Context: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections.

To assess the effectiveness of cranberries for the treatment of UTIs.

All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included.

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? Protocol for a feasibility study.

Abstract:
Consultations in primary care for symptoms of urinary tract infections (UTIs) are common and patients are frequently treated with antibiotics. Given increasing antimicrobial resistance, there has been interest in non-antibiotic treatment options for common infections. One such option is the use of cranberry extract to treat symptoms attributable to UTIs.

A target of 45 women consulting in primary care, with symptoms suggestive of an uncomplicated UTI for whom the practitioner would normally prescribe antibiotics, will be randomised to receive one of three treatment approaches: (1) immediate prescription for antibiotics; (2) immediate prescription for antibiotics plus a 7-day course of cranberry capsules and (3) cranberry capsules plus a delayed prescription for antibiotics to be used in case their symptoms do not get better, or get worse. Follow-up will be by daily rating of symptoms and recording of treatments used for 2 weeks in an online symptom diary. Interviews will be conducted with around 10-15 study participants, as well as with around 10-15 women who have experienced a UTI but have not been approached to take part in the study. Both groups will be asked about their experience of having a UTI, their thoughts on non-antibiotic treatments for UTIs and their thoughts on, or experience of, the feasibility trial. The primary objective is to assess the feasibility of undertaking a full trial in primary care of the effectiveness of cranberry extract to reduce antibiotic use for symptoms of acute uncomplicated UTI. The secondary objective is to conduct a preliminary assessment of the extent to which cranberry might reduce antibiotic use and symptom burden.

This feasibility study with embedded interviews will inform the planning and sample size calculation of an adequately powered trial to definitively determine whether cranberry helps to alleviate the symptoms of acute uncomplicated UTIs in women and whether it can safely reduce antibiotic use.

ISRCTN registry, ID: 10399299. Registered on 24 January 2019.

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? A feasibility randomised trial.

Abstract:
To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI).

Open-label feasibility randomised parallel group trial.

Four general practices in Oxfordshire.

Women aged 18 years and above presenting to general practice with symptoms of acute, uncomplicated UTI.

Women were randomly assigned using Research Electronic Data Capture in a 1:1:1 ratio to: (1) immediate antibiotics alone (n=15); (2) immediate antibiotics and immediate cranberry capsules for up to 7 days (n=15); or (3) immediate cranberry capsules and delayed antibiotics for self-initiation in case of non-improvement or worsening of symptoms (n=16).

The primary outcome measures were: rate of recruitment of participants; numbers lost to follow-up; proportion of electronic diaries completed by participants; and acceptability of the intervention and study procedures to participants and recruiters. Secondary outcomes included an exploration of differences in symptom burden and antibiotic use between groups.

Four general practitioner practices (100%) were opened and recruited participants between 1 July and 2 December 2019, with nine study participants recruited per month on average. 68.7% (46/67) of eligible participants were randomised (target 45) with a mean age of 48.4 years (SD 19.9, range 18-81). 89.1% (41/46) of diaries contained some participant entered data and 69.6% (32/46) were fully complete. Three participants (6.5%) were lost to follow-up and two (4.4%) withdrew. Of women randomly assigned to take antibiotics alone (controls), one-third of respondents reported consuming cranberry products (33.3%, 4/12). There were no serious adverse events.

It appears feasible to conduct a randomised trial of the use of cranberry extract in the treatment of acute, uncomplicated UTI in general practice.

ISRCTN Registry (ID: 10399299).

Prevention and treatment of cystitis during menopause: efficacy of a nutraceutical containing D-mannose, inulin, cranberry, bearberry,

Abstract:
To evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry,

This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS).

At 6 months of therapy, the reduction in the number of patients with ≥ 2 UTIs was statistically significant (

In menopausal women, the combination of D-mannose, inulin, cranberry, bearberry,

Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy.

Abstract: Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.

Predictability of methenamine efficacy based on type of urinary pathogen and pH.

Abstract: This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.

Lack of effect of ascorbic acid, hippuric acid, and methenamine (urinary formaldehyde) on the copper-reduction glucose test in geriatric patients.

Abstract: Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.

Combination of cranberry extract and D-mannose - possible enhancer of uropathogen sensitivity to antibiotics in acute therapy of urinary tract infections: Results of a pilot study.

Abstract: Uncomplicated lower urinary tract infections are extremely common in women. Antibiotic treatment for acute episodes and for recurrence prophylaxis has its drawbacks and alternative therapies are sought in order to reduce the antimicrobial resistance phenomenon and the intestinal dismicrobism expansion. There are few studies on the effect of combination of cranberry extract with D-mannose in acute urinary tract infection management. In a pilot, randomized study 93 non-pregnant, otherwise healthy women, were enrolled with mean age of 39.77±10.36, diagnosed with uncomplicated lower urinary tract infection. Medical history, clinical examination, urine culture and a list of complaints were noted at the baseline visit. In a first phase of the study, treatment with either guideline recommended antibiotic alone or in association with the investigated product (cranberry extract plus D-mannose) was prescribed and all patients were clinically examined at day 7. All ameliorated and cured patients received in a second phase of the study, in a double-blind manner, prophylaxis with the investigated product or placebo for another 21 days, then a second clinical examination and a check of the list of complaints were performed. The cure rates were higher at day 7 when investigated product was added to antibiotic (91.6 vs. 84.4%). In resistant strains, a significantly higher cure rate was shown when the investigated product was added to antibiotic prescribed (88.8 vs. 37.5%, P<0.0001). The effect of cranberry extract plus D-mannose combination in acute urinary tract infection episodes seems to be promising. The significant cure rate registered in the patients with antibiotic-resistant urine cultures may be explained by a beneficial influence of the product on the antimicrobial sensitivity. Further studies are needed on this subject.

Clinical evaluation of herbal coded formulation Cran-off to Urixin in the treatment of urinary tract infection.

Abstract: Urinary Tract Infections are the largest group of infections after the respiratory tract infections. In 85% of the cases the causative organism is E. Coli. A clinical trial was conducted to evaluate the efficacy of coded herbal formulation "Cranoff" (Test drug) for the treatment of Urinary tract infection comparing with Urixin (Control). One hundred and thirty patients suffering from Urinary tract infection from both groups (Males: 45, mean age: 34±14 and females: 85, mean age: 33±13 year, range: 15-55) were enrolled in the trial and divided in to two groups according to treatment regimens. Cranoff (Test drug) 500mg two capsules and Urixin (Pipemidic Acid Trihydrate JP15) (Control) 400mg capsules twice daily were prescribed for 2-3 weeks. Urinary tract infection was improved in 23 (35.38%) patients out of 65 patients by the use of Cranoff (Test drug), and in 15 (23.07%) patients out of 65 by the use of Urixin (Control drug). Furthermore, there was a significant improvement in Urinary tract infection associated clinical features as compared to Urixin. It is concluded that Cranoff possesses a therapeutic value for the improvement of urinary tract infection and its associated symptoms as compared to Urixin.


Context: Many people receiving palliative care have reduced oral intake during their illness, and particularly at the end of their life. Management of this can include the provision of medically assisted hydration (MAH) with the aim of improving their quality of life (QoL), prolonging their life, or both. This is an updated version of the original Cochrane Review published in Issue 2, 2008, and updated in February 2011 and March 2014.

To determine the effectiveness of MAH compared with placebo and standard care, in adults receiving palliative care on their QoL and survival, and to assess for potential adverse events.

We included all relevant randomised controlled trials (RCTs) of studies of MAH in adults receiving palliative care aged 18 and above. The criteria for inclusion was the comparison of MAH to placebo or standard care.

Effects of parenteral hydration in terminally ill cancer patients: a preliminary study.

