recurrently disabling asthma relapses in these patients was about 2.0 mg of BUD per day or greater than 40 mg of PRED per day. On the average, BUD doses greater than or equal to 1.84 mg/day/70 kg adult (26.3 micrograms/kg/day) exhibited systemic effects on the 8 AM serum cortisol level and blood eosinophil count equivalent to greater than or equal to 15 mg of PRED per day. The latter doses are known to be associated with steroid-induced complications, such as osteoporosis. However, the level of systemic glucocorticoid activity produced by any particular dose of BUD in these patients was consistently much lower than that produced by the dose of PRED needed to achieve an equivalent level of antiasthmatic response. Thus, the use of high-dose inhaled BUD appears clinically reasonable and ethically acceptable in patients with severe asthma in whom the alternative is their continuing dependency on PRED.
Options:
A: Inhaled steroids at all doses were less effective than oral prednisolone.
B: Inhaled steroids at doses of 300-2000 mcg/day were as effective as oral prednisolone at doses of 7.5-12 mg/day.
C: Oral prednisolone at doses of 5 mg/day was more effective than inhaled steroids at doses of 300-400 mcg/day.
D: Inhaled steroids were only effective at doses higher than 2000 mcg/day.
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B
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95
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What is the effect of administering systemic corticosteroids within one hour of presentation to the emergency department on hospital admission rates for patients with acute asthma? Please answer this question based on the information provided below:
Prednisolone and salbutamol in the hospital treatment of acute asthma.
The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.
Prednisolone and salbutamol in the hospital treatment of acute asthma.
The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.
Early parenteral corticosteroid administration in acute asthma.
To test the hypothesis that early parenteral corticosteroid administration may be associated with a rapid improvement in airflow obstruction in adult asthmatic patients, a randomized, double-blind placebo-controlled study was carried out. Forty-five adult asthmatic patients, with initial peak expiratory flow rates (PEFRs) of < 200 L/sec received an intravenous bolus of either 125 mg methylprednisolone (MP) or normal saline before any other emergency department treatments. This was immediately followed by 3 aerosol treatments of 2.5 mg of albuterol separated by 20-minute intervals. PEFRs and heart rates were measured over a 1-hour time frame. There was not a significantly higher rate of increase of PEFR in the MP group compared with the saline group. Similarly, the rate of increase in percent PEFR showed a trend to being higher in the saline group (P = .061). There was no significant difference in the proportion of hospitalizations and side effects between the two groups. Adjustment for other variables did not result in a model showing an enhanced PEFR improvement with MP treatment. This study does not support the concept that corticosteroid treatment effects are beneficial within the first hour after administration. Further studies of rapid-acting modalities to enhance bronchodilation are needed in treating acute asthmatics.
Rapid improvement of peak flow in asthmatic patients treated with parenteral methylprednisolone in the emergency department: A randomized controlled study.
STUDY OBJECTIVE: Corticosteroids are thought to exert their physiologic effects in asthma over the course of several hours. In this study we tested the hypothesis that intravenous methylprednisolone improves airflow in a shorter time frame (2 hours) in adults with acute asthma.
METHODS: In a randomized, double-blind, placebo-controlled trial, 56 adult asthmatic patients with peak expiratory flow rates (PEFRs) less than 50% predicted after an initial albuterol aerosol treatment were studied. These patients were randomly assigned to treatment with either 125 mg of intravenous methylprednisolone or an equivalent volume of normal saline solution (placebo). Patients were also treated with identical schedules of nebulized ipratropium and albuterol. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time. PEFRs were assessed at baseline and at 1 and 2 hours. Heart rate changes over time and the proportion of admissions in the 2 groups were also compared.
RESULTS: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the methylprednisolone treatment group (P =. 002 and P =.005, respectively). The increases in geometric mean peak flow at 60 and 120 minutes were 79 and 96 L/min for the methylprednisolone group and 54 and 68 L/min for the placebo group. There was also a significantly different change in heart rates with time between the methylprednisolone and placebo groups (P =.029), with the placebo group showing a moderate increase in heart rate over time. Although the proportion of patients admitted for status asthmaticus was less in the methylprednisolone treatment group (8/30) compared with the placebo group (10/26), this difference in proportions (-.118, 95% confidence interval -.363 to.127) was not significant.
CONCLUSION: These data suggest that use of corticosteroids should be considered relatively early in the treatment of patients with acute asthma in whom initial bronchodilator therapy fails to produce an adequate response.
A controlled trial of methylprednisolone in the emergency treatment of acute asthma.
Ninety-seven acutely ill patients with bronchial asthma were enrolled in a double-blind, placebo-controlled, randomized trial of intravenous methylprednisolone (125 mg), given on presentation in the emergency room in addition to standard emergency treatments for asthma. Subjective and spirometric indexes of the severity of the asthma were similar on entry into the study in all patients, but only 9 of 48 patients (19 percent) treated with methylprednisolone required hospital admission, as compared with 23 of 49 patients (47 percent) in the control group (P less than 0.003). Our results suggest that prompt use of glucocorticoids in the emergency treatment of severe asthma can prevent significant morbidity, reduce the number of hospitalizations, and effect substantial savings in health care costs.
A controlled study of the effects of single doses of hydrocortisone on the resolution of acute attacks of asthma.
To evaluate the effects of corticosteroids on the resolution of acute attacks of asthma, 38 young, acutely ill, asthmatic subjects were given a single intravenous injection of either 0.25, 0.50 or 1.0 g of hydrocortisone hemisuccinate or a placebo (sterile saline solution) in a random, double blind manner. Each was then treated with isoproterenol, at hourly intervals, for a minimum of six hours, and the serial changes in plethysmography, spirometry, lung volumes, subjective complaints and physical findings that occurred as the patients improved were observed. No statistical differences were found in any of the physiologic or clinical variables between those patients given any dose of steroids and their matched controls. From this it has been concluded that hydrocortisone, in the doses and route of administration employed, does not produce any immediate benefits in the treatment of acute asthma.
Early administration of hydrocortisone in the emergency room treatment of acute asthma: a controlled clinical trial.
STUDY OBJECTIVE: To determine whether early administration of a single dose of intravenous hydrocortisone (500 mg) modified the need for hospitalization and duration of treatment, and improve pulmonary function assessed by subjective and objective criteria of acute asthma patients.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: The emergency room (ER) of a large, urban hospital with primary and referral care responsibilities.
PATIENTS: Ninety-eight patients from 18 to 50 years of age with acute bronchial asthma, with a PEFR and FEV1 in the first second below 50% of predicted value (FEV1 mean % of predicted = 27.8 +/- 10.0) and without history of chronic cough or other medical disease.
INTERVENTIONS: The corticosteroid group received 500 mg of intravenous hydrocortisone whereas the control group received intravenous normal saline immediately after arrival to the ER. Additional treatment included salbutamol delivered with metered-dose inhaler into a spacer device (Volumatic), in four puffs actuated in rapid succession (100 micrograms per actuation), at 10-min intervals. The final mean dose was 5.7 mg for the steroid group and 5.6 mg for the control one (P = 0.86). Hospitalization was mandatory if total treatment time was greater than 6 h.
MEASUREMENTS AND RESULTS: Age, sex, PEFR, FEV1, FVC, symptom index, and corticosteroids use were similar in both groups. FEV1 expressed as mean % of predicted was 54.6 +/- 17.3% in the control group and 54.6 +/- 17.4% in the steroid group (P = 0.75). Duration of ER treatment was 2.22 +/- 1.75 h in the corticosteroid group and 2.24 +/- 1.70 h in the control group (P = 0.81). The hospital admission rate was 10.2% for the corticosteroid group and 8.16% for the control group. There were no differences between the groups when patients admitted or discharged were examined separately.
CONCLUSIONS: Early administration of corticosteroids does not modify outcome of ER treatment of asthma, and does not improve pulmonary function in the first 6 h of treatment. In accord with this, administration of corticosteroids to these patients could be delayed by several hours without modifying clinical outcome. When an aggressive beta-agonist bronchodilator regimen is used, it obviates the need for steroids in this early stage of treatment.
Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma.
BACKGROUND: Recent studies have shown that the use of parenteral corticosteroids in the emergency department decreases the hospitalization rate for patients with acute asthma. We studied the efficacy of oral corticosteroids in the emergency department treatment of moderately ill children with acute asthma.
METHODS: Emergency department patients aged 1 through 17 years whose chief complaint was acute asthma were assigned a pulmonary index, based on clinical evaluation. Those with a moderate exacerbation (pulmonary index = 9 through 13) received either 2 mg/kg of oral prednisone or placebo in a randomized, double-blind fashion. Patients in each group were then treated with an identical regimen of frequent aerosolized albuterol, for up to a maximum of 4 hours.
RESULTS: Seventy-five patients were assessed. Overall, 11 (31%) of 36 in the prednisone group required hospitalization compared with 19 (49%) of 39 in the placebo group (P = .10). Among the sickest patients (initial pulmonary index > 10), 7 (32%) of 22 prednisone-treated patients required hospitalization compared with 13 (72%) of 18 placebo-treated patients (P < .05). Among patients who had a suboptimal response to initial beta 2-agonist therapy and who therefore would have been hospitalized had treatment been restricted to 2 hours, 9 (45%) of 20 in the prednisone group ultimately required hospitalization when duration of care was extended 2 additional hours compared with 15 (83%) of 18 in the placebo group (P < .05). In addition, prednisone-treated patients had a significantly greater improvement in median pulmonary index (5.0 vs 3.0, P < .001).
CONCLUSIONS: These data demonstrate that oral prednisone, within 4 hours of its administration, reduced the need for hospitalization among a subset of children treated in the emergency department for acute asthma.
High-dose methylprednisolone as initial therapy in patients with acute bronchospasm.
The use of steroids in treating acute respiratory obstruction is still controversial. In this double-blind controlled trial, we decided to examine the beneficial effects of a single large dose of methylprednisolone (MSSP), using objective criteria. In the emergency setting, methylprednisolone (30 mg/kg) has been shown to decrease the need for hospital admission in patients with acute bronchospasm. No difference in this improvement was seen among patients in the steroid-dependent or non-steroid-dependent populations. Based on our findings, we suggest that the early use of single-dose steroid therapy is appropriate treatment for patients with acute bronchospastic attacks.
Early administration of corticosteroids in emergency room treatment of acute asthma.
STUDY OBJECTIVE: To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: The emergency room of a large, urban hospital with primary and referral care responsibilities.
PATIENTS: Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups.
INTERVENTIONS: The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours.
MEASUREMENTS AND MAIN RESULTS: Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group.
CONCLUSIONS: These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted.
Effect of a single oral dose of prednisolone in acute childhood asthma.
140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care.
Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial.
A controlled double-blind trial was carried out to assess the effect of the early introduction of combined corticosteroid and beta-adrenergic drugs for the treatment of acute asthma in infants and toddlers. Seventy-four emergency room patients (aged 7 to 54 months) who were treated for acute asthma were studied. Treatment included, in addition to salbutamol inhalations, a single dose of intramuscular methylprednisolone (4 mg/kg) or normal saline as placebo. The patients were reevaluated 3 hours after initiation of treatment. At that time, patients were either admitted or discharged based on a clinical decision. Only 8 (20%) of 39 patients treated with steroids were admitted, compared with 15 (43%) of 35 in the placebo group (P less than .05). Sequential analysis of 33 pairs, matched by age and severity of symptoms, revealed statistically significant reduced admission rates in patients treated with steroids. In the younger patients (6 to 24 months), admission rate was significantly lower for those treated with steroids (18%) as compared with those treated without steroids (50%) (P less than .05). In the older group (24 to 54 months), the trend was similar but not statistically significant: 23% vs 31% in the steroid and placebo groups, respectively. These data indicate that corticosteroid treatment combined with an adrenergic agent, given early during an acute asthmatic episode, significantly reduces the hospital admission rate of infants and toddlers.
A controlled trial of methylprednisolone in the early emergency department treatment of acute asthma in children.
Asthma continues to be a leading cause for pediatric hospitalizations. A study using high-dose intravenous (i.v.) steroids early in the emergency department (ED) care of adults with acute asthma reported a 60% reduction in hospitalization rate. Limited data are available for children. We hypothesized that the addition of early administration of high-dose methylprednisolone (MP) in routine ED care of asthmatic children would reduce the need for hospitalization by 50%. Eighty-eight children with asthma, aged four to 18 years, were enrolled into a prospective, randomized, double-blind, placebo-controlled study of MP given within 45 (mean 23) minutes of arrival to the ED. After initial evaluation, children received either 2 mg/kg of MP IV or an equivalent amount of placebo (P). Patients then received the usual ED management of their acute exacerbation. Groups were similar in age, sex, and severity of illness (by asthma scoring, respiratory rate, and peak flow). ED treatment (number of aerosols and the use of theophylline) was similar for both groups. The mean time to disposition was 2.9 hours. Sixty-four percent of the children were discharged from the ED. No significant differences were found between the admission rates of the MP and P groups (41% MP vs 33% P, P = 0.44, chi 2, 95% CI for decrease in MP vs P groups -28 to +12%). The average hospital stay was shorter for those children treated with MP (79 hours vs 90 hours). We conclude that IV methylprednisolone given as an adjunct to routine ED care of children with acute asthma is unlikely to markedly reduce hospitalization rates.
Options:
A: It significantly reduces hospital admission rates, especially in patients with more severe asthma and those not currently receiving steroids.
B: It has no significant effect on hospital admission rates.
C: It increases hospital admission rates due to side effects.
D: It only reduces hospital admission rates in adults, not in children.
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A
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96
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What is the effectiveness of single session psychological debriefing in managing psychological distress and preventing post traumatic stress disorder (PTSD) in individuals recently exposed to a traumatic event? Please answer this question based on the information provided below:
Randomised controlled trial of psychological debriefing for victims of acute burn trauma.
BACKGROUND: Psychological debriefing (PD) is widely used following major traumatic events in an attempt to reduce psychological sequelae.
METHOD: One hundred and thirty-three adult burn trauma victims entered the study. After initial questionnaire completion, participants were randomly allocated to an individual/couple PD group or a control group who received no intervention; 110 (83%) were interviewed by an assessor blind to PD status three and 13 months later.
RESULTS: Sixteen (26%) of the PD group had PTSD at 13-month follow-up, compared with four (9%) of the control group. The PD group had higher initial questionnaire scores and more severe dimensions of burn trauma than the control group, both of which were associated with a poorer outcome.
CONCLUSION: This study seriously questions the wisdom of advocating one-off interventions post-trauma, and should stimulate research into more effective initiatives.
An experimental evaluation of crisis intervention.
Crisis intervention: an experimental study of the effects of a brief period of counselling on the anxiety of relatives of seriously injured or ill hospital patients.
This study was designed to examine the effects of anxiety levels, as measured by the Gottschalk & Gleser (1969) and the Viney & Westbrook (1976) content analysis scales, of a brief period of supportive counselling of relatives who arrived at a hospital emergency admitting ward with a seriously ill or injured patient. Verbal samples were taken for analysis from the subjects before and after a period of counselling (or a period of no counselling for the control group). The results showed that the initial anxiety levels for subjects in both groups was very high. For both the psychoanalytically oriented Gottschalk & Gleser anxiety scale and the Viney & Westbrook scale of cognitive anxiety there was a decrease in the level of anxiety for the counselled group compared with the non-counselled group. The results showed that such crisis intervention in hospitals for relatives who accompany patients to the hospital can reduce their very high levels of diffuse and generalized anxiety.
Effect of timing of critical incident stress debriefing (CISD) on posttraumatic symptoms.
Seventy-seven civilian employees who were victims of robbery were randomly assigned to either an immediate (< 10 hr) or delayed (> 48 hr) debriefing group, using the J. Mitchell (1983) CISD protocol. Scores on the Posttraumatic Stress Diagnostic Scale were obtained at 4 time intervals: debrief, 2 and 4 days post-debrief, and 2 weeks postrobbery. The number and severity of symptoms did not differ at debrief, but were lower for the immediate than for the delayed group at each subsequent time interval. The number and severity of symptoms declined across time intervals; however, although this reduction was pronounced for the immediate group it was minimal for the delayed group. The results supported use of immediate debriefing with this type of incident and victim.
PTSD in ambulant RTA victims: a randomized controlled trial of debriefing.
This report examines initial distress levels, course of symptoms, incidence of posttraumatic stress disorder (PTSD), predictors of short-term outcome, and value of prophylactic counseling in a consecutive series of 40 ambulant trauma clinic attenders with minor road traffic accident (RTA) injuries. Subjects were randomly allocated to intervention and monitoring groups following assessment at a mean of 7 days posttrauma and reassessed at 3 months using a variety of standard rating scales. Seventy-five percent reported significant levels of distress at 1 week posttrauma. By 3 months this had decreased sharply to 35%, and 22% were significantly impaired by clinical assessment. Incidence of PTSD over 3 months was estimated at 19% and point prevalence at 3 months posttrauma was 9%. High initial distress, increasing age, and high levels of perceived threat were significant independent predictors of morbidity, and no significant differences in outcome were found between intervention and monitoring groups at 3 months.
A randomised controlled trial of psychological debriefing for victims of road traffic accidents.
Can midwives reduce postpartum psychological morbidity? A randomized trial.
BACKGROUND: Women who are traumatized after childbirth find that listening, support, counseling, understanding, and explanation are the most useful treatments. However, little evidence is available from randomized trials of the relative efficacy of these treatments as a positive postnatal intervention. This study purpose was to examine if postnatal "debriefing" by midwives can reduce psychological morbidity after childbirth.
METHOD: A randomized trial was conducted in a regional teaching hospital in northwest England. One hundred and twenty postnatal primigravidas were allocated by sealed envelopes to receive the debriefing intervention (n = 56) or not (n = 58). The main outcome measure was the Hospital Anxiety and Depression (HAD) scale administered by postal questionnaire 3 weeks after delivery. The proportion of women in each group with anxiety and depression scores of more than 10 points were compared, using odds ratios and 95% confidence intervals.
RESULTS: Women who received the intervention were less likely to have high anxiety and depression scores after delivery when compared with the control group.
CONCLUSIONS: The support, counseling, understanding, and explanation given to women by midwives in the postnatal period provides benefits to psychological well-being. Maternity units have a responsibility to develop a service that offers all women the option of attending a session to discuss their labor.
The influence of psychological debriefing on emotional adaptation in women following early miscarriage: a preliminary study.
