Context: Growth hormone (GH)-secreting pituitary adenoma is a severe endocrine disease. Surgery is the currently recommended primary therapy for patients with GH-secreting tumours. However, non-surgical therapy (pharmacological therapy and radiation therapy) may be performed as primary therapy or may improve surgical outcomes.

To assess the effects of surgical and non-surgical interventions for primary and salvage treatment of GH-secreting pituitary adenomas in adults.

Randomised controlled trials (RCTs) and quasi-RCTs of more than 12 weeks' duration, reporting on surgical, pharmacological, radiation, and combination interventions for GH-secreting pituitary adenomas in any healthcare setting.

Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma.

Abstract: The aim of this study was to verify whether treatment with slow-release lanreotide (SRL) before surgery is useful in the management of patients with GH-secreting pituitary macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups. Ten patients (group 1: 2 males and 8 females aged 44.5 +/- 4.3 years) underwent surgery via transsphenoidal access. Only one of them was cured by surgery, whereas the other nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females aged 43.2 +/- 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced the normalization of GH and IGF-1 levels in four group 2 patients - three of them had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group 1 showed a significant decrease of mean IGF-1 (580 +/- 63 vs. 789 +/- 64 ng/ml, p < 0.02), but not of GH values (26.1 +/- 9.8 vs. 44.8 +/- 19.3 ng/ml, NS); the cured patient was excluded from the following evaluations. Group 2 showed an evident, but not significant, decrease of both GH and IGF-1 values compared to values measured at the end of medical treatment (GH: 22.4 +/- 9.7 vs. 7.7 +/- 4.7 ng/ml, NS. IGF-1: 570 +/- 69 vs. 402 +/- 58 ng/ml, NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg was administered every 14 days for three months and then every 10 days until the 6th month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly in group 1 vs. group 2 (GH: 29.3 +/- 10.5 vs. 43.4 +/- 22.0 ng/ml; IGF-1: 633 +/- 38 vs. 778 +/- 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1 levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 +/- 5.4 ng/ml, p < 0.05. IGF-1: 540 +/- 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1 values was evident during the 2nd trimester (GH: 6.1 +/- 3.0 ng/ml, p < 0.05. IGF-1: 433 +/- 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL therapy, were also significantly lower than levels measured at the end of the 1st trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased at the end of the 1st trimester (GH: 27.2 +/- 12.1 ng/ml, NS. IGF-1: 698 +/- 74 ng/ml, NS), whereas only serum IGF-1 (570 +/- 69 ng/ml, p < 0.05) was significantly reduced during the 2nd trimester of SRL (GH: 22.4 +/- 9.7 ng/ml, NS). Serum GH and IGF-I fell in the normal range in 4 patients in group 1 and one in group 2 at the end of the second trimester of SRL therapy. Independently of the trial applied, the mean clinical score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2: p < 0.0001). In both groups, the proportion of patients complaining of headache and tissue swelling and the score level of headache, tissue swelling and excessive sweating decreased significantly. In group 1 the score level of fatigue and arthralgia also decreased significantly. In conclusion, this study proves that in patients with GH-secreting pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the clinical and biochemical outcome and reduces the prevalence of hypopituitarism due to surgery.

Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial.

Abstract:
Surgery is the primary treatment of acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed.

Our objective was to investigate whether 6-month preoperative treatment with octreotide improves the surgical outcome in newly diagnosed acromegalic patients.

During a 5-yr period (1999-2004), all newly diagnosed acromegalic patients between 18 and 80 yr of age in Norway were screened and invited to participate in the study. A total of 62 patients was included in the Preoperative Octreotide Treatment of Acromegaly study.

After a baseline evaluation, patients were randomized directly to transsphenoidal surgery (n = 30) or pretreatment with octreotide (n = 32) 20 mg im every 28th day for 6 months before transsphenoidal surgery. Cure was evaluated 3 months postoperatively primarily by IGF-I levels.

According to the IGF-I criteria, 14 of 31 (45%) pretreated patients vs. seven of 30 (23%) patients with direct surgery were cured by surgery (P = 0.11). In patients with microadenomas (< or = 10 mm), one of five (20%) pretreated vs. three of five (60%) with direct surgery were cured (P = 0.52). In patients with macroadenomas, 13 of 26 (50%) pretreated vs. four of 25 (16%) with direct surgery were cured (P = 0.017).

Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.

Does octreotide treatment improve the surgical results of macro-adenomas in acromegaly? A randomized study.

Abstract: It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n = 11, group A) and without (n = 13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470 +/- 160 micrograms Octreotide for 16.5 +/- 10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38.9 +/- 34.1 to 6.8 +/- 4.9 micrograms/l and from 2.7 +/- 1 to 1.7 +/- 0.7 arbitrary units respectively. The adenoma-shrinkage from 5.9 +/- 5.8 to 4.7 +/- 4.9 cm3 missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of > 50 micrograms/l. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.

A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly.

Abstract:
At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals).

Twelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6-24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7-21-day intervals, median 10 days - every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements. OC-LAR was administered i.m. at 28-day intervals six times at the dosage of 20 mg for the first three times and 10 or 30 mg for the last three times (according to individual GH/IGF-I responses). GH (mean of three, hourly samples) and IGF-I concentrations were evaluated on the same day as each administration of the drug, before its injection.

GH and IGF-I values were significantly decreased by LSR treatment. GH decreased from 41.6 +/- 14.6 microg/l (mean +/- s.e.) to 7.2 +/- 1.5 microg/l (P < 0.02), whereas IGF-I values declined from 959 +/- 95 microg/l to 460 +/- 61 microg/l (P < 0.00001), expressed as absolute values, and from 287 +/- 30% to 137 +/- 19% expressed as percentage of the upper limit of normal range (% ULNR). At the end of the last cycle, OC-LAR treatment achieved a significant further suppression both in GH (to 5.1 +/- 1.1 microg/l, P < 0.05 compared with LSR) and in IGF-I concentrations (to 374 +/- 60 microg/l, P<0.05 compared with LSR, and to 112 +/- 19% as % ULNR). LSR decreased GH concentrations to less than 2.5 microg/l in one patient and normalized IGF-I concentrations in four patients. OC-LAR decreased GH concentrations to less than 2.5 microg/l in four patients and normalized or near-normalized IGF-I concentrations (i.e. to < 110% ULNR) in eight patients.

These preliminary results show that the once-monthly OC-LAR administration schedule proved more efficacious than LSR given every 7-21 days, in a greater number of acromegalic patients.

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.

Abstract:
Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.

We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.

The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.

On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs.

Abstract: Transsphenoidal surgical resection is the primary therapy for acromegaly caused by GH secreting pituitary adenomas. Medical therapy for patients not controlled by surgery includes primarily somatostatin analogs and secondarily dopamine agonists, both of which inhibit pituitary growth hormone secretion. A novel GH receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits peripheral insulin-like growth factor-1 generation. Six patients resistant to maximal doses of octreotide therapy received pegvisomant - three received placebo or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and pegvisomant 10-20 mg/d for 12 weeks. Thereafter, all patients received daily pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total IGF-1 levels were normalized in all six acromegalic patients previously shown to be resistant to somatostatin analogs via a novel mechanism of peripheral GH receptor antagonism. The GH receptor antagonist is a useful treatment for patients harboring GH-secreting tumors who are resistant to octreotide.

Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration.

Abstract:
The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10-14 days, respectively, are applicable to all patients.

To determine the optimum intervals between depot injections of either octreotide LAR and lanreotide for the suppression of serum GH and IGF-I in patients with acromegaly. Twenty-seven patients with acromegaly were randomly allocated to receive either three injections at 4 week intervals of octreotide LAR (n = 18) or five injections at 14 day intervals of lanreotide (n = 11); two patients participated in both arms. Prior to the first injection, at 4 and 6 weeks after the last injection of LAR, and at 10, 14 and 21 days after the last injection of lanreotide, serum mean GH and IGF-I levels were measured.

In the LAR-treated group, at 4 and 6 weeks after the third injection 13 patients (72%) and 12 patients (67%), respectively, had a mean GH < 5 mU/l. IGF-I was normalized in 12 and 11 patients at these times. In the lanreotide-treated group, five (45%), four (36%) and three (27%) patients, respectively, had a GH < 5 mU/l at 10, 14 and 21 days after the last injection and eight, six and five patients had a normal serum IGF-I.

There is marked variability in individual patient responses to depot somatostatin analogues. The establishment of optimal drug intervals requires careful assessment. For octreotide LAR many patients may be as adequately controlled with 6 weekly injections as with 4 weekly injections. It is important to measure serum GH profiles at intervals after initiating therapy with these drugs to individualize doses for each patient and hence minimize cost.

Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly.

Abstract:
The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.

Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant.

Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively).

This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.

Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant.

Abstract: Acromegaly is associated with premature cardiovascular mortality. GH replacement therapy decreases inflammatory markers of cardiovascular risk, but little is known about these markers in patients with acromegaly. The GH receptor antagonist, pegvisomant, reduces IGF-I levels in 98% of patients treated. We investigated the effects of GH receptor blockade on inflammatory and other cardiovascular risk markers in active acromegaly. Forty-eight patients with acromegaly and 47 age- and body mass index-matched controls were included. The study consisted of 3 parts: a cross-sectional study, a prospective randomized 12-wk placebo-controlled study, and a longitudinal open-label study of up to 18 months of pegvisomant treatment. After baseline evaluation, patients with acromegaly were randomized to placebo (n = 14), 10 mg (n = 12), 15 mg (n = 10), or 20 mg (n = 12) daily pegvisomant for 12 wk. Subsequently, all patients received at least 10 mg pegvisomant daily for up to 18 months, with dose adjustments to achieve a normal IGF-I level. Anthropometry, GH, IGF-I, and pegvisomant levels were measured monthly. C-reactive protein (CRP), IL-6, homocysteine, lipoprotein(a), glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined at baseline, 4 and 12 wk in the placebo-controlled study and at 3-month intervals (during which IGF-I levels were normal) in the longitudinal study. In the cross-sectional study, patients had lower CRP than did controls [median, 0.3 (range, 0.2-0.8) vs. 2.0 (0.6-3.7) mg/liter; P < 0.0001] and had higher insulin [78.6 (55.8-130.2) vs. 54.5 (36.6-77.5) pM, P = 0.0051]. IL-6, homocysteine, triglycerides, lipoprotein(a), LDL cholesterol and HDL cholesterol were not different between groups. In the placebo-controlled study, CRP increased in patients treated with 20 mg pegvisomant, compared with placebo (mean +/- SEM, 13.7 +/- 3.6 vs. 0.5 +/- 3.3 mg/liter; P = 0.010). There were no significant differences in IL-6, homocysteine, glucose, insulin, triglyceride, total cholesterol, LDL cholesterol and HDL cholesterol levels. In the longitudinal open-label study (median duration, 15.6 months), CRP increased by 2.0 +/- 0.5 mg/liter (P = 0.0002). Total cholesterol and triglycerides increased (0.22 +/- 0.11 mM, P = 0.050; and 0.25 +/- 0.09 mM, P = 0.007, respectively), whereas lipoprotein(a) decreased (-70 +/- 33 mg/liter, P = 0.039). Glucose, insulin, homocysteine, HDL cholesterol, and IL-6 did not change. We conclude that patients with active acromegaly have lower CRP and higher insulin levels than healthy controls. Administration of pegvisomant increases CRP levels. We propose that GH secretory status is an important determinant of serum CRP levels, although additional studies are needed to determine the mechanism and significance of this finding.

Presurgical octreotide treatment in acromegaly.

Abstract: The aim of this study was to determine the role of octreotide administration in acromegalic patients as a preparation for selective adenomectomy using transsphenoidal route. Octreotide was administered for 3 to 6 weeks before surgery in 12 patients and for 4 to 39 months in 25 patients. The clinical response was judged as excellent or good in 10 of 12 patients from group I and in 23 of 25 patients from group II. Marked reduction (ie, greater than 50% of initial values) in serum growth hormone (GH) levels was seen in all patients, with levels to less than 5 micrograms/L in 68% of patients and less than 2 micrograms/L in 27%. Insulin-like growth factor 1 (IGF-1) levels decreased to within normal limits in half the cases. During long-term treatment, an escape phenomenon could be seen. Varying degrees of tumor shrinkage were seen in more than 50% of cases. During surgery, with regard to the relative ease or difficulty in removing the tumor, the consistency of the tumor and the separation of normal from pathological tissue, no significant difference was observed between patients given octreotide and those from control series. Morphological changes in adenomatous tissue were rather small. The surgical outcome was similar in the pretreated series as in the control series, except in enclosed adenomas, which showed a tendency to a higher success rate. Since octreotide improves both the clinical condition and hormonal parameters and induces varying degrees of tumor shrinkage, it is potentially useful as an adjunct to surgery. Morphological data suggest that octreotide exercises a functional inhibitory effect on GH release.


Context: Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments.

To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults.

We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups.

[Meibomian gland dysfunction: a comparative study of modern treatments].

Abstract:
To evaluate a thermal pulsation treatment compared to a warming eyelid device for the management of meibomian gland dysfunction.

Thirty patients were randomized into two groups: the first had a treatment with MeiboPatch(®) on a daily basis for three months while the second had a single treatment with LipiFlow(®). The evaluation focused on a classical approach but also on a modern approach of the ocular surface (interferometry lipid layer LipiView(®)), analysis of the tear film by Oquas(®) (osmolarity by TearLab(®)) before treatment, then a month and three months later.

Both treatments proved to be effective with almost three times more functional meibomian glands at 3 months in the LipiFlow group and almost twice more in the MeiboPatch group (P<0.05) but the LipiFlow allows a more rapid improvement at the first month of treatment. Functional scores and classic exploration of the ocular surface except the Schirmer test also undergo a significant improvement in both groups after three months of treatment.

The combination of heat applied to the inner eyelid surface, together with simultaneous expression of the glands, during a single 12-minute treatment shows to be highly effective in treating cases of meibomian gland disease. Whilst results were excellent, and continued lid hygiene remains advised, the benefit of being able to simultaneous address potential compliance issues relating to ongoing treatment is significant. The convenience of a single 12-minute treatment versus an ongoing daily heating regime was shown to be highly desirable and a welcome relief in our patients' busy lifestyles.

Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

Abstract:
The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD).

This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining.

In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant (

A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.

A 6-Week, Prospective, Randomized, Single-Masked Study of Lifitegrast Ophthalmic Solution 5% Versus Thermal Pulsation Procedure for Treatment of Inflammatory Meibomian Gland Dysfunction.