Abstract:
Most patients with cancer develop decreased oral intake and dehydration before death. This study aimed to determine the effect of parenteral hydration on overall symptom control in terminally ill cancer patients with dehydration.

Patients with clinical evidence of mild to moderate dehydration and a liquid oral intake less than 1,000 mL/day were randomly assigned to receive either parenteral hydration with 1,000 mL (treatment group) or placebo with 100 mL normal saline administered over 4 hours for 2 days. Patients were evaluated for target symptoms (hallucinations, myoclonus, fatigue, and sedation), global well-being, and overall benefit.

Twenty-seven patients randomly assigned to the treatment group had improvement in 53 (73%) of their 73 target symptoms versus 33 (49%) of 67 target symptoms in the placebo group (n=22; P = .005). Fifteen (83%) of 18 and 15 (83%) of 18 patients had improved myoclonus and sedation after hydration versus eight (47%) of 17 and five (33%) of 15 patients after placebo (P = .035 and P = .005, respectively). There were no significant differences of improvement in hallucinations or fatigue between groups. When blinded to treatment, patients (17 [63%] of 77) and investigators (20 [74%] of 27) perceived hydration as effective compared with placebo in nine (41%) of 22 patients (P = .78) and 12 (54%) of 22 investigators (P = .15), respectively. The intensity of pain and swelling at the injection site were not significantly different between groups.

Parenteral hydration decreased symptoms of dehydration in terminally ill cancer patients who had decreased fluid intake. Hydration was well tolerated, and a placebo effect was observed. Studies with larger samples and a longer follow-up period are justified.

Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.

Abstract:
The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.

We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups.

The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83).

Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.

Hypodermoclysis for control of dehydration in terminal-stage cancer.

Abstract: Many of those involved in palliative care have justifiable objections to the introduction of intravenous hydration in patients with dehydration-associated symptoms and advanced cancer. Researchers from the University of Buenos Aires carried out a randomized, comparative and prospective trail to determine the usefulness of hypodermoclysis in the control of thirst, chronic nausea and delirium. Forty-two patients were randomized into two groups. Both groups received drugs subcutaneously (haloperidol 2.5 mg every 4 hours to control delirium and/or metoclopramide 10 mg every 4 hours to control chronic nausea). The study group also received 1000 ml 5% dextrose in water infusion plus 140 milliequivalent per litre (mEq/L) sodium chloride, at a rate of 42 ml/hour per day. Both groups showed significant and equal improvements in relief of thirst and chronic nausea at 24 hours. After 48 hours, this improvement was maintained in the group that received hydration, but only for the relief of chronic nausea. Delirium did not improve significantly in either group during the 48-hour trial period. Current data suggest that decisions on rehydration of patients with terminal-phase cancer should be based more on the patient's comfort than on providing optimal hydration.

A cluster randomised feasibility trial of clinically assisted hydration in cancer patients in the last days of life.

Abstract:
The provision of clinically assisted hydration at the end-of-life is one of the most contentious issues in medicine.

The aim of this feasibility study was to answer the question 'can a definitive (adequately powered) study be done?'

The study was a cluster randomised trial, with sites randomised on a one-to-one basis to intervention 'A' (regular mouth care and usual other care) or intervention 'B' (clinically assisted hydration, mouth care and usual other care). Participants were assessed every 4 h, and data collected on clinical problems, therapeutic interventions and overall survival.

The study was conducted at 12 sites/'clusters' with specialist palliative care teams (4 cancer centres and 8 hospices), and participants were cancer patients in the last week of life who were unable to maintain sufficient oral fluid intake.

The study achieved its pre-determined criteria for success. Two hundred patients were recruited to the study, and 199 participants completed the study, over a 1-year period. A total of 38.5% participants discontinued clinically assisted hydration due to adverse effects: none of these adverse events were rated as 'severe' or worse in intensity. The primary reasons for discontinuation were site problems ( n = 2), localised oedema ( n = 13), generalised oedema ( n = 5), respiratory secretions ( n = 6) and nausea and vomiting ( n = 1).

The results of this feasibility study suggest that a definitive study can be done, but that minor changes are needed to the protocol to standardise the administration of clinically assisted hydration (which may reduce the incidence of certain adverse effects).

Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational study.

Abstract: Although the dehydration-rehydration problem in end-of-life care is one of the most important issues, clinical indications of hydration therapy have not been clarified because the pathophysiology is poorly understood. To explore the physiological changes of fluid status in terminally ill cancer patients, a prospective observational study was performed. We obtained 9 pairs of blood samplings from hospice inpatients with irreversible bowel obstruction who underwent two or more laboratory examinations during the admission periods. The plasma renin activity (PRA) and brain natriuretic peptide (BNP) were measured, in addition to basic laboratory tests performed as clinically required. A chart review evaluated the degree of fluid retention symptoms. In 7 patients receiving intravenous rehydration of 700-2200 ml/day, the mean PRA level significantly increased from 3.5+/-2.5 ng ml(-1) h(-1) to 11+/-8.2 ng ml(-1) x h(-1) ( P=0.047), and the mean BNP level significantly decreased from 52+/-34 pg/ml to 22+/-14 pg/ml ( P=0.047). Edema, ascites, and pleural effusion/pulmonary edema deteriorated in 5, 3, and 5 patients, respectively. In 2 patients without rehydration therapy, peripheral edema deteriorated with increased PRA levels (0.5 to 20 ng ml(-1) x h(-1), 0.4 to 8.7 ng ml(-1) x h(-1), respectively). In conclusion, intravenous volume depletion with fluid retention symptoms was observed in terminally ill cancer patients with intestinal obstruction both receiving and not receiving intravenous hydration. The pathological mechanism hypothesized is the fluid shift from the intravascular compartment to the interstitial spaces.

Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies.

Abstract:
To explore the association between hydration volume and symptoms during the last 3 weeks of life in terminally ill cancer patients.

This was a multicenter, prospective, observational study of 226 consecutive terminally ill patients with abdominal malignancies. Primary responsible physicians and nurses evaluated the severity of membranous dehydration (dehydration score calculated from three physical findings), peripheral edema (edema score calculated from seven physical findings), ascites and pleural effusion (rated as physically undetectable to symptomatic), bronchial secretion, hyperactive delirium (Memorial Delirium Assessment Scale), communication capacity (Communication Capacity Scale), agitation (Agitation Distress Scale), myoclonus and bedsores.

Patients were classified into two groups: the hydration group (n=59) who received 1 l or more of artificial hydration per day, 1 and 3 weeks before death, and the non-hydration group (n=167). The percentage of patients with deterioration in dehydration score in the final 3 weeks was significantly higher in the non-hydration group than the hydration group (35% versus 14%; P=0.002), while the percentages of patients whose symptom scores for edema, ascites and pleural effusion increased were significantly higher in the hydration group than the non-hydration group (44% versus 29%, P=0.039; 29% versus 8.4%, P <0.001; 15% versus 5.4%, P=0.016; respectively). After controlling for multiple covariates and treatment settings, the association between hydration group and dehydration/ascites score was statistically significant. Subgroup analysis of patients with peritoneal metastases identified statistically significant interaction between hydration group and dehydration/pleural effusion score. There were no significant differences in the degree of bronchial secretion, hyperactive delirium, communication capacity, agitation, myoclonus or bedsores.

Artificial hydration therapy could alleviate membranous dehydration signs, but could worsen peripheral edema, ascites and pleural effusions. It is suggested that the potential benefits of artificial hydration therapy should be balanced with the risk of worsening fluid retention symptoms. Further clinical studies are strongly needed to identify the effects of artificial hydration therapy on overall patient well-being, and an individualized treatment and close monitoring of dehydration and fluid retention symptoms is strongly recommended.