About a fifth of pregnancies end in miscarriage, leading to emotional consequences, such as anxiety and depression, which may last for a number of months. Despite this, women are not routinely provided with follow-up care. Anecdotal evidence suggests that follow-up focusing on emotional experiences may have beneficial effects. This study tests the hypothesis that the psychological debriefing process has a positive influence on emotional adaptation. Women were assessed, using the Hospital Anxiety and Depression Scale and Impact of Events Scale, at one week and four months post-miscarriage. Half the women also received psychological debriefing at two weeks. Intrusion and avoidance scores were initially as high as those of post-trauma victims, but had significantly decreased by four months. Depression was not detected at any time point, but anxiety was significantly higher than community sample estimates at one week and four months. Psychological debriefing was perceived to be helpful, but did not influence emotional adaptation. A number of hypotheses are provided to explain these results. Outcome scores at one week significantly predicted outcome at four months, suggesting that early assessment would be important in determining which women should be offered intervention.
Stress debriefing after childbirth: a randomised controlled trial.
OBJECTIVE: To test whether critical incident stress debriefing after childbirth reduces the incidence of postnatal psychological disorders.
DESIGN: Randomised single-blind controlled trial stratified for parity and delivery mode.
SETTING: Two large maternity hospitals in Perth.
PARTICIPANTS: 1745 women who delivered healthy term infants between April 1996 and December 1997 (875 allocated to intervention and 870 to control group).
INTERVENTION: An individual, standardised debriefing session based on the principles of critical incident stress debriefing carried out within 72 hours of delivery.
MAIN OUTCOME MEASURES: Diagnosis of stress disorders or depression in the 12 months postpartum, using structured psychological interview and criteria of the Diagnostic and statistical manual of mental disorders, 4th edition.
RESULTS: Follow-up information was available for 1730 women (99.1%), 482 of whom underwent psychological interview. There were no significant differences between control and intervention groups in scores on Impact of Events or Edinburgh Postnatal Depression Scales at 2, 6 or 12 months postpartum, or in proportions of women who met diagnostic criteria for a stress disorder (intervention, 0.6% v control, 0.8%; P = 0.58) or major or minor depression (intervention, 17.8% v control, 18.2%; relative risk [95% CI], 0.99 [0.87-1.11]) during the postpartum year. Nor were there differences in median time to onset of depression (intervention, 6 [interquartile range, 4-9] weeks v control, 4 [3-8] weeks; P = 0.84), or duration of depression (intervention, 24 [12-46] weeks v control, 22 [10-52] weeks; P = 0.98).
CONCLUSIONS: There is a high prevalence of depression in women during the first year after childbirth. A session of midwife-led, critical incident stress debriefing was not effective in preventing postnatal psychological disorders, but had no adverse effects.
A randomized controlled trial of individual psychological debriefing for victims of violent crime.
BACKGROUND: It has been suggested that giving people the opportunity talk about a traumatic experience may prevent the development of later disorder. We tested the efficacy of two brief interventions, education and psychological debriefing, designed to prevent adverse psychological reactions to criminal victimization.
METHODS: Individuals who had been the victims of a violent crime within the past month were written to and invited to take part in a study of their attitudes to crime and punishment: 2161 were contacted and 243 replied, of whom 157 were eligible and were randomly assigned either to an education condition, to a psychological debriefing plus education condition, or to an assessment only condition. Education involved providing information about normal post-traumatic reactions. Debriefing involved in-depth probing about events, thoughts and feelings experienced during the crime. Subjects were recruited from police and hospital sources and interviewed in their own homes: 138 were followed up at 6 months, and 92 at 11 months.
RESULTS: Outcome was assessed using a DSM-III-R diagnosis of PTSD, the Post-traumatic Symptom Scale, the Impact of Event Scale and the Beck Depression Inventory. All groups improved over time but there were no between-group differences.
CONCLUSIONS: No evidence was found to support the efficacy of brief one-session interventions for preventing post-traumatic symptoms in individual victims of violent crime.
Emotional or educational debriefing after psychological trauma. Randomised controlled trial.
BACKGROUND: Recent studies show that individual single-session psychological debriefing does not prevent and can even aggravate symptoms of post-traumatic stress disorder (PTSD).
AIMS: We studied the effect of emotional ventilation debriefing and educational debriefing v. no debriefing on symptoms of PTSD, anxiety and depression.
METHOD: We randomised 236 adult survivors of a recent traumatic event to either emotional ventilation debriefing, educational debriefing or no debriefing (control) and followed up at 2 weeks, 6 weeks and 6 months.
RESULTS: Psychiatric symptoms decreased in all three groups over time, without significant differences between the groups in symptoms of PTSD (P=0.33). Participants in the emotional debriefing group with high baseline hyperarousal score had significantly more PTSD symptoms at 6 weeks than control participants (P=0.005).
CONCLUSIONS: Our study did not provide evidence for the usefulness of individual psychological debriefing in reducing symptoms of PTSD, anxiety and depression after psychological trauma.
Randomised controlled trial of midwife led debriefing to reduce maternal depression after operative childbirth.
OBJECTIVE: To assess the effectiveness of a midwife led debriefing session during the postpartum hospital stay in reducing the prevalence of maternal depression at six months postpartum among women giving birth by caesarean section, forceps, or vacuum extraction.
DESIGN: Randomised controlled trial.
SETTING: Large maternity teaching hospital in Melbourne, Australia.
PARTICIPANTS: 1041 women who had given birth by caesarean section (n= 624) or with the use of forceps (n= 353) or vacuum extraction (n= 64).
MAIN OUTCOME MEASURES: Maternal depression (score >/=13 on the Edinburgh postnatal depression scale) and overall health status (comparison of mean scores on SF-36 subscales) measured by postal questionnaire at six months postpartum.
RESULTS: 917 (88%) of the women recruited responded to the outcome questionnaire. More women allocated to debriefing scored as depressed six months after birth than women allocated to usual postpartum care (81 (17%) v 65 (14%)), although this difference was not significant (odds ratio=1.24, 95% confidence interval 0.87 to 1.77). They were also more likely to report that depression had been a problem for them since the birth, but the difference was not significant (123 (28%) v 94 (22%); odds ratio=1. 37, 1.00 to 1.86). Women allocated to debriefing had poorer health status on seven of the eight SF-36 subscales, although the difference was significant only for role functioning (emotional): mean scores 73.32 v 78.98, t= -2.31, 95% confidence interval -10.48 to -0.84).
CONCLUSIONS: Midwife led debriefing after operative birth is ineffective in reducing maternal morbidity at six months postpartum. The possibility that debriefing contributed to emotional health problems for some women cannot be excluded.
Options:
A: It significantly reduces psychological distress and prevents the onset of PTSD.
B: It has no significant effect on psychological distress or the prevention of PTSD.
C: It increases the risk of developing PTSD in the long term.
D: It reduces general psychological morbidity, depression, and anxiety.
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B
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97
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
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What were the findings regarding the use of calcium channel blockers in patients with acute traumatic brain injury, including those with traumatic subarachnoid haemorrhage? Please answer this question based on the information provided below:
A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury.
A double blind, placebo controlled trial of nicardipine in the treatment of high Doppler Flow Velocity (DFV) following severe head injury (Glasgow Coma Score (GSC) less than or equal to 8) was performed. Thirty patients with high DFV (greater than or equal to 100 cm/s for 6 h duration) on transcranial Doppler ultrasound, were treated with nicardipine or placebo for 24 h (2.5 mg/h, increasing in steps of 2.5 mg/h at 2 h intervals (maximum rate 7.5 mg/h) depending on response of DFV). DFV was measured hourly for 24 h and then every 12 h for 2 days. Nicardipine significantly reduced DFV below the threshold of 100 cm/s (16/19 cf placebo 3/11, chi-square p less than 0.001). In the nicardipine treated group maximum DFV was significantly reduced (p less than 0.001) and time with DFV below 100 was significantly longer. Rises in DFV were significantly reduced by the drug if the DFV was normal at the time of entry. High DFV returned on cessation of the infusion. No unexpected or adverse side effects were seen. No clinical benefit was demonstrable.
A trial of the effect of nimodipine on outcome after head injury.
We performed a randomised prospective double blind trial to study the effect of the calcium antagonist nimodipine on the outcome of head injured patients. The subjects were not obeying commands at the time of entry to the study, within 24 hours of injury. One hundred and seventy-five patients received nimodipine IV, 2 mg per hour for up to 7 days and 176 received placebo. The two groups were well matched for important prognostic features. Six months after injury 93 (53%) of the nimodipine group and 86 (49%) of the control group had a favourable outcome (moderate/good recovery). The relative increase in favourable outcomes (8%) was not significant but is compatible (95% C.I.) with an increase in favourable outcomes in treated patients by 33% or a decrease by 12%. Nimodipine was well tolerated and there were few adverse reactions; means of systolic and diastolic blood pressures and the intracranial pressure did not differ between the groups. It is unlikely that nimodipine has a marked effect on outcome (ie an increase in favourable outcome of greater than 15%) after head injury of this severity but the study does not exclude a modest but clinically useful benefit.
A randomized trial of nimodipine in severe head injury: HIT I. British/Finnish Co-operative Head Injury Trial Group.
We studied the efficacy of nimodipine in severely head-injured patients in a randomized study. Of 176 patients who received nimodipine, 2 mg/h iv for 2 day, 53% had a favorable outcome (moderate or good recovery). Of 175 control patients, 49% had a favorable outcome. This difference was not statistically significant but does not exclude the possibility that a study of a larger number of patients could show a clinically useful benefit.
The effect of nimodipine on outcome after head injury: a prospective randomised control trial. The British/Finnish Co-operative Head Injury Trial Group.
