Mouaz Alsawas

Treatment of pediatric obesity: An umbrella systematic review

Objective Multiple interventions are available to reduce excess body weight in children. We appraised the quality of evidence supporting each intervention and assessed the effectiveness on different obesity-related outcomes. Methods We conducted a systematic search for systematic reviews of randomized controlled trials evaluating pediatric obesity interventions applied for ≥6 months. We assessed the quality of evidence for each intervention using GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. Results From 16 systematic reviews, we identified 133 eligible randomized controlled trials. Physical activity interventions reduced systolic blood pressure and fasting glucose (low to moderate quality of evidence). Dietary interventions with low-carbohydrate diets had a similar effect to low-fat diets in terms of body mass index (BMI) reduction (moderate quality of evidence). Educational interventions reduced waist circumference, BMI, and diastolic blood pressure (low quality of evidence). Pharmacological interventions reduced BMI (metformin, sibutramine, orlistat) and waist circumference (sibutramine, orlistat) and increased high-density lipoprotein cholesterol (sibutramine) but also raised systolic and diastolic blood pressure (sibutramine). Surgical interