Drug interventions for the treatment of obesity in children and adolescents

BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information. MAIN RESULTS: We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m(2) (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children. AUTHORS' CONCLUSIONS: This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials

Non-hip fracture-associated trauma in the elderly population

BACKGROUNDThe rate of trauma in the elderly is growing.OBJECTIVESTo evaluate the characteristics of non-hip fracture-associated trauma in elderly patients at a level I trauma center.METHODSThe study database of this retrospective cohort study was the trauma registry of a level I trauma center. Trauma patients admitted from January 2001 to December 2003 were stratified into different age groups. Patients with the diagnosis of hip fracture were excluded.RESULTSThe study group comprised 7629 patients. The non-hip fracture elderly group consisted of 1067 patients, 63.3% women and 36.7% men. The predominant mechanism of injury was falls (70.5%) and most of the injuries were blunt (94.1%). Injury Severity Score was found to increase significantly with age. The average mortality rate among the elderly was 6.1%. Age, ISS, Glasgow Coma Score on admission, and systolic blood pressure on admission were found to be independent predictors of mortality.CONCLUSIONSFalls remain the predominant cause of injury in the elderly. Since risk factors for mortality can be identified, an effective community prevention program can help combat the future expected increase in morbidity and mortality associated with trauma in the elderly

ALCOHOL USE AMONG TRAUMA VICTIMS ADMITTED TO A LEVEL I TRAUMA CENTER IN ISRAEL.

מטרה: לקבוע את שיעור מקרי הטראומה שנגרמו כתוצאה משימוש באלכוהול ולבחון את מאפייניהם. שיטה: ניתוח נתונים על 854 מטופלים מתוך 5,529 מטופלים שהופיעו ברישום הטראומה הישראלי בשנים 2001-.2003 מן הממצאים: אצל 170 מהפונים נמצאה רמה גבוהה של אלכוהול בדם. בקרב אלה היה שיעור תאונות הדרכים גבוה מזה שבקרב הנפגעים ללא האלכוהול (35% לעומת 24%) וכך גם לגבי דקירות (29% לעומת 7%). חומרת הפגיעות בקרב קבוצת ה"אלכוהול" הייתה רבה יותר ושיעורי הלא-יהודים, הצעירים, והגברים בקבוצה זו היו גבוהים מהשיעורים אצל שאר הנבדקים. רוב הפגיעות המיוחסות לאלכוהול התרחשו בסופי שבוע ובשעות הערב-לילה

Ultrasonography for the evaluation of abdominal trauma in multiple casualty incidents

Objective: Ultrasound (US) is commonly used for the diagnosis of hemoperitoneum in trauma patients. The use of US in the evaluation of abdominal injury during multiple casualty incidents (MCIs) has been described, but never evaluated. The purpose of this study was to determine the accuracy of US for evaluation of the unique injury patterns associated with MICs. Patients and methods: We conducted a retrospective study of patients admitted to a Level 1 trauma center during MCIs resulting from terrorist attacks in the Tel-Aviv area. Results: During the 4-year study period there were 43 patients who had an US examination as part of their initial assessment. The overall accuracy of the US examination was 77%, with a sensitivity of 40%, and a specificity of 88%. The positive predictive value (PPV) was 50%, and the negative predictive value (NPV) was 83%. Conclusions: Although US examination lacks the sensitivity to be used alone in determining operative intervention in the evaluation of patients admitted in an MCI, a reasonable specificity might justify its use as a screening tool in MCIs