Abstract:
Meibomian gland dysfunction (MGD) is present in most cases of dry eye disease. MGD involves both inflammatory and obstructive etiologies. We compared efficacy and safety of treatment to reduce inflammation (lifitegrast) versus obstruction [thermal pulsation procedure (TPP)] in patients with inflammatory MGD over 42 days.

This was a single-center, 6-week, prospective, randomized, single-masked study of adults with inflammatory MGD, defined as having all of the following: burning, stinging, dryness; thickened secretions or occlusion of glands; eyelid redness; and elevated matrix metalloproteinase-9. Patients received lifitegrast ophthalmic solution 5% twice daily for 42 days or one TPP treatment at day 0. Seven symptoms and 8 objective measures of dry eye disease were assessed.

Overall, 40 of 50 randomized patients (80%) were women with mean (SD) age 65.8 (8.9) years. Lifitegrast-treated (n = 25) versus TPP-treated (n = 25) patients had greater improvement from baseline to day 42 in eye dryness [mean (SD) change from baseline: -1.05 (0.79), lifitegrast; -0.48 (0.96), TPP; P = 0.0340], corneal staining [-0.55 (0.80), lifitegrast; 0.12 (1.09), TPP; P = 0.0230], and eyelid redness [-0.77 (0.43), lifitegrast; -0.38 (0.58), TPP; P = 0.0115]; trend favored lifitegrast for best corrected visual acuity and gland patency. Unexpectedly, TPP treatment did not improve lipid layer thickness or gland patency compared with lifitegrast. No adverse events were reported.

Although MGD is often considered a disease of gland obstruction, these findings demonstrate antiinflammatory treatment with lifitegrast significantly improved patient symptoms and signs compared with treatment for obstruction (TPP). Lifitegrast should be included in treatment for inflammatory MGD.

Comparison of the iLUX and the LipiFlow for the Treatment of Meibomian Gland Dysfunction and Symptoms: A Randomized Clinical Trial.

Abstract:
To compare the effects of eyelid treatment with the iLUX MGD Treatment System and the LipiFlow Thermal Pulsation System on objective and subjective parameters of meibomian gland function and symptoms.

In this randomized, open-label, controlled, multicenter clinical trial, both eyes of 142 patients aged ≥18 years with Ocular Surface Disease Index (OSDI) scores ≥23, total meibomian gland scores (MGS) ≤12 in the lower eyelid of each eye, and tear break-up time (TBUT) <10 s were randomized 1:1 to iLUX or LipiFlow treatment, with stratification by test center. The primary effectiveness endpoints were changes in total MGS (masked) and TBUT from baseline to 4 weeks. The secondary effectiveness endpoint was changed in OSDI score from baseline to 4 weeks.

Both devices significantly improved effectiveness outcomes, with no differences between the two devices. At the 4-week visit, mean MGS, TBUT, and OSDI scores improved at least 16.9 ± 11.5, 2.6 ± 3.2 s, and 28.0 ± 22.8, respectively, across treatment groups and treated eyes. Four device/procedure-related events occurred in the iLUX group, compared with none in the LipiFlow group, but there were no device-related adverse events that involved changes in lid margins, eyelids, or lash integrity. Corneal staining, intraocular pressure, and visual acuity did not differ in the two groups.

Both treatments produced significant improvements in meibomian gland function and symptoms. For all effectiveness measures, there were no statistically significant differences between the two treatments.

The Efficacy Between Conventional Lid Hygiene and Additional Thermal Pulsatile System in Meibomian Gland Dysfunction Patients Treated with Long-Term Anti-Glaucoma Medications in a Randomized Controlled Trial.

Abstract:
To evaluate the efficacy of additional thermal pulsatile system compared to standard lid hygiene alone in meibomian gland dysfunction (MGD) patients who are using long-term anti-glaucoma medications.

Well-controlled glaucoma patients who used anti-glaucoma medications for at least 1 year and had MGD were enrolled and randomized between a study group who received thermal pulsatile system (Lipiflow

Of 60 participants who underwent randomization, 48 completed the study. At the 6-month mark, this study could not demonstrate any significant difference between groups in both primary and secondary outcomes. However, there was significant improvement from baseline in both groups of the following outcomes: meibomian gland expression score, OSDI score, LLT, and meibography score. No serious adverse event was found in this study.

An additional single thermal pulsatile system treatment with standard lid hygiene significantly improved meibomian gland assessment score and subjective symptoms at 6 months. Any difference between additional thermal pulsatile system treatment and lid hygiene alone was not found in this study. The results may suggest more chronic MGD and more damaged meibomian gland induced by long-term anti-glaucoma medications.

TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.

Abstract:
#PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction.
#METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month.
#RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness).
#CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

Effect of a Novel Thermostatic Device on Meibomian Gland Dysfunction: A Randomized Controlled Trial in Chinese Patients.

Abstract:
Meibomian gland dysfunction (MGD) is a common eye condition that causes excessive evaporation of tears by changing the tear film composition. Current treatments often fail to produce satisfactory results, which is mostly due to poor patient adherence. This study aimed to evaluate the effectiveness and safety of the MiBoFlo Thermoflo® on both subjective symptoms and objective signs in Chinese patients with MGD.

This prospective, randomized, controlled clinical trial included 108 eyes of 54 patients with MGD who were recruited in Beijing Tongren Hospital and randomized 1:1 to MiBoFlo (n = 54 eyes) or LipiFlow® (n = 54 eyes) treatment group. In the MiBoFlo group, patients received three 10-min treatments, each spaced 2 weeks apart, and the treatment was followed by eyelid compression each time. Patients in the LipiFlow group received a single 12-min treatment. The primary parameters measured included changes in Ocular Surface Disease Index (OSDI) score, Meibomian Glands Yielding Liquid Secretion (MGYLS) score, and Meibomian Glands Secretion (MGS) score from baseline to 2 months. The secondary parameters included tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), corneal fluorescein staining (CFS), and meibomian glands (MG) loss from baseline to 2 months. Safety parameters include visual acuity (VA), intraocular pressure (IOP), anterior segment, and facial skin.

The OSDI, MGYLS, and MGS scores all improved from baseline to 1 month in both MiBoFlo and LipiFlow groups, and these improvements were maintained at 2 months. CFS score, NIKBUT, and MG loss showed no significant change in both groups.

As a portable and comfortable device, MiBoFlo can improve the treatment of MGD and achieve a sustained improvement in both symptoms and meibomian gland function lasting at least 2 months.

Comparison of Two Thermal Pulsation Systems in the Treatment of Meibomian Gland Dysfunction: A Randomized, Multicenter Study.