Artificial hydration therapy, laboratory findings, and fluid balance in terminally ill patients with abdominal malignancies.

Abstract: To explore the association between hydration volume and laboratory findings, and between calculated fluid balance and changes in clinical signs of dehydration and fluid retention in terminally ill cancer patients, a secondary analysis of a large multicenter, prospective, observational study was performed. The study enrolled 125 abdominal cancer patients who received laboratory examinations in the last week before death. Patients were classified into two groups: the hydration group (n = 44), who received 1L or more of artificial hydration per day both 1 and 3 weeks before death, and the nonhydration group (n = 81). The mean albumin level 1 week before death was significantly lower in the hydration group than in the nonhydration group, and the interaction between hydration group and decrease in the albumin level was statistically significant after adjusting multiple covariates (from 2.8 +/- 0.68 mg/dL 3 weeks before death to 2.4 +/- 0.56 mg/dL 24 hours before death in the hydration group vs. a decrease of 2.8 +/- 0.53 to 2.6+ /- 0.45 mg/dL in the nonhydration group, P = 0.015). There was no significant difference between the groups in the mean blood urea nitrogen/creatinine, sodium, or potassium levels 1 week before death. Among 53 patients who had oral fluid intake of less than 500 mL/day throughout the last 3 weeks and completed a fluid balance study, the median of calculated fluid balance was -400 mL/day 3 weeks before death, -521 mL/day 1 week before death, and -421 mL/day 24 hours before death. Calculated fluid balances did not significantly differ between the patients with deterioration of dehydration signs, edema, ascites, and pleural effusion during the final 3 weeks and those without. These data suggest that active artificial hydration might result in hypoalbuminemia, with no clear beneficial effects on normalizing blood urea nitrogen/creatinine, sodium, or potassium levels. Fluid balance did not significantly correlate with changes in dehydration-and fluid retention-signs. Calculated fluid balance is not an appropriate alternative to direct monitoring of patient symptoms. More studies are needed to determine the clinical efficacy of artificial hydration for terminally ill cancer patients.

Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.

Abstract:
Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed.

Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer.

This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death.

The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7).

Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.

Hydration in advanced cancer: can bioelectrical impedance analysis improve the evidence base? A systematic review of the literature.

Abstract:
Decisions surrounding the administration of clinically assisted hydration to patients dying of cancer can be challenging because of the limited understanding of hydration in advanced cancer and a lack of evidence to guide health care professionals. Bioelectrical impedance analysis (BIA) has been used to assess hydration in various patient groupings, but evidence for its use in advanced cancer is limited.

To critically appraise existing methods of hydration status assessment in advanced cancer and review the potential for BIA to assess hydration in advanced cancer.

Searches were carried out in four electronic databases. A hand search of selected peer-reviewed journals and conference abstracts also was conducted. Studies reporting (de)hydration assessment (physical examination, biochemical measures, symptom assessment, and BIA) in patients with advanced cancer were included.

The results highlight how clinical examination and biochemical tests are standard methods of assessing hydration, but limitations exist with these methods in advanced cancer. Furthermore, there is disagreement over the evidence for some commonly associated symptoms with dehydration in cancer. Although there are limitations with using BIA alone to assess hydration in advanced cancer, analysis of BIA raw measurements through the method of bioelectrical impedance vector analysis may have a role in this population.

The benefits and burdens of providing clinically assisted hydration to patients dying of cancer are unclear. Bioelectrical impedance vector analysis shows promise as a hydration assessment tool but requires further study in advanced cancer. Innovative methodologies for research are required to add to the evidence base and ultimately improve the care for the dying.


Context: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear.

To assess the effects (benefits and harms) of topical and oral steroids for OME in children.

We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared topical or oral steroids with either placebo or watchful waiting (no treatment).

[The efficacy of combining antibiotic treatment with topical intranasal steroid administration in the treatment of chronic otitis media with effusion].

Abstract:
We evaluated the efficacy of antibiotic treatment with or without topical administration of intranasal budesonide in chronic otitis media with effusion (OME).

The study included 62 patients (age range 2 to 12 years) with chronic OME. The patients were randomly assigned to three groups, namely, antibiotic treatment (20 patients, ampicillin/sulbactam, 25 mg/kg/daily), antibiotic treatment combined with intranasal budesonide (20 patients, 200 mg/daily), and no treatment (22 patients). All patients and families were questioned regarding the presence of allergy, frequent upper respiratory tract infections, passive smoking, low birth weight, and pre-school nursery attendance. Otoscopic examination findings and the results of tympanograms obtained at the time of diagnosis, and at the end of four and eight weeks of treatment were evaluated.

At the end of eight weeks, significant improvement in tympanograms and otoscopic findings was obtained in both groups when compared with the control group (p<0.05). Resolution rates were 24% (9/37 ears), 39% (14/36), and 5% (2/40) with antibiotic, budesonide, and no treatment groups, respectively. Although budesonide treatment was associated with a higher rate of resolution of effusion compared to that of antibiotic alone, this did not reach significance (p>0.05).

Further studies with larger patient series are required to better evaluate the efficacy of antibiotic treatment and topical intranasal steroid administration in chronic OME.

Systemic steroid for chronic otitis media with effusion in children.

Abstract:
To determine the efficacy of a short course of an adrenocorticosteroid agent (prednisolone) given with amoxicillin as compared with that of amoxicillin alone for the treatment of chronic middle ear effusion (MEE). The efficacy of 2 weeks versus 4 weeks of amoxicillin with and without steroid was also assessed.

In a double-blind, randomized trial, children who were 1 to 9 years of age and had MEE of at least 2 months' duration were assigned to 1 of 4 treatment arms: 1) steroid + amoxicillin for 14 days, then amoxicillin for 14 more days; 2) steroid + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days; 3) placebo (for steroid) + amoxicillin for 14 days, then amoxicillin for 14 more days; or 4) placebo (for steroid) + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days. Children were examined by otoscopy, tympanometry, and audiometry at entry and 2 and 4 weeks after entry; those without MEE at the 4-week visit returned monthly for up to 3 more visits or until recurrence of effusion. Serum immunoglobulin (Ig) G, IgM, IgA, and varicella titers were obtained at entry, and allergy skin testing was performed at the 4-week visit.

A total of 144 children was entered; 135 children (94%) returned for the 2-week visit, and 132 (92%) were seen for the 4-week visit. At the 2-week visit, 33.3% of children in the steroid + amoxicillin group had no MEE compared with 16.7% in the placebo + amoxicillin group (95% confidence interval for the difference in proportions: 2.4%-31.0%). At the 4-week visit, the percentage of children with no MEE in the steroid-treated group was 32.8%, whereas that in the placebo group was 20.0% (95% confidence interval for the difference in proportions in the 2 groups: -2.0%-27.7%). Comparing change in middle ear status from the 2- to the 4-week visit, there were no significant differences in recurrence of MEE or additional clearance of MEE between those who were treated with amoxicillin for 2 weeks and those who were treated for 4 weeks. By the 4-month visit, 68.4% of children who were in the steroid group and had no MEE at the 4-week visit had recurrence of MEE as did 69.2% of such children in the placebo group. A total of 126 (87.5%) children underwent allergy skin testing. Of the 122 children who had a positive reaction to histamine, 51 (41.8%) had 1 or more positive reactions to the test allergens. There was no difference in response to treatment between those with positive allergy tests and those without.

There was a significant difference in the proportion of children who were effusion-free immediately after 14 days of treatment with steroid and amoxicillin compared with those who were treated only with amoxicillin for 14 days. Within 2 weeks of finishing treatment, there was no longer any significant difference between the 2 groups regardless of whether amoxicillin was continued or not. Therefore, we conclude that treatment with the dose and type of steroid used in this study should not be universally recommended for treatment of chronic otitis media with effusion, and treatment with amoxicillin, if used, should not continue beyond 14 days.