To study the effect of nimodipine on the outcome of head injury, three hundred and fifty-two patients who were not obeying commands were randomised to placebo or nimodipine (2 mg per hour intravenously for 7 days). The 2 groups were well matched for important prognostic features. Six months after injury, more of the patients who were given nimodipine had a favourable outcome (moderate/good recovery) than in the control group, but the increase in favourable outcome (8%) was not significant statistically.
A multicenter trial of the efficacy of nimodipine on outcome after severe head injury. The European Study Group on Nimodipine in Severe Head Injury.
Between January 1, 1989, and June 30, 1991, 852 severely head-injured patients were entered into a prospective placebo-controlled trial of the efficacy of nimodipine administration. The patients could not obey commands at the time of entry into the trial, which was within 12 hours after the start of the inability to obey commands and within 24 hours of injury. The main hypothesis that nimodipine would increase the percentage of patients with a favorable outcome (moderate disability or good recovery) from 50% to 60% was rejected. A trend toward a favorable effect was seen in patients who exhibited traumatic subarachnoid hemorrhage (SAH) on the computerized tomography (CT) scan obtained prior to entry into the study. The effect was statistically significant in those patients who complied with all protocol requirements. This finding is consistent with the effect of nimodipine on secondary ischemia following spontaneous SAH. The results of the study warrant a clinical trial of the efficacy of nimodipine in severely head-injured patients who show traumatic SAH on the initial CT scan.
Clinical significance of the finding of subarachnoid blood on CT scan after head injury.
The population analysed consisted of 268 out of 819 patients of a European nimodipine multicentre trial on severe head injury, whose first CT scan after injury showed signs of subarachnoid bleeding. The study demonstrated the importance of traumatic subarachnoid haemorrhage (tSAH) per se as a prognostic factor. The outcome of patients with tSAH is significantly worse than that of patients whose first CT does not show subarachnoid blood (noSAH). The outcome was unfavourable (dead, persistent vegetative state, severe disability) in 60% of tSAH patients compared to 30% of noSAH patients (p < 0.001). The difference in mortality was 42% vs. 14% (p < 0.001). The six month follow-up of tSAH patients complying with the study protocol and treated with intravenous nimodipine, 2 mg per hour for 7 days, showed a statistically significant reduction of unfavourable outcome from 66% to 51% (p < 0.05), compared to placebo treated patients.
Nimodipine in traumatic subarachnoid haemorrhage: a re-analysis of the HIT I and HIT II trials.
Two large randomised controlled trials have been performed to study the effect of the calcium antagonist nimodipine on the outcome of severe head injury, HIT I [1] amd HIT II [4]. Both trials showed a modest and statistically non-significant increase in the proportion of favourable outcomes in patients treated with nimodipine. A subgroup analysis of the HIT II trial [4, 5] suggested, however, that there could be a substantial protective effect of nimodipine in patients with traumatic subarachnoid haemorrhage (SAH). This report provides a re-analysis of the HIT I data to see whether it provides a re-analysis of the HIT I data to see whether in HIT II. This involved performing a central review of the CT scans for the HIT I patients, to identify those individuals with evidence of traumatic SAH. The sample size was small, but the HIT I data gave no support to the hypothesis that nimodipine is protective in the traumatic SAH subgroup, where 69% of patients had a poor outcome on placebo and 74% of patients had a poor outcome on nimodipine. The data do not exclude the possibility of a clinically relevant beneficial effect of nimodipine in the traumatic SAH subgroup, but further data are required to provide a definitive answer. In addition, we present a pooled analysis of the data from the two trials, which suggests that the overall benefit of treating unselected head injured patients with nimodipine is unlikely to be clinically relevant.
Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group.
A prospective, randomized, double-blind, placebo-controlled study of nimodipine used to treat traumatic subarachnoid hemorrhage (tSAH) was conducted in 21 German neurosurgical centers between January 1994 and April 1995. One hundred twenty-three patients with tSAH appearing on initial computerized tomography (CT) scanning were entered into the study. Requirements for inclusion included age between 16 and 70 and admission into the study within 12 hours after head injury, regardless of the patient's level of consciousness. Eligible patients received either a sequential course of intravenous and oral nimodipine or placebo treatment for 3 weeks. Patients were closely monitored using clinical neurology, computerized tomography, laboratory, and transcranial Doppler ultrasound parameters. Patients treated with nimodipine had a significantly less unfavorable outcome (death, vegetative survival, or severe disability) at 6 months than placebo-treated patients (25% vs. 46%, p = 0.02). The relative reduction in unfavorable outcome in the nimodipine-treated group was even higher (55%, p = 0.002) when only patients who complied with the protocol were considered.
[A controlled, double-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury].