Abstract:
#SIGNIFICANCE: Given the significance of meibomian gland dysfunction subjects in evaporative dry eye, its chronic and progressive nature, limited promising treatment options, and novel treatment techniques are important. This randomized clinical study evaluated the noninferiority of SYSTANE iLux with LipiFlow in meibomian gland dysfunction treatment at 12 months.
#PURPOSE: This study aimed to demonstrate noninferiority of SYSTANE iLux compared with LipiFlow at 12 months after single treatment in meibomian gland dysfunction subjects with evaporative dry eye.
#METHODS: In this prospective, randomized, multicenter, assessor-masked, parallel-group trial, subjects (N = 236; aged ≥18 years) with meibomian gland score (MGS) of ≤12 in lower eyelids, noninvasive tear breakup time (NITBUT; first breakup) of <10 seconds, and Impact of Dry Eye on Everyday Life-Symptom Bother (IDEEL-SB) module score of >16 were randomized (1:1) to receive SYSTANE iLux (n = 119) or LipiFlow (n = 117). Subjects attended a total of eight visits, including screening, treatment, and follow-up visits at 2 weeks and at 1, 3, 6, 9, and 12 months/exit, to evaluate change from baseline in MGS, NITBUT, IDEEL-SB module score, and safety outcomes.
#RESULTS: A total of 227 subjects completed the study (mean ± standard deviation age, 57.3 ± 13.8 years). At 12 months, least squares mean change from baseline in MGS was similar between iLux and LipiFlow (17.4 ± 1.97 vs. 17.8 ± 1.98). Noninferiority of SYSTANE iLux compared with LipiFlow in change from baseline in MGS (95% lower confidence limit of least squares mean difference, >-5), NITBUT (>-2.5 seconds), and IDEEL-SB score (95% upper confidence limit, <12) was achieved at all post-treatment visits. No other serious ocular or device-related adverse events were reported.
#CONCLUSIONS: The treatment outcomes with SYSTANE iLux were noninferior to LipiFlow during the 12-month follow-up in subjects with dry eye-associated meibomian gland dysfunction.

A Comparison of TearCare and Lipiflow Systems in Reducing Dry Eye Disease Symptoms Associated with Meibomian Gland Disease.

Abstract:
To compare TearCare and Lipiflow systems in the ability to reduce the symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD).

In this multicenter, masked, randomized-controlled trial, 235 subjects received a single TearCare treatment (n = 115) or a single LipiFlow treatment (n = 120) and were followed for 1-month post-treatment. DED symptoms were assessed using the Ocular Surface Disease Index (OSDI), Symptom Assessment in Dry Eye (SANDE), and Eye Dryness (ED) questionnaires at baseline and at 1 month. Post-hoc subgroup analysis was conducted on subjects with less severe and more severe gland obstruction determined by baseline meibomian gland secretion score (MGSS).

TearCare system significantly improved total OSDI, SANDE, and ED scores from baseline (

TearCare provides significant DED symptom relief at 1 month after a single treatment. Outcomes were consistent in OSDI, SANDE, and ED assessments. In subjects with more severe gland dysfunction, TearCare performed significantly better than LipiFlow in improving quality of vision and overall DED symptom frequency determined by OSDI and SANDE.

NCT03857919.

Efficacy and Safety evaluation of a single thermal pulsation system treatment (Lipiflow

Abstract:
#PURPOSE: Evaluate the efficacy and safety of LipiFlow
#METHODS: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow
#RESULTS: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number.
#CONCLUSION: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months.


Context: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011.

To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN.

Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included.

Combined therapy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for paediatric patients with severe IgA nephropathy--is it relevant for adult patients?

Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis.

Abstract: Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation. To clarify whether administration of vitamin K, which enhances bone formation, prevents prednisolone-induced loss of bone mineral density (BMD), a randomized, prospective, controlled study was conducted on 20 patients with chronic glomerulonephritis scheduled for treatment with prednisolone. All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone (maximum of 40 mg) for 4 weeks, tapering to 20 mg/day over approximately 6 weeks. Ten patients received prednisolone alone (Group 1), and the other 10 patients received prednisolone plus 15 mg of menatetrenone, vitamin K, three times per day (Group 2). BMD of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and biochemical markers of bone metabolism in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone. In Group 1, treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 +/- 0.12 to 1.10 +/- 0.11 g/cm2 (P = 0.0029). Serum intact osteocalcin and procollagen type I C-peptide (PICP) concentrations, biochemical markers of bone formation, were markedly reduced. A biochemical marker of bone resorption, urinary excretion of deoxypyridinoline, was significantly reduced. In Group 2, prednisolone-induced reduction of BMD was prevented by menatetrenone administration (1.09 +/- 0.09 to 1.07 +/- 0.07 g/cm2, P = 0.153). Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration and urinary excretion of deoxypyridinoline. Thus, treatment with prednisolone resulted in loss of BMD of the lumbar spine associated with suppression of both bone formation and bone resorption. Menatetrenone is a useful agent in preventing prednisolone-induced loss of BMD.

Sodium sensitivity of blood pressure appearing before hypertension and related to histological damage in immunoglobulin a nephropathy.

Abstract: Patients with renal parenchymal disease exhibit sodium-sensitive hypertension. We examined patients with immunoglobulin A (IgA) nephropathy to determine whether this sensitivity appears before hypertension begins and whether this sensitivity is related to histological damage. Thirty-eight patients with IgA nephropathy followed a diet with an ordinary sodium level for 1 week and a sodium-restricted diet for 1 week, in random order, and were divided into 3 groups by their systemic blood pressure on the diet with an ordinary sodium level (optimal, <120/<80 mm Hg, n=15; normal to high-normal, 120 to 139/80 to 89 mm Hg, n=18; hypertensive, >/=140/>/=90 mm Hg, n=5). The sodium sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linkage of 2 datum points obtained during the different diets. The scores for glomerulosclerosis and tubulointerstitial damage were evaluated semiquantitatively. The sensitivity index, glomerulosclerosis score, and score for tubulointerstitial damage were higher in patients with normal to high-normal blood pressure or hypertension than in patients with optimal pressure. The sensitivity index was significantly correlated with glomerulosclerosis (P=0.001) and tubulointerstitial damage (P=0.002). In patients with normal to high-normal pressure, sodium restriction lowered blood pressure to the optimal range and decreased proteinuria. In patients with IgA nephropathy, sodium sensitivity of blood pressure related to renal histological damage appears before hypertension.

Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy.

Abstract: Recent studies have shown that steroids improve renal survival and reduce proteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein excretion and normal renal function. However, this effect seems to diminish over time. Moreover, it has been demonstrated that long-term use of ramipril reduces the risk of end-stage renal disease in proteinuric diabetic and non-diabetic chronic nephropathies. We have planned a long-term unblinded, prospective, centrally randomized, controlled, multicentric trial to assess whether combined treatment of steroids and ramipril is superior to ramipril alone in patients with progressive IgAN disease. A minimum of 134 patients with biopsy-proven IgAN, grade G3 or G4, daily proteinuria > 1.0 g and creatinine clearance > 50 mL/min will be enrolled during a 2-year recruitment period. The patients will be allocated randomly to receive a six-month course of oral prednisone (1.0 mg/Kg/day for 2 months, tapered by 0.2 mg/Kg/day every month) plus ramipril (2.5 mg/day for one month, increased by 1.25 mg/day every month to achieve and maintain a blood pressure less than 120-80 mm Hg and/or to reduce daily proteinuria to 1.0 g or less or by at least 50%) in the experimental group or ramipril alone in the control group. Ramipril will be administered during the whole 5-year follow-up period in both groups. The primary endpoint will be renal survival estimated by 50% increase in baseline serum creatinine; the secondary endpoints will be urinary protein and cytokine excretion and side-effects. Analyses will be done by intention to treat. A p <0.05 will be taken as significant.

Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.

Abstract:
Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.

To investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.

Ten non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40-106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.

ACEI and ARB alone reduced proteinuria from 7.9 +/- 7.1 to 5.3 +/- 5.2 and 5.0 +/- 4.9 g/24 h (mean +/- SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 +/- 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 +/- 8; ACEI, 97 +/- 5; ARB, 98 +/- 5; ACEI+ARB, 95 +/- 5 mmHg) or creatinine clearance (basal, 77 +/- 27; ACEI, 73 +/- 31; ARB 80 +/- 30; ACEI + ARB, 73 +/- 32 ml/min).

A combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.

Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies.

Abstract:
Proteinuria predicts renal disease progression, and its reduction by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) is renoprotective.

In this prospective, randomized, cross-over study of 24 patients with nondiabetic, chronic nephropathies, we compared the effects on proteinuria, renal hemodynamics, and glomerular permselectivity of 8 weeks with comparable blood pressure control achieved by benazepril (10 mg/day) and valsartan (80 mg/day) combined therapy with those achieved by benazepril (20 mg/day) or valsartan (160 mg/day) alone.

Despite comparable changes in blood pressure and glomerular filtration rate (GFR), combined therapy decreased proteinuria more than benazepril (-56% vs. -45.9%, P=0.02) and valsartan (-41.5%, P=0.002). Changes in urinary protein to creatinine ratio followed the same trend. Filtration fraction and renal vascular resistances (RVR) decreased more with combined (-14.7%,-23.7%) or benazepril (-12.4%, -20.5%) than with valsartan (-2.7%, -12.5%, P < 0.05 vs. both). RVR changes, adjusted for GFR changes, were associated with those in proteinuria (P < 0.05). Changes in glomerular permeability were comparable and did not predict different changes in proteinuria in the three groups.

At comparable blood pressure, combined ACEi and ARA decreased proteinuria better than ACEi and ARA. The greater antiproteinuric effect most likely depended on an ACEi-related hemodynamic effect, in addition to glomerular size selectivity amelioration. Long-term combined ACEi and ARA therapy may be more renoprotective than treatment with each agent alone.

A comparison of corticosteroid and warfarin therapy in IgA nephropathy with crescent formation: preliminary trial.

Abstract:
No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation.

Fifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months.

Ten of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems (n = 3, warfarin group).

These results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.

A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616].

Abstract:
IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity.

The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF.

After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor, 100 (2 x 50) patients with IgAN and a urinary P/C ratio > or = 0.6 (males) and > or = 0.8 (females) and an estGFR > or = 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two.


Context: Laparoscopic surgery is the preferred option for many procedures. To properly perform laparoscopic surgery, it is essential that sudden movements and abdominal contractions in patients are prevented, as it limits the surgeon's view. There has been a growing interest in the potential beneficial effect of deep neuromuscular blockade (NMB) in laparoscopic surgery. Deep NMB improves the surgical field by preventing abdominal contractions, and it is thought to decrease postoperative pain. However, it is uncertain if deep NMB improves intraoperative safety and thereby improves clinical outcomes.

To evaluate the benefits and harms of deep neuromuscular blockade versus no, shallow, or moderate neuromuscular blockade during laparoscopic intra- or transperitoneal procedures in adults.

We included randomised clinical trials (irrespective of language, blinding, or publication status) in adults undergoing laparoscopic intra- or transperitoneal procedures comparing deep NMB to moderate, shallow, or no NMB. We excluded trials that did not report any of the primary or secondary outcomes of our review.

Evaluation of surgical conditions during laparoscopic surgery in patients with moderate vs deep neuromuscular block.

Abstract:
The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed.

Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1-2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1-2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images.

Mean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1-3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average κ statistic 0.05).

Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients' peri- and postoperative cardiorespiratory conditions. Trial registration The study was registered at clinicaltrials.gov under number NCT01361149.

Deep neuromuscular block improves surgical conditions during laparoscopic hysterectomy: a randomised controlled trial.

Abstract:
The benefit of inducing deep neuromuscular block to improve laparoscopic surgical conditions is controversial.

The goal of this study was to determine the depth of neuromuscular block needed to guarantee excellent operating conditions during laparoscopic hysterectomy.

A randomised controlled trial.

A single-centre study performed between February 2011 and May 2012.

One hundred and two women of ASA physical status 1 or 2 gave consent to participate and were allocated randomly to one of two groups.

Under desflurane general anaesthesia, patients in Group S (shallow block), neuromuscular blockade was induced by administration of rocuronium 0.45 mg  kg-1 followed by spontaneous recovery or a rescue bolus dose of 5  mg if surgical conditions were unacceptable. In Group D (deep block), neuromuscular block was induced by administration of rocuronium 0.6 mg  kg-1 and maintained by bolus doses of 5  mg if the train-of-four count exceeded two, using adductor pollicis electromyography.

With a stable pneumoperitoneum (13 mmHg), the surgeon scored the quality of the surgical field every 10  min as excellent (1), good but not optimal (2), poor but acceptable (3) or unacceptable (4). The groups were compared using the Cochran-Armitage trend test. The level of neuromuscular blockade was recorded each time the surgical field score exceeded 1.

For groups S and D, respectively, the maximum surgical field scores were 1 in 21 and 34 patients, 2 in 11 and 11 patients, 3 in 4 and 5 patients and 4 in 14 and 0 patients. A trend towards higher scores was demonstrated in group S (P < 0.001). Surgical field scores of 2, 3 and 4 occurred only when the train-of-four count was at least 1, 2 and 3, respectively.

Inducing deep neuromuscular block (train-of-four count <1) significantly improved surgical field scores and made it possible to completely prevent unacceptable surgical conditions.

Surgical space conditions during low-pressure laparoscopic cholecystectomy with deep versus moderate neuromuscular blockade: a randomized clinical study.

Abstract:
Laparoscopic cholecystectomy performed during low intraabdominal pressure (<12 mm Hg) is associated with significantly less postoperative pain than standard pressure (≥12 mm Hg). The impact on surgical space conditions and safety of operating at lower pressures has not been adequately described, but deep neuromuscular blockade may be beneficial. We investigated if deep muscle relaxation would be associated with a higher proportion of procedures with "optimal" surgical space conditions compared with moderate relaxation during low-pressure (8 mm Hg) laparoscopic cholecystectomy.

In this assessor-blinded study, 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade (rocuronium bolus plus infusion maintaining a posttetanic count 0-1) or moderate neuromuscular blockade (rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function). Patients received anesthesia with propofol, remifentanil, and rocuronium. The primary outcome was the proportion of procedures with optimal surgical space conditions (assessed by the surgeon as 1 on a 4-point scale). Secondary outcomes included the proportion of procedures completed at pneumoperitoneum 8 mm Hg and surgical space conditions on dissection of the gallbladder (numeric rating scale 0-100; 0 = optimal surgical space conditions; 100 = unacceptable surgical space conditions).

Optimal surgical space conditions during the entire procedure were observed in 7 of 25 patients allocated to deep neuromuscular blockade and in 1 of 23 patients allocated to moderate blockade (P = 0.05) with an absolute difference of 24% between the groups (95% confidence interval, 4%-43%). Laparoscopic cholecystectomy was completed at pneumoperitoneum 8 mm Hg in 15 of 25 and 8 of 23 patients in the deep and moderate group, respectively (95% confidence interval, -2% to 53%; P = 0.08). Surgical space conditions during dissection of the gallbladder assessed by use of the numeric rating scale were 20 (10-50) (median [25%-75% range]) in the deep neuromuscular blockade group and 30 (10-50) in the moderate group (P = 0.58; Wilcoxon-Mann-Whitney odds, 1.2; 95% confidence interval, 0.6-2.5). No operations were converted to laparotomy.