The role of topical nasal steroids in the treatment of children with otitis media with effusion and/or adenoid hypertrophy.

Abstract:
Topical steroid treatment can be a powerful alternative to surgery in controlling adenoid hypertrophy and otitis media with effusion (OME).

A prospective, controlled, randomized, clinical study in an academic tertiary care center. A total of 122 children (3-15-year-old) on the waiting list for an adenoidectomy and/or ventilation tube placement were enrolled into the study and control groups. The study group (67 patients with adenoid hypertrophy, 34 of them with otitis media with effusion) received intranasal mometasone furoate monohydrate 100 mcg/day, and the control group (55 patients with adenoid hypertrophy, 29 of them with otitis media with effusion) was followed up without any treatment. All patients were evaluated at 0 and 6 weeks. The assessment of each patient included history, a symptom questionnaire, a skin prick test, a tympanogram, if possible a pure tone audiogram, and otoscopic and endoscopic examinations. The size of adenoid tissue was graded as a percentage according to obliteration of the choanae. The adenoid/choana ratio (A/C) was recorded for each patient. Symptoms were scored as 0 (absent), 1 (intermittent/periodic), or 2 (continuous). The data were analyzed with the "Statistical Package for the Social Sciences" (SPSS 9.0) using the appropriate nonparametric tests for nominal and ordinal data.

Resolution of otitis media with effusion in the study group (42.2%) was significantly higher than that in the control group (14.5%) (p<0.001). Forty-five patients (67.2%) with adenoid hypertrophy in the study group showed a significant decrease in adenoid size according to the endoscopic evaluation compared to the control group (p<0.001). A significant improvement in obstructive symptoms was seen in the study group (p<0.001). The endoscopically measured adenoid/choana ratio and degree of obstructive symptoms showed a significant correlation (r=0.838 p<0.001, r=0.879 p<0.001, r=0.838 p<0.001, r=0.879 p<0.001). The adenoid/choana ratio improved significantly in atopic patients in the study group (p<0.05), whereas in atopic patients in the control group there was no change (p=0.221).

Nasal mometasone furoate monohydrate treatment can significantly reduce adenoid hypertrophy and eliminate obstructive symptoms. It is a useful alternative to surgery, at least in the short term, for otitis media with effusion.

Management for the children with otitis media with effusion in the tertiary hospital.

Abstract:
Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.

Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.

Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).

In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.

A double-blind randomised placebo-controlled trial of topical intranasal corticosteroids in 4- to 11-year-old children with persistent bilateral otitis media with effusion in primary care.

Abstract:
To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion (OME).

A double-blind randomised placebo-controlled trial with an intention to treat analysis; the 10.6% of patients lost to follow-up at 1 month were censored in the analysis.

76 Medical Research Council General Practice Research Framework practices throughout the UK between 2004 and 2007.

A sample of 217 children aged 4-11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry (B B or B C2 types using a modified Jerger classification) at randomisation.

Mometasone 50 micrograms in each nostril or placebo spray once daily for 3 months.

The primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month. Secondary outcomes included clearance at 3 months and 9 months; adverse events; OM8-30 scores (a functional health status responsive disease-specific measure); hearing loss; days with otalgia; cost-effectiveness; and health utilities.

Of the topical steroid group, 40.6% (39/96) demonstrated tympanometric clearance (C1 or A type) in one or both ears at 1 month, compared with 44.9% (44/98) of the placebo group. The absolute risk reduction at 1 month was -4.3% (95% CI -18.05% to 9.26%); the odds ratio (OR) was 0.84 (95% CI 0.48 to 1.48). Four covariates were pre-specified for inclusion in logistic regression analysis: age as a continuous variable (p = 0.94), season (p = 0.70), atopy (p = 0.61) and clinical severity (p = 0.006). The adjusted OR (AOR) at 1 month for the main outcome was 0.93 (95% CI 0.50 to 1.75). Secondary analysis at 3 months showed 58.1% of the steroid group had resolved and 52.3% of the placebo group, AOR 1.45 (95% CI 0.74 to 2.84). At 9 months 55.6% of the treated group remained clear in at least one ear and 65.3% of the placebo group, AOR 0.82 (95% CI 0.39 to 1.75). Adverse events (although relatively minor) occurred in 7-22% of children and included nasal stinging, epistaxis, dry throat and cough. The OM8-30 scores (p = 0.55) reported hearing difficulty (p = 0.08), and days with otalgia (p = 0.46) were not significantly different between groups at 3 months. The economic evaluation found the active treatment arm to be dominated by placebo, accruing slightly (but not significantly) higher costs and fewer quality-adjusted life-years (QALYs), with a 24.2% probability that topical steroids are a cost-effective use of NHS resources at a ceiling ratio of 20,000 pounds per QALY gained.

Use of topical intranasal corticosteroids is very unlikely to be a clinically effective treatment for OME (glue ear) in the primary care setting.

Current Controlled Trials ISRCTN38988331.

Topical intranasal corticosteroids in 4-11 year old children with persistent bilateral otitis media with effusion in primary care: double blind randomised placebo controlled trial.

Abstract:
To determine the clinical effectiveness of topical intranasal corticosteroids in children with bilateral otitis media with effusion.

Double blind randomised placebo controlled trial.

76 Medical Research Council General Practice Research Framework practices throughout the United Kingdom, between 2004 and 2007.

217 children aged 4-11 years who had at least one practice recorded episode of otitis media or a related ear problem in the previous 12 months, and with bilateral otitis media with effusion confirmed by a research nurse using otoscopy plus micro-tympanometry (B/B or B/C2, modified Jerger types).

Mometasone furoate 50 microg or placebo spray given once daily into each nostril for three months.

Proportions of children cured of bilateral otitis media with effusion assessed with tympanometry (C1 or A type) at one month (primary end point), three months, and nine months; adverse events; three month diary symptoms. Results 41% (39/96) of the topical steroid group and 45% (44/98) of the placebo group were cured in one or both ears at one month (difference favouring placebo 4.3% (95% confidence interval -9.3% to 18.1%). Poisson regression was done with adjustment for four pre-specified covariates (clinical severity, P=0.003; atopy, P=0.67; age, P=0.92; season, P=0.71). The adjusted relative risk at one month was 0.97 (95% confidence interval 0.74 to 1.26). At three months, 58% of the topical steroid group and 52% of the placebo group were cured (relative risk 1.23, 0.84 to 1.80). Diary symptoms did not differ between the two groups, and no significant harms were reported.

Topical steroids are unlikely to be an effective treatment for otitis media with effusion in general practice. High rates of natural resolution occurred by 1-3 months.

Current Controlled Trials ISRCTN38988331; National Research Register NO575123823; MREC 03/11/073.

Hearing thresholds and tympanic membrane sequelae in children managed medically or surgically for otitis media with effusion.

Abstract:
To determine the long-term effects of ventilation tube insertion on hearing thresholds and tympanic membrane pathologic abnormalities in children with otitis media with effusion.

Prospective cohort study.

Tertiary care children's hospital, otorhinolaryngology and audiology service.

Patients aged 8 to 16 years who participated in a randomized controlled trial of medical vs surgical (ventilation tube [VT]) treatment for recurrent otitis media with effusion at ages 2.5 to 7 years.

Hearing thresholds and tympanic membrane sequelae.

One hundred thirteen of 125 children who had participated in the trial underwent blinded audiometric, tympanometric, otomicroscopic, and parental questionnaire evaluation 6 to 10 years following the trial. Thirty of 57 [corrected] medical subjects received ventilation tubes and 18 of 56 [corrected] VT subjects received more than 1 set of tubes. To evaluate sequelae risk associated with ventilation tubes independent of disease severity, we compared 27 medical subjects who never received ventilation tubes and 38 subjects randomized to VT who only received 1 set of tubes.