INTRODUCTION: One of the factors involved in the occurrence of ischemic cerebral lesions following head injury is cerebral vasospasm. We analyze the effect of intravenous nicardipine on the prevention and treatment of posttraumatic cerebral vasospasm.
PATIENTS AND METHODS: We made a placebo-controlled, randomised, double-blind pilot study of the effect of nicardipine (intravenously 5 mg/hour for one week) on patients with moderate or severe head injury who presented with cerebral vasospasm, defined as an average Doppler flow velocity (DFV) of 100 cm/second or more. The main variable assessed was the evolution of the DFV and the secondary criteria were the evolution of the arterial blood pressure, coma scales, the findings on the Glasgow Coma Scale and the safety of the drug.
RESULTS: Eleven patients were included in each homogeneous group. The DFV was found to have become normal on the first day of treatment with nicardipine and on the third day with the placebo (p = 0.023). During the first day of treatment the percentage of cerebral hemispheres diagnosed as having suspected spasm was 11.1% for nicardipine and 64.3% for the placebo (p = 0.02881). The average time for recovery (DFV < 100 cm/second) was 3.33 days with the placebo and 1.22 days with nicardipine (p = 0.0039). The patients treated with nicardipine had 8.89 times more chance of recovery from vasospasm. The incidence of adverse effects was greater with the placebo (p = 0.014).
CONCLUSION: Nicardipine is effective in the reversal and prevention of increased Doppler flow velocity in patients with moderate or severe head injury.
Options:
A: Calcium channel blockers significantly reduced the risk of death and severe disability in all patients with acute traumatic brain injury.
B: Calcium channel blockers showed no significant effect on the risk of death in patients with acute traumatic brain injury, but showed a beneficial effect in reducing death and severe disability in patients with traumatic subarachnoid haemorrhage.
C: Calcium channel blockers significantly increased the risk of adverse reactions without any beneficial effects on mortality or disability in patients with acute traumatic brain injury.
D: Calcium channel blockers had a significant beneficial effect on reducing the risk of death in all patients with acute traumatic brain injury.
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B
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98
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evidence_summarization
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You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What was the conclusion regarding the effectiveness of hyperventilation therapy on death and neurological disability following acute traumatic brain injury? Please answer this question based on the information provided below:
Traumatic brain tissue acidosis: experimental and clinical studies.
We have been focusing on potential metabolic derangement associated with severe head injury and a clinical trail directed toward treating brain tissue acidosis is currently underway. More specifically, we based this study on the hypothesis that following brain trauma brain tissue acidosis develops which may contribute to the prolongation of coma and neurologic deficit. Tromethamine (THAM), a safe and low toxicity agent which buffers in major part by causing a hypocapnic alkalosis, was selected for trial. Patients admitted with GCS < 8 were randomized into one of three arms: control: THAM plus hyperventilation; hyperventilation alone. Each regimen was maintained for 5 days post injury. Our analysis of 3 and 6 months Glasgow outcome score showed that prophylactic hyperventilation retards recovery, and the use of THAM overcomes the apparent deleterious effects of hyperventilation. One explanation is that the reduced ICP instability observed in THAM treated patients may account for this improvement. Is THAM effective in buffering traumatized brain tissue? What factors account for improvement in ICP stability? We addressed these questions in experimental studies utilizing MR spectroscopy to measure brain lactate production and tissue pH in fluid percussed anaesthetized cats. The protocol was designed to match our clinical trial, and brain injured animals were randomized into control, THAM, and hyperventilated groups. We observed that brain lactate production increased with trauma and remained above control at 8 hrs post injury. Lactate production in THAM treated animals was not elevated. Highest lactate production was associated with injured animals treated with sustained hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.
There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)
Options:
A: Hyperventilation therapy significantly reduces mortality and improves neurological recovery.
B: Hyperventilation therapy shows a beneficial effect on mortality but does not improve neurological recovery.
C: Hyperventilation therapy significantly increases the risk of death and severe disability.
D: The data available are inadequate to assess the potential benefit or harm of hyperventilation therapy.
|
D
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99
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evidence_summarization
|
You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.
|
What were the findings of the study regarding the effectiveness of allopurinol in the treatment of chronic prostatitis? Please answer this question based on the information provided below:
Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study.
PURPOSE: Nonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion.
MATERIALS AND METHODS: We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups.
RESULTS: Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort.
CONCLUSIONS: Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3-month period at each episode to relieve the symptoms of nonbacterial prostatitis.
Options:
A: Allopurinol significantly improved patient-reported discomfort, investigator-graded prostate pain, and biochemical parameters without significant side effects.
B: Allopurinol had no significant effect on patient-reported discomfort, investigator-graded prostate pain, or biochemical parameters.
C: Allopurinol significantly worsened patient-reported discomfort and investigator-graded prostate pain, but improved biochemical parameters.
D: Allopurinol had significant side effects that led to a high dropout rate among patients.
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A
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