Deep neuromuscular blockade was associated with surgical space conditions that were marginally better than with moderate muscle relaxation during low-pressure laparoscopic cholecystectomy.

Neuromuscular blockade improves surgical conditions (NISCO).

Abstract:
We examined the impact of muscle relaxation on surgical conditions and patients' postoperative outcome during elective laparoscopic cholecystectomy under balanced anaesthesia.

After approval and consent, 57 anaesthetized patients were randomly assigned to group no neuromuscular blockade (No NMB) and deep neuromuscular blockade (Deep NMB), i.e. no twitch response to train-of-four nerve stimulation. Laparoscopic cholecystectomy was performed using the 4-trocar technique with a CO2-pneumoperitoneum. Surgical conditions were assessed using a Visual Analogue Scale. Movement of diaphragm or abdominal muscles, inadequate visibility, or breathing and coughing against the ventilator were documented as events reflecting inadequate muscle relaxation. Independently, surgeons could request 0.3 mg/kg rocuronium to improve surgical conditions. Workflow variables were obtained as a surrogate of surgical conditions. Data are presented as mean (95 % confidence interval). The trial is registered at ClinicalTrials.gov (NCT00895778).

While in 12 of 25 patients of group "No NMB" one or more adverse events impaired the surgical procedure (p < 0.001), only 1 of 25 patients of group "Deep NMB" showed an adverse event. Deep NMB resulted in an absolute risk reduction of 0.44 (0.23-0.65) and a number needed to treat of 2.3 (1.5-4.4), respectively. Surgeons requested 0.3 mg/kg rocuronium in 10 of 25 cases (40 %) of group "No NMB" only. This dose significantly improved surgical conditions by an average 62 of 100 possible points. All further variables did not differ between groups.

Deep NMB ameliorates surgical conditions for laparoscopic cholecystectomy by improved visibility and reduction of involuntary movements.

The Intraocular Pressure under Deep versus Moderate Neuromuscular Blockade during Low-Pressure Robot Assisted Laparoscopic Radical Prostatectomy in a Randomized Trial.

Abstract:
This study aimed to determine whether continuous deep neuromuscular blockade (NMB) improves the surgical conditions and facilitates robotic-assisted laparoscopic radical prostatectomy (RALRP) under low intra-abdominal pressure (IAP) to attenuate the increase in intraocular pressure (IOP) during CO2 pneumoperitoneum in the steep Trendelenburg (ST) position.

Sixty-seven patients undergoing RALRP were randomly assigned to a moderate NMB group (Group M), including patients who received atracurium infusion until the end of the ST position, maintaining a train of four count of 1-2; and the deep NMB group (Group D), including patients who received rocuronium infusion, maintaining a post-tetanic count of 1-2. IOP was measured in all patients at nine separate time points. All RALRPs were performed by one surgeon, who rated the overall and worst surgical conditions at the end of the ST position.

The highest IOP value was observed at T4 (60 min after the ST position) in both Group M (23.3 ± 2.7 mmHg) and Group D (19.8 ± 2.1 mmHg). RALRP was accomplished at an IAP of 8 mmHg in 88% Group D patients and 25% Group M patients. The overall surgical condition grade was 4.0 (3.0-5.0) in Group D and 3.0 (2.0-5.0) in Group M (P < 0.001).

The current study demonstrated that continuous deep NMB may improve surgical conditions and facilitate RALRP at a low IAP, resulting in significant attenuation of the increase on IOP. Moreover, low-pressure pneumoperitoneum, facilitated by deep NMB still provided acceptable surgical conditions.

ClinicalTrials.gov NCT02109133.

No supplemental muscle relaxants are required during propofol and remifentanil total intravenous anesthesia for laparoscopic pelvic surgery.

Abstract:
No administration of supplemental muscle relaxants may be beneficial to the recovery of the ambulatory laparoscopic surgery. For this study, we compared the cardiorespiratory factors during propofol and remifentanil anesthesia for laparoscopic pelvic surgery (LPS) with or without supplemental muscle relaxants.

In total, 56 healthy female patients scheduled to undergo laparoscopic pelvic surgeries were randomly assigned to two groups (A and B). Anesthesia was induced with lidocaine 30 mg, propofol target organ concentration 5.0 microg/mL, remifentanil 3.0 ng/mL, and rocuronium 0.6 mg/kg intravenously (i.v.). After tracheal intubation, anesthesia was maintained with 2.0-5.0 microg/mL of propofol and 1-4 ng/mL of remifentanil i.v. All the patients' lungs were mechanically ventilated in both groups and intermittent bolus doses of rocuronium (0.15 mg/kg i.v.) were administered in group A-however, not in group B. Heart rate (HR) and systolic arterial pressure (SAP), diastolic arterial pressure (DAP), end-tidal carbon-dioxide concentration (EtCO(2)), peak inspiratory pressure (PIP), expired minute ventilation (MV), intra-abdominal pressure (IAP), and temperature were measured during the pneumoperitoneum.

There were no group differences in HR, SAP, DAP, EtCO(2), PIP, IAP, MV, PaO(2), PaCO(2), and temperature between groups A and B.

No supplemental muscle relaxants are required during propofol and remifentanil total i.v. anesthesia for LPS.

Deep neuromuscular block reduces intra-abdominal pressure requirements during laparoscopic cholecystectomy: a prospective observational study.

Abstract:
Laparoscopic surgery causes specific post-operative discomfort and intraoperative cardiovascular, pulmonary, and splanchnic changes. The CO2 pneumoperitoneum-related intra-abdominal pressure (IAP) remains one of the main drivers of these changes. We investigated the influence of deep neuromuscular blockade (NMB) on IAP and surgical conditions.

This is an open prospective single-subject design study in 20 patients (14 female/6 male) undergoing laparoscopic cholecystectomy. Inclusion criteria were 18 years or older, and American Society of Anesthesiologists classification 1 to 3. Under a standardised anaesthesia, lowest IAP providing adequate surgical conditions was assessed without NMB and with deep NMB [post-tetanic count (PTC)<2] with rocuronium. The differences between IAP allowing for an adequate surgical field before and after administration of rocuronium were determined, as were effects of patient gender, age, and body mass index.

Mean IAP without NMB was 12.75 (standard deviation 4.49) mmHg. Immediately after achieving a deep NMB, this was 7.20 (2.51). This pressure difference of 5.55 mmHg (5.08, P<0.001) dropped to 3.00 mmHg (4.30, P<0.01) after 15 min. Higher IAP differences were found in women compared with men. A modest inverse relationship was found between pressure difference and age.

We found an almost 25% lower IAP after a deep NMB compared with no block in laparoscopic cholecystectomy. Younger and female patients appear to benefit more from deep neuromuscular blockade to reduce IAP.

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

Abstract: Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

Optimising abdominal space with deep neuromuscular blockade in gynaecologic laparoscopy--a randomised, blinded crossover study.

Abstract:
Insufflation of the abdomen during laparoscopy improves surgical space, but may cause post-operative shoulder pain. The incidence of shoulder pain is reduced using a lower insufflation pressure, but this may, however, compromise the surgical space. We aimed at investigating whether deep neuromuscular blockade (NMB) would enlarge surgical space, measured as the distance from the sacral promontory to the trocar in patients undergoing gynaecologic laparoscopy.

Fourteen patients were randomised in an assessor-blinded crossover design. The distance from the sacral promontory to the trocar was measured during deep NMB and without NMB at pneumoperitoneum 8 and 12 mmHg both. Additionally, we assessed surgical conditions while suturing the abdominal fascia using a 4-point subjective rating scale. Deep NMB was established with rocuronium and reversed with sugammadex.

At 12 mmHg pneumoperitoneum, deep NMB improved surgical space with a mean of 0.33 cm (95% confidence interval 0.07-0.59) (P=0.01, paired t-test) compared with no NMB. At 8 mmHg pneumoperitoneum deep NMB improved surgical space with a mean of 0.3 cm (95% confidence interval, 0.06-0.54) (P=0.005) compared with no NMB. Deep NMB resulted in significantly better ratings of surgical conditions during suturing of the fascia (P=0.03, Mann-Whitney U-test).

Deep NMB enlarged surgical space measured as the distance from the sacral promontory to the trocar. The enlargement, however, was minor and the clinical significance is unknown. Moreover, deep NMB improved surgical conditions when suturing the abdominal fascia.

Neuromuscular blockade during laparoscopic ventral herniotomy: protocol for a randomised controlled trial.

Abstract:
Laparoscopic herniotomy is the preferred technique for some ventral hernias. Several factors may influence the surgical conditions, one being the depth of neuromuscular blockade (NMB) applied. We hypothesised that deep neuromuscular blockade defined as a post-tetanic count below eight would provide a better surgical workspace.

This was an investigator-initiated, assessor- and patient-blinded randomised cross-over study. A total of 34 patients with planned laparoscopic umbilical, incisional and linea alba herniotomy were studied. Patients would be randomised to receive deep NMB followed by no NMB, or no NMB followed by deep NMB. Our primary outcome was improvement of the surgical workspace (rated on a five-point scale) estimated as the difference between the workspace during deep NMB and the workspace without NMB. Secondary outcomes included, among others, surgeon's rating of surgical conditions during suturing, duration of surgery and duration of the suturing of the hernia.

This randomised cross-over study investigated a potential effect on the surgical workspace in laparoscopic ventral herniotomy using deep NMB compared with no NMB. The study may provide knowledge relevant to other laparoscopic techniques.

The study is funded by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp.

NCT02247466.


Context: Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017.

To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach.

We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention.

A randomized controlled trial of shared decision making for prostate cancer screening.

Abstract:
To evaluate a patient-educational approach to shared decision making for prostate cancer screening.

Randomized controlled trial with preoffice visit assessment and 2-week follow-up.

University-based family practice center.

Men aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease (N = 160). Two patients were unavailable for follow-up.

Twenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen (PSA) screening for prostate cancer.

A measure of patients' core knowledge of prostate cancer developed for this study, reported preferences for PSA testing, and ratings of the videotape.

Patients' core knowledge at baseline was poor. At 2-week follow-up, subjects undergoing videotape intervention showed a 78% improvement in the number of knowledge questions answered correctly (P = .001), and knowledge increased about mortality due to early-stage prostate cancer, PSA screening performance, treatment-related complications, and disadvantages of screening. No overall change was observed for control subjects. At follow-up, 48 (62%) of 78 intervention patients planned to have the PSA test compared with 64 (80%) of 80 control patients (18.5% absolute reduction; 95% confidence interval, 4.6%-32.4%; P = .009). Intervention subjects rated favorably the amount of information provided and the clarity, balance, and length of the videotape and would recommend the videotape to others.

Patient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making. Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended.

A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.

Abstract:
Decision aids are tools designed to help patients participate in the clinical decision-making process.

To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants.

Randomized controlled trial conducted from May 1997 to April 1998.

Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial.

A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years.

At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin.

Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured.

More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44).

For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.

Does informed consent alter elderly patients' preferences for colorectal cancer screening? Results of a randomized trial.

Abstract:
To assess the impact of informed consent on elderly patients' colorectal cancer (CRC) screening preferences.

Randomized, controlled trial.

Four general internal medicine practices.

We studied 399 elderly patients visiting their primary care provider for routine office visits.

Patients were randomized to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening. One intervention described CRC mortality risk reduction in relative terms; the other, in absolute terms.

The main outcome measure was intent to begin or continue fecal occult blood testing (FOBT), flexible sigmoidoscopy, or both. There was no difference in screening interest between the control group and the two information groups (p =.8). The majority (63%) of patients intended to begin or continue CRC screening. Informed patients were able to gauge more accurately the positive predictive value of screening (p =.0009). Control patients rated the efficacy of screening higher than did patients receiving relative risk reduction information, who rated it higher than did patients receiving absolute risk reduction information (p =.0002).

Elderly patients appeared to understand CRC screening information and use it to gauge the efficacy of screening, but provision of information had no impact on their preferences for screening. In view of the large proportion who preferred not to be screened, we conclude that elderly patients should be involved in the screening decision. However, factors other than provision of information must determine their CRC screening preferences.

Videotape-based decision aid for colon cancer screening. A randomized, controlled trial.

Abstract:
Rates of colon cancer screening in the United States are low, in part because of poor communication between patients and providers about the availability of effective screening options.

To test whether a decision aid consisting of an educational video, targeted brochure, and chart marker increased performance of colon cancer screening in primary care practices.

Randomized, controlled trial.

Three community primary care practices in central North Carolina.

1657 consecutive adult patients 50 to 75 years of age were contacted. Of these, 651 (39%) agreed to participate; 249 of the 651 participants (38%) were eligible. Eligible patients had no personal or family history of colon cancer and had not had fecal occult blood testing in the past year or flexible sigmoidoscopy, colonoscopy, or barium enema in the past 5 years.

The 249 participants were randomly assigned to view an 11-minute video about colon cancer screening (intervention group) or a video about automobile safety (control group). After viewing the video, intervention group participants chose a color-coded educational brochure (based on stages of change) to indicate their degree of interest in screening. A chart marker of the same color was attached to their charts. Controls received a generic brochure on automobile safety, and no chart marker was attached.

Frequency of screening test ordering as reported by participants and frequency of completion of screening tests as verified by chart review.

Fecal occult blood testing or flexible sigmoidoscopy was ordered for 47.2% of intervention participants and 26.4% of controls (difference, 20.8 percentage points [95% CI, 8.6 to 32.9 percentage points]). Screening tests were completed by 36.8% of the intervention group and 22.6% of the control group (difference, 14.2 percentage points [CI, 3.0 to 25.4 percentage points]).

A decision aid consisting of an educational video, brochure, and chart marker increased ordering and performance of colon cancer screening tests.

Randomized, controlled trial of an interactive videodisc decision aid for patients with ischemic heart disease.

Abstract:
To determine the effect of the Ischemic Heart Disease Shared Decision-Making Program (IHD SDP) an interactive videodisc designed to assist patients in the decision-making process involving treatment choices for ischemic heart disease, on patient decision-making.

Randomized, controlled trial.

The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.