Tympanic membrane pathologic abnormalities were present in 81% of VT subjects and 19% of medical subjects (relative risk, 4.4; 95% confidence interval, 2.2-9.9). Hearing thresholds were 2.1 to 8.1 dB higher in subjects treated with tubes (P = .005).

In children who were candidates for ventilation tube insertion randomly assigned to receive medical or VT treatment for otitis media with effusion, elevated hearing thresholds and tympanic membrane pathologic abnormalities were more common in VT subjects 6 to 10 years after insertion.

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.

Abstract: This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.

Topical intranasal corticosteroids for otitis media with effusion in primary care.


Context: Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues.

To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment.

We included randomised controlled trials with individuals using drugs, alcohol, or both. Interventions were MI or motivational enhancement therapy (MET), delivered individually and face to face. Eligible control interventions were no intervention, treatment as usual, assessment and feedback, or other active intervention.

Maritally distressed women with alcohol problems: the impact of a short-term alcohol-focused intervention on drinking behaviour and marital satisfaction.

Abstract:
To evaluate the efficacy of a short-term alcohol-focused intervention for maritally distressed women, and to explore changes in relationship functioning.

Participants were assigned randomly to an alcohol-focused treatment or to a waiting-list control group. The waiting-list control group began the intervention at 1-month follow-up.

The intervention took place at a research and training centre offering outpatient psychology services to the community.

A sample of 32 women with alcohol and marital problems were recruited through the media. Participants reported protracted alcohol problems, moderate to severe impact of alcohol on social and occupational functioning, and moderate to severe marital distress.

Measures of average alcohol consumption, marital distress, relational efficacy and depression were administered at pre- and post-therapy, and at 1, 6 and 12-month follow-up.

The intervention involved six 1-hour sessions, consisting of clinical assessment, motivational interviewing, cognitive-behavioural strategies and relapse prevention.

At 1-month follow-up, the intervention was associated with statistically significant improvements in alcohol consumption, marital satisfaction, relational efficacy and depression, and these effects were sustained at 12-month follow-up.

At 1-month follow-up the intervention was associated with decreased alcohol consumption and depression, and increased marital satisfaction and relational efficacy, with evidence of maintained effects at 12-month follow-up. However, it is unlikely that reduced problem drinking and improved confidence in resolving problems were the only factors producing low marital quality in these couples. Further research is needed to identify those individuals who might benefit from marital interventions.

Clinical profile of participants in a brief intervention program for cannabis use disorder.

Abstract: The increasing demand for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and allocated to either a 6-session CBT program, a single-session brief intervention, or a delayed-treatment control group. This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program. While they report similar patterns of cannabis use to nontreatment samples, they report a range of serious health and psychosocial consequences. While they appear relatively socially stable, they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress, with the most commonly cited reason for cannabis use being stress relief. There were clinically relevant gender differences among the sample. This study provides more evidence of the demand for, and nature of issues relevant to, interventions for cannabis use disorders, and supports the need for further research into how best to assist individuals with these disorders.

A randomized controlled trial of motivational enhancement therapy (MET) for mild to moderate alcohol dependence.

Abstract:
This study was designed to conduct a randomized controlled trial of motivational enhancement therapy (MET) with two control conditions: nondirective reflective listening (NDRL) and no further counseling (NFC); and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence, in a "real-life" clinical setting.

Patients with mild to moderate alcohol dependence were recruited, assessed and treated at the Community Alcohol and Drug Service of Christchurch, New Zealand. All patients received a feedback/education session before randomization to either four sessions of MET, four sessions of NDRL, or NFC. Outcome data on 122 subjects (57.4% men) were obtained 6 months following the end of treatment, by an interviewer who was blind to the treatment condition. The primary drinking outcome was unequivocal heavy drinking, defined as drinking 10 or more standard drinks six or more times in the follow-up period. Global assessment scale (GAS) measured general personal/social functioning.

Of patients treated with MET, 42.9% showed unequivocal heavy drinking compared with 62.5% of the NDRL and 65.0% of the NFC groups (p = .04). No significant differences were found for GAS score according to treatment condition.

In patients with mild to moderate alcohol dependence, MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL. MET can be considered an effective "value added" counseling intervention in a real-life clinical setting. In patients with mild to moderate alcohol dependence, nondirective reflective listening provides no additional advantage over a feedback/education session alone.

Findings of a pilot study of motivational interviewing with pregnant drinkers.

Abstract:
Cost-effective interventions are needed for counseling pregnant drinkers, in order to reduce risk of fetal alcohol effects.

42 pregnant women who reported alcohol consumption participated in this pilot study of motivational interviewing. Following a comprehensive alcohol use assessment, the participants were randomly assigned to receive either written information about the risks related to drinking during pregnancy or a one-hour motivational interview. The motivational interview was an empathic, client-centered, but directive session focusing on the health of the participants' unborn babies.

At the end of a 2-month follow-up period, the 34 women (81%) who remained in the study showed a significant reduction in alcohol consumption and peak intoxication levels. Women who had reported the highest blood alcohol concentration (BAC) levels during early pregnancy showed a significantly greater reduction in their estimated BACs at follow-up (during later pregnancy) if assigned to the treatment rather than the control condition.

Motivational interviewing shows promise as a specific intervention for initiating a reduction in drinking among pregnant women who are at greatest risk. Simpler assessment and advice may suffice for women with lower initial consumption levels.

Motivational interviewing and treatment adherence among psychiatric and dually diagnosed patients.

Abstract: The effect of motivational interviewing on outpatient treatment adherence among psychiatric and dually diagnosed inpatients was investigated. Subjects were 121 psychiatric inpatients, 93 (77%) of whom had concomitant substance abuse/dependence disorders, who were randomly assigned to: a) standard treatment (ST), including pharmacotherapy, individual and group psychotherapy, activities therapy, milieu treatment, and discharge planning; or b) ST plus motivational interviewing (ST+MI), which involved 15 minutes of feedback on the results of a motivational assessment early in the hospitalization, and a 1-hour motivational interview just before discharge. Interviewers utilized motivational techniques described in Miller and Rollnick (1991), such as reflective listening, discussion of treatment obstacles, and elicitation of motivational statements. Results indicated that the proportion of patients who attended their first outpatient appointment was significantly higher for the ST+MI group (47%) than for the ST group (21%; chi2 = 8.87, df = 1, p<.01) overall, and for dually diagnosed patients (42% for ST+MI vs. 16% for ST only; chi2 = 7.68, df = 1, p<.01). Therefore, brief motivational interventions show promise in improving outpatient treatment adherence among psychiatric and dually diagnosed patients.

Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department.

Abstract: This study evaluated the use of a brief motivational interview (MI) to reduce alcohol-related consequences and use among adolescents treated in an emergency room (ER) following an alcohol-related event. Patients aged 18 to 19 years (N = 94) were randomly assigned to receive either MI or standard care (SC). Assessment and intervention were conducted in the ER during or after the patient's treatment. Follow-up assessments showed that patients who received the MI had a significantly lower incidence of drinking and driving, traffic violations, alcohol-related injuries, and alcohol-related problems than patients who received SC. Both conditions showed reduced alcohol consumption. The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking, beyond what was produced by the precipitating event plus SC alone.

Motivation to change substance use among offenders of domestic violence.