Two hundred forty ambulatory patients with

The primary outcome was patient satisfaction with the decision-making process. This was measured using the 12-item Decision-Making Process Questionnaire that was developed and validated in a randomized trial of the benign prostatic hyperplasia SDP. Secondary outcomes included patient knowledge (measured using 20 questions about knowledge deemed necessary for an informed treatment decision), treatment decision, patient-angiographer agreement on decision, and general health scores. Outcomes were measured at the time of treatment decision and/or at 6 months follow-up. Shared decision-making program scores were similar for the intervention and control group (71% and 70%, respectively; 95% confidence interval [CI] for 1% difference, -3% to 7%). The intervention group had higher knowledge scores (75% vs 62%; 95% CI for 13% difference, 8% to 18%). The intervention group chose to pursue revascularization less often (58% vs 75% for the controls; 95% CI for 17% difference, 4% to 31%). At 6 months, 52% of the intervention group and 66% of the controls had undergone revascularization (95% CI for 14% difference, 0% to 28%). General health and angina scores were not different between the groups at 6 months. Exposure to the IHD SDP resulted in more patient-angiographer disagreement about treatment decisions.

There was no significant difference in satisfaction with decision-making process scores between the IHD SDP and usual practice groups. The IHD SDP patients were more knowledgeable, underwent less revascularization (interventional therapies), and demonstrated increased patient decision-making autonomy without apparent impact on quality of life.

A randomized controlled trial of information-giving to patients referred for coronary angiography: effects on outcomes of care.

Abstract: OBJECTIVE: To assess the impact of providing an educational videotape, 'Treatment Choices for Ischaemic Heart Disease: a Shared Decision-Making Program Videotape,' to patients referred for coronary angiography compared with standard patient-physician decision making (usual care). STUDY DESIGN: Randomized controlled clinical trial. SETTING: University Hospital and Veterans Affairs Hospital. PATIENTS: A consecutive sample of 217 patients referred for coronary angiography were randomized to receive 'usual care' or to receive the videotape in addition to standard patient physician decision making (videotape): 109 completed the study (50% completion rate). MAIN OUTCOME MEASURES: Knowledge of coronary artery disease, satisfaction, self-reported physical and mental health functioning, and the proportion of patients who were referred for coronary revascularization. RESULTS: Compared with patients who received 'usual care,' those who received the videotape were more knowledgeable (mean score 83 vs. 58%; P < 0.0001) but less satisfied with their treatment (79 vs. 88%; P = 0.038). There were no significant differences between the videotape and 'usual care' groups with respect to satisfaction with the decision making process (mean score 73 vs. 77%; P = 0.37), satisfaction with the decision made (mean score 73 vs. 78%; P = 0.28), physical functioning (38 vs. 38%; P = 0.76), mental health functioning (49 vs. 49%; P = 0.94), or in referral for coronary revascularization (OR 0.60; 95% CI 0.22-1.65; P = 0.33). CONCLUSION: Although the educational videotape increased patients' knowledge level, it was associated with a decrease in their level of satisfaction with treatment. Before there is wide-spread dissemination of this technology, advocates should demonstrate its effectiveness in everyday practice.

Randomised controlled trial of an interactive multimedia decision aid on hormone replacement therapy in primary care.

Abstract:
To determine whether a decision aid on hormone replacement therapy influences decision making and health outcomes.

Randomised controlled trial.

26 general practices in the United Kingdom.

205 women considering hormone replacement therapy.

Patients' decision aid consisting of an interactive multimedia programme with booklet and printed summary.

Patients' and general practitioners' perceptions of who made the decision, decisional conflict, treatment choice, menopausal symptoms, costs, anxiety, and general health status.

Both patients and general practitioners found the decision aid acceptable. At three months, mean scores for decisional conflict were significantly lower in the intervention group than in the control group (2.5 v 2.8; mean difference -0.3, 95% confidence interval -0.5 to -0.2); this difference was maintained during follow up. A higher proportion of general practitioners perceived that treatment decisions had been made "mainly or only" by the patient in the intervention group than in the control group (55% v 31%; 24%, 8% to 40%). At three months a lower proportion of women in the intervention group than in the control group were undecided about treatment (14% v 26%; -12%, -23% to -0.4%), and a higher proportion had decided against hormone replacement therapy (46% v 32%; 14%, 1% to 28%); these differences were no longer apparent by nine months. No differences were found between the groups for anxiety, use of health service resources, general health status, or utility. The higher costs of the intervention were largely due to the video disc technology used.

An interactive multimedia decision aid in the NHS would be popular with patients, reduce decisional conflict, and let patients play a more active part in decision making without increasing anxiety. The use of web based technology would reduce the cost of the intervention.

Patient decision support intervention: increased consistency with decision analytic models.

Abstract:
Patient Decision Support (PDS) tools assist patients in using medical evidence to make choices consistent that are with their values and in using evidence about consequences of medical alternatives.

To evaluate a PDS intervention for perimenopausal hormone replacement therapy. We assessed the impact of the PDS on (1) consistency between the decision to take estrogen replacement therapy (ERT) or progesterone/estrogen replacement therapy (PERT) and the expected utility of treatment and (2) likelihood to take ERT and PERT pre- and postintervention.

Content of the PDS was standardized. Randomized trial of three intensities of intervention: (1) brochure; (2) lecture/discussion; and (3) active decision support.

Participants were perimenopausal community volunteers between the ages of 40 and 65 (n = 248).

(1) Consistent with values (correlation between expected utility (EU) and likelihood of taking hormones); and (2) Likelihood to take hormone replacement therapy.

(1) The brochure group was less consistent with the decision analytic model than the lecture/discussion and active decision support groups. (2) Influence on decisions: PDS tools increased the number of women certain about whether or not to take hormones. There were no differences among experimental groups. Of 99 women uncertain about ERT pre-PDS, 65% changed. Twenty-one (32%) decided against ERT and 44 (68%) decided for ERT. (3) More intensive interventions produced modest gains in a normative direction.

PDSs using any of 3 formats reduce uncertainty and assist women to make informed decisions. Increased consistency with decision analytic models appears to be driven by better estimates of likelihood of outcomes.

Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.

Abstract:
To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests.

Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only).

Antenatal clinic in university teaching hospital.

875 women booking antenatal care.

All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic.

Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety.

All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001).

The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.

Effects of ZDV-based patient education on intentions toward ZDV use, HIV testing and reproduction among a US cohort of women.

Abstract: This study examined the immediate effects of exposure to a patient education brochure concerning the risks and benefits of zidovudine (ZDV) therapy during pregnancy to reduce perinatal HIV transmission (protocol ACTG 076) on related knowledge, behavioural intentions and attitudes of women with and at-risk for HIV-infection. Self-reports were collected from 653 women of childbearing age from community family planning clinics and hospital-based HIV centres in 19 sites from nine US cities between May and November 1995. The intervention was a nine-page patient education brochure in Spanish, Creole and English versions, evently presenting the pros and cons of ZDV therapy to reduce perinatal HIV-transmission. Brochure exposure increased knowledge (p < 0.001) for all but one scale concerning ZDV resistance and increased the likelihood of women reporting intentions to take ZDV during pregnancy (p < 0.001) and to believe ZDV reduced transmission (p < 0.001). Brochure exposure had differential effects for some subpopulations. Intentions to have or terminate current or future pregnancies, knowledge about ZDV and attitudes toward ZDV varied mostly by ethnicity/race, language preference and HIV status. Pregnancy status, age, education and having an HIV-positive child had less impact on the brochure's effect, while income had no impact.