Abstract: Substance use alone leads to increased rates of violence, reduction in adherence to treatment regimes, and other negative psychiatric sequelae. Given the high rates of co-occurring substance use and family violence-related problems, substance use was assessed among offenders of domestic violence who were mandated by court to attend anger management classes. Rates of substance dependence diagnoses ranged from 33 to 50%, while rates of substance abuse diagnoses ranged from 60 to 75%. This study evaluated the effectiveness of a motivational enhancement intervention on readiness to change substance use. Two anger management groups were targeted to assess substance use, violence, and motivation to change substance use behaviors. One group was randomly chosen to partake in a motivational enhancement intervention session. The comparison group was offered standard anger management classes. Forty-one clients were evaluated for substance abuse and dependence diagnosis using criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. A brief motivation to change survey, adapted from the Readiness to Change subscale of the Stages of Change Readiness and Treatment Eagerness Scale was administered pre- and postsession. Results indicate that a motivational enhancement intervention is feasible and effective in increasing readiness to change substance use among domestic violence offenders. The results illustrate the importance of assessing and treating substance use among offenders of domestic violence, as this may be an important indicator for higher dropout rates and reoffenses among this population.

Motivational interviewing with psychiatrically ill substance abusing patients.

Abstract: This pilot study reports the relative efficacy of a one-session preadmission motivational interview (n = 13) compared to a standard preadmission interview (n = 10) for psychiatrically ill substance abusing patients in a partial hospital program.

Effects of a brief motivational intervention with college student drinkers.

Abstract: This study consisted of a randomized controlled trial of a 1-session motivational intervention for college student binge drinkers. Sixty students who reported binge drinking 2 or more times in the past 30 days were randomly assigned to either a no-treatment control or a brief intervention group. The intervention provided students with feedback regarding personal consumption, perceived drinking norms, alcohol-related problems, situations associated with heavy drinking, and alcohol expectancies. At 6-week follow-up, the brief intervention group exhibited significant reductions on number of drinks consumed per week, number of times drinking alcohol in the past month, and frequency of binge drinking in the past month. Estimates of typical student drinking mediated these reductions. This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change.

Comparison of extended versus brief treatments for marijuana use.

Abstract: Adult marijuana users (N = 291) seeking treatment were randomly assigned to an extended 14-session cognitive-behavioral group treatment (relapse prevention support group; RPSG), a brief 2-session individual treatment using motivational interviewing (individualized assessment and intervention; IAI), or a 4-month delayed treatment control (DTC) condition. Results indicated that marijuana use, dependence symptoms, and negative consequences were reduced significantly in relation to pretreatment levels at 1-, 4-, 7-, 13-, and 16-month follow-ups. Participants in the RPSG and IAI treatments showed significantly and substantially greater improvement than DTC participants at the 4-month follow-up. There were no significant differences between RPSG and IAI outcomes at any follow-up. The relative efficacy of brief versus extended interventions for chronic marijuana-using adults is discussed.


Context: Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved.

To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease.

We included randomised controlled trials (RCTs) of ERT in people with LOPD of any age.

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.

Abstract:
Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease.

We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period.

Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI -0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]).

We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease.

Sanofi Genzyme.

Correction to Lancet Neurol 2021; 20: 1012-16.

Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease.

Abstract: This 52-week, phase I/II double-blind, randomized, placebo-controlled study investigated the novel use of clenbuterol in late-onset Pompe disease (LOPD) stably treated with ERT. Eleven of thirteen participants completed the study. No serious adverse events were related to clenbuterol, and transient minor adverse events included mild elevations of creatine kinase, muscle spasms, and tremors. At week 52, the 6-min walk test distance increased by a mean of 16 m (p = 0.08), or a mean of 3% of predicted performance (p = 0.03), and the maximum inspiratory pressure increased 8% (p = 0.003) for the clenbuterol group. The quick motor function test score improved by a mean of seven points (p = 0.007); and the gait, stairs, gower, chair test improved by a mean of two points (p = 0.004). Clenbuterol decreased glycogen content in the vastus lateralis by 50% at week 52. Transcriptome analysis revealed more normal muscle gene expression for 38 of 44 genes related to Pompe disease following clenbuterol. The placebo group demonstrated no significant changes over the course of the study. This study provides initial evidence for safety and efficacy of adjunctive clenbuterol in patients with LOPD (NCT01942590).

Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.

Abstract: This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. Twelve of 13 participants completed the study. No serious adverse events were related to albuterol, and transient minor drug-related adverse events included muscle spasms and tremors. For the albuterol group, forced vital capacity in the supine position increased by 10% (p < .005), and forced expiratory volume in one second increased by 8% (p < .05); the six-minute walk test increased 25 m (p < .05; excluding one participant unable to complete muscle function testing); the Gross Motor Function Measure increased by 8% (p < .005) with the greatest increases in the Standing (18%; p < .05) and Walking, Running, and Jumping (11%; p < .005) subtests. No significant improvements would be expected in patients with late-onset Pompe disease who were stably treated with enzyme replacement therapy. The placebo group demonstrated no significant increases in performance on any measure. These data support a potential benefit of extended-release albuterol as adjunctive therapy in carefully selected patients with late-onset Pompe disease based on ability to take albuterol on enzyme replacement therapy (NCT01885936).

Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial.

Abstract:
Pompe disease is a rare disorder characterised by progressive loss of muscle and respiratory function due to acid α-glucosidase deficiency. Enzyme replacement therapy with recombinant human acid α-glucosidase, alglucosidase alfa, is the first approved treatment for the disease, but some patients do not respond, and many do not show a sustained benefit. We aimed to assess the safety and efficacy of an investigational two-component therapy (cipaglucosidase alfa, a novel recombinant human acid α-glucosidase, plus miglustat, an enzyme stabiliser) for late-onset Pompe disease.

We did a randomised, double-blind, parallel-group, phase 3 trial at 62 neuromuscular and metabolic medical centres in 24 countries in the Americas, Asia-Pacific, and Europe. Eligible participants were aged 18 years or older with late-onset Pompe disease, and had either been receiving alglucosidase alfa for at least 2 years or were enzyme replacement therapy-naive. Participants were randomly assigned (2:1) using interactive response technology software, stratified by 6-min walk distance and previous enzyme replacement therapy status, to intravenous cipaglucosidase alfa (20 mg/kg) plus oral miglustat or to intravenous alglucosidase alfa (20 mg/kg) plus oral placebo once every 2 weeks for 52 weeks. Patients, investigators, and outcome assessors were masked to treatment assignment. The primary endpoint was change from baseline to week 52 in 6-min walk distance, assessed using a mixed-effect model for repeated measures analysis for comparison of superiority in the intention-to-treat population (all patients who received at least one dose of study drug). This study is now complete and is registered with ClinicalTrials.gov, NCT03729362.

Between Dec 3, 2018, and Nov 26, 2019, 130 patients were screened for eligibility and 125 were enrolled and randomly assigned to receive cipaglucosidase alfa plus miglustat (n=85) or alglucosidase alfa plus placebo (n=40). Two patients in the alglucosidase alfa plus placebo group did not receive any dose due to absence of genotype confirmation of late-onset Pompe disease and were excluded from analysis. Six patients discontinued (one in the alglucosidase alfa plus placebo group, five in the cipaglucosidase alfa plus miglustat group), and 117 completed the study. At week 52, mean change from baseline in 6-min walk distance was 20·8 m (SE 4·6) in the cipaglucosidase alfa plus miglustat group versus 7·2 m (6·6) in the alglucosidase alfa plus placebo group using last observation carried forward (between-group difference 13·6 m [95% CI -2·8 to 29·9]). 118 (96%) of 123 patients experienced at least one treatment-emergent adverse event during the study; the incidence was similar between the cipaglucosidase alfa plus miglustat group (n=81 [95%]) and the alglucosidase alfa plus placebo group (n=37 [97%]). The most frequently reported treatment-emergent adverse events were fall (25 [29%] patients in the cipaglucosidase alfa plus miglustat group vs 15 [39%] in the alglucosidase alfa plus placebo group), headache (20 [24%] vs 9 [24%]), nasopharyngitis (19 [22%] vs 3 [8%]), myalgia (14 [16%] vs 5 [13%]), and arthralgia (13 [15%]) vs 5 [13%]). 12 serious adverse events occurred in eight patients in the cipaglucosidase alfa plus miglustat group; only one event (anaphylaxis) was deemed related to study drug. One serious adverse event (stroke) occurred in the alglucosidase alfa plus placebo group, which was deemed unrelated to study drug. There were no deaths.

Cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in our overall population of patients with late-onset Pompe disease. Further studies should investigate the longer-term safety and efficacy of cipaglucosidase alfa plus miglustat and whether this investigational two-component therapy might provide benefits, particularly in respiratory function and in patients who have been receiving enzyme replacement therapy for more than 2 years, as suggested by our secondary and subgroup analyses.

Amicus Therapeutics.

Cardiovascular abnormalities in late-onset Pompe disease and response to enzyme replacement therapy.

Abstract:
We evaluated the prevalence of cardiovascular abnormalities and the efficacy and safety of enzyme replacement therapy in patients with late-onset Pompe disease.

Ninety patients were randomized 2:1 to enzyme replacement therapy or placebo in a double-blinded protocol. Electrocardiograms and echocardiograms were obtained at baseline and scheduled intervals during the 78-week study period. Baseline cardiovascular abnormalities, and efficacy and safety of enzyme replacement therapy were described. Three pediatric patients were excluded.

Eighty-seven patients were included. Median age was 44 years; 51% were men. At baseline, a short PR interval was present in 10%, 7% had decreased left ventricular systolic function, and 5% had elevated left ventricular mass on echocardiogram (all in mild range). There was no change in cardiovascular status associated with enzyme replacement therapy. No significant safety concerns related to enzyme replacement therapy were identified.

Although some patients with late-onset Pompe disease had abnormalities on baseline electrocardiogram or echocardiogram, those classically seen in infantile Pompe disease, such as significant ventricular hypertrophy, were not noted. Cardiovascular parameters were not impacted by enzyme replacement therapy, and there were no cardiovascular safety concerns. The cardiovascular abnormalities identified may be related to Pompe disease or other comorbid conditions.

A randomized study of alglucosidase alfa in late-onset Pompe's disease.

Abstract:
Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.

Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).

At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).

In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)


Context: Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain.

To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled').

We included randomised controlled trials (RCTs) in children under 18 years of age undergoing surgery that compared diclofenac (delivered in any dose and route) to placebo or any active pharmacological intervention. We included RCTs comparing different administration routes of diclofenac and different strategies.

Effect of pre-operative rectal diclofenac suppository on post-operative analgesic requirement in cleft palate repair: A randomised clinical trial.

Abstract:
Opioid analgesics used for analgesia are associated with sedation, respiratory depression and post-operative nausea and vomiting. Non-steroidal anti-inflammatory drugs such as diclofenac are a safe and effective alternative with opioid-sparing effect.

To evaluate the effectiveness of pre-operative rectal diclofenac suppository (1 mg/kg) in cleft palate repair for post-operative analgesia and reduction in post-operative opioid requirements.

A randomized clinical trial.

After obtaining approval from the institutional ethical committee, 60 children were allocated by a computer-generated randomisation into two groups of 30 each; group D (Diclofenac group) and group C (Conventional group). Children in group D and group C were similar in all aspects except for the fact that group D children received 1 mg/kg diclofenac suppository after induction. Pain was evaluated using modification of the objective pain scale by Hannallah and colleagues for 6 h post-operatively by an anaesthesiology resident or nursing staff who was blinded to the group. If the pain score was more than 3, rescue analgesic I.V. fentanyl 0.5 μgm/kg was administered. The pain scores at different intervals, number of doses and quantity of rescue analgesic required were noted.

We observed that pre-operative rectal diclofenac provided effective analgesia in the immediate post-operative period, as evidenced by reduced pain scores and reduced opioid requirement (P=0.00002). There was no evidence of any increased perioperative bleeding in the diclofenac group.

Pre-operative rectal diclofenac reduces opioid consumption and provides good post-operative analgesia.

Comparison Between Efficacy of Transdermal Ketoprofen and Diclofenac Patch in Patients Undergoing Therapeutic Extraction-A Randomized Prospective Split Mouth Study.

Abstract:
Postoperative pain control is a significant aspect of patient treatment after an oral and maxillofacial surgical procedure. The use of a transdermal patch is one such method to provide postoperative analgesia. The present study was undertaken to investigate the efficacy of a single-dose transdermal patch of ketoprofen compared with that of diclofenac postoperatively after therapeutic extraction of first premolar teeth for patients undergoing orthodontic treatment.

A split mouth randomized clinical trial was conducted of 40 patients aged 15 to 25 years who had required therapeutic extraction of both maxillary and mandibular first premolar teeth bilaterally. A single ketoprofen patch was applied for the first and fourth quadrant extraction, and diclofenac patch was applied for the second and third quadrant extraction after atraumatic therapeutic exodontia at 2 consecutive appointments with the patient under local anesthesia. The data were obtained and analyzed using the Student t test and Shapiro-Wilk test using SPSS software (IBM Corp, Armonk, NY).

All 40 patients who had received a single-dose ketoprofen patch had experienced less postoperative pain and did not require a rescue analgesic with a mean visual analog scale (VAS) score of 1.13 ± 0.335 (P < .00001). The patients who had received a diclofenac patch reported comparatively elevated pain scores in the initial 24 hours, with a mean VAS score of 2.0 ± 0.5064 postoperatively, and 20% of the diclofenac treatment arm had required a rescue analgesic. No complications were observed among the patients postoperatively in either treatment arm.

Both the ketoprofen and diclofenac transdermal patches were effective in achieving postoperative analgesia in patients after therapeutic extraction, with ketoprofen superior to diclofenac as a transdermal medicament.

Tramadol vs. diclofenac for posttonsillectomy analgesia.

Abstract:
To compare the analgesic efficacy of oral tramadol hydrochloride and oral diclofenac sodium for posttonsillectomy pain management.

Single-blind (surgeon and research team members), prospective, randomized, controlled clinical trial.

Sixty-four patients 11 years and older undergoing bipolar electrocautery tonsillectomy were randomized to either the oral tramadol or the oral diclofenac postoperative pain group. Patients recorded pain levels twice daily for 14 days using a visual analogue scale.

Pain scores for the 14 days were not significantly different between the oral tramadol and oral diclofenac groups. There were no significant differences in the incidence of postoperative hemorrhage and hospital readmission for uncontrolled pain.

Oral tramadol can deliver the same analgesic efficacy as oral diclofenac for posttonsillectomy pain relief, which might be beneficial for avoiding the adverse effects of nonsteroidal anti-inflammatory drug therapy.

Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA.

Abstract:
Because of its pain-attenuating and sedative properties oral ketamine has been used as premedication in children and adults. We wanted to compare in children scheduled for adenoidectomy safety and efficacy of oral ketamine with a premedication that causes similar preoperative sedation and relief of pain at the venepuncture site. We also evaluated the effect of i.v. glycopyrrolate added to these combinations.

One hundred children between 10 and 15 kg of body weight scheduled for day-case adenoidectomy were randomly assigned to one of four groups: groups DG and DS received diclofenac 12.5 mg and diazepam 0.5 mg/kg rectally, EMLA cream at the venepuncture site, and placebo orally; groups KG and KS received ketamine 6.0 mg/kg orally, placebo cream at the puncture site, and placebo rectally; additionally, groups DG and KG received glycopyrrolate 5 microg/kg, and groups DS and KS received placebo intravenously. We recorded perioperatively scores (open scale 1-9) for stridor, sedation, bleeding, nausea, pain, heart rate, the need for analgesics and registered psychotomimesis and well-being at home.

The children of the K-groups became more tearful during separation from their parents (P=0.0072). No other differences were found between the ketamine and diazepam/diclofenac groups before and after premedication until induction of anaesthesia. Oral ketamine produced unpleasant psychotomimesis in four out of 59 children. During the first 10 min postoperatively, the score for stridor was significantly higher in group KS than in the D-groups; stridor scores > or = 6 were seen in one child of the D-groups (DS) and in six children of the K-groups (n.s.), of whom three developed laryngospasm (one reintubation). Glycopyrrolate diminished salivation in all groups, but had no effect on stridor scores. Additionally, glycopyrrolate delayed the onset of eating at home.

Premedication with racemic oral ketamine 6 mg/kg does not seem to be suitable for upper airway procedures. Addition of i.v. glycopyrrolate before the induction of anaesthesia significantly reduced the scores for salivation.

The effect of a combination of rectal diclofenac and caudal bupivacaine on postoperative analgesia in children.

Abstract: Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used in the management of postoperative pain in children. The aim of the present study was to evaluate the combination of caudal analgesia and rectally administered diclofenac in the treatment of pain following minor surgery in children. Thirty-nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were randomly assigned to receive either a caudal block using 0.125% bupivacaine with adrenaline or a similar caudal block in combination with rectally administered diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to need analgesia in the first 24 h postoperatively. It would appear that the combination of a caudal block and rectal diclofenac in children undergoing minor lower abdominal surgery reduces the need for subsequent analgesia.

Postoperative analgesia using diclofenac and acetaminophen in children.

Abstract:
Diclofenac dosing in children for analgesia is currently extrapolated from adult data. Oral diclofenac 1.0 mg·kg(-1) is recommended for children aged 1-12 years. Analgesic effect from combination diclofenac/acetaminophen is unknown.

Children (n = 151) undergoing tonsillectomy (c. 1995) were randomized to receive acetaminophen elixir 40 mg·kg(-1) before surgery and 20 mg·kg(-1) rectally at the end of surgery with diclofenac suspension 0.1 mg·kg(-1) , 0.5 mg·kg(-1) , or 2.0 mg·kg(-1) before surgery or placebo. A further 93 children were randomized to receive diclofenac 0.1 mg·kg(-1) , 0.5 mg·kg(-1) , or 2.0 mg·kg(-1) only. Postoperative pain was assessed (visual analogue score, VAS 0-10) at half-hourly intervals from waking until discharge. Data were pooled with those from a further 222 children and 30 adults. One-compartment models with first-order absorption and elimination described the pharmacokinetics of both medicines. Combined drug effects were described using a modified EMAX model with an interaction term. An interval-censored model described the hazard of study dropout.

Analgesia onset had an equilibration half-time of 0.496 h for acetaminophen and 0.23 h for diclofenac. The maximum effect (EMAX ) was 4.9. The concentration resulting in 50% of EMAX (C50 ) was 1.23 mg·l(-1) for diclofenac and 13.3 mg·l(-1) for acetaminophen. A peak placebo effect of 6.8 occurred at 4 h. Drug effects were additive. The hazard of dropping out was related to pain (hazard ratio of 1.35 per unit change in pain). Diclofenac 1.0 mg·kg(-1) with acetaminophen 15 mg·kg(-1) achieves equivalent analgesia to acetaminophen 30 mg·kg(-1) .

Combination therapy can be used to achieve similar analgesia with lower doses of both drugs.

Oral dexamethasone decreases postoperative pain, swelling, and trismus more than diclofenac following third molar removal: a randomized controlled clinical trial.

Abstract:
The aim of this study was to compare the anti-inflammatory potential of two pharmacotherapy protocols based on the parameters of pain, trismus, and swelling, after extraction of third molars.

Thirty patients selected with symmetrical impaction of third molars were submitted to surgical procedures in both sides in different times. For one group, dexamethasone was used for 3 days, and for another group diclofenac sodium was also used for the same period. The main variables analyzed were the visual analogue pain scale (VAS), but others were also analyzed such as swelling and trismus, which were submitted to statistical analysis.

The results had no difference regarding the length of procedures (p = 0.986) and the pain in the immediate and 4-h postoperative period (p = 0.723 and 0.541). The rescue analgesic consumption was higher (p < 0.05) when using the protocol with diclofenac sodium. The variables mouth opening (p < 0.05) and swelling (p < 0.05) were significantly better when using the protocol with dexamethasone in the postoperative period.

Medical protocol with the use of dexamethasone in the postoperative period was more effective in controlling pain, trismus, and swelling, after the extraction of third molars, when compared to diclofenac sodium.

A randomised controlled trial of two analgesic techniques for paediatric tonsillectomy*.

Abstract: Investigators from Bristol described a fentanyl- and diclofenac-based analgesic technique for tonsillectomy with low postoperative nausea and vomiting rates and low pain scores. This study compared the effectiveness of a modified Bristol technique with a codeine-based regimen with respect to PONV and analgesia. Sixty-five children, ASA 1-2, were randomly assigned to either the Bristol group (fentanyl 1-2 μg.kg(-1) and diclofenac 1-2 mg.kg(-1)) or codeine group (codeine 1.5 mg.kg(-1)). All children received paracetamol 15 mg.kg(-1) and dexamethasone 0.1 mg.kg(-1) . Postoperative nausea and vomiting and pain scores were recorded hourly, and fitness for discharge was assessed at 4 h. The overall incidence of postoperative nausea and vomiting was 21% with no difference between groups (Bristol group 8/30, codeine group 5/32, p = 0.29). Children in the Bristol group required analgesia earlier than those in the codeine group (p < 0.005), but maximum pain scores were not different (Bristol group median (IQR [range) 4.5 (3-5 [0-5]), codeine group 4.0 (2-5 [1-5]), p = 0.15). Twenty-three per cent of children were assessed as not fit for discharge at 4 h. The codeine-based regimen may have a small advantage over the Bristol regimen, but neither technique seems ideally suited for a day-case service without a longer period of observation. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Comparison of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia.

Abstract:
Traditionally, pain in children is a topic that has received only minimal attention. However, in the recent times, considerable progress has been made in the field of neonatal and pediatric pharmacology. The concept of preemptive analgesia is important in combating postoperative pain in children. In this study, we sought to compare the effectiveness of preemptive analgesia provided by paracetamol alone and by its combination with diclofenac when administered per rectum.

To compare the efficacy of preoperative rectal paracetamol with paracetamol - diclofenac combination for postoperative analgesia in pediatric surgeries under general anesthesia.

Prospective randomized double-blind study.

Sixty children scheduled for various surgeries under general anesthesia were randomly allocated into two Groups A and B, with 30 in each. Children in Group A received paracetamol suppository 20 mg/kg and those in Group B received paracetamol 20 mg/kg + diclofenac 2 mg/kg as suppository immediately after tracheal intubation. All the children were assessed for 24 h from the time of extubation. The pain was measured using numerical rating scale in children above 7 years and face-legs-activity-cry-consolability scale in children below 7 years. The time interval between extubation and the administration of the first dose of rescue analgesic was taken as the duration of postoperative analgesia.

Descriptive and inferential statistical methods were used to analyze the data.

The duration of postoperative analgesia was significantly longer in paracetamol + diclofenac group (21.13 ± 2.68 h) as compared to paracetamol alone group (10.18 ± 2.39 h).

The combination of paracetamol and diclofenac administered per rectum preoperatively is more effective than paracetamol alone in providing postoperative analgesia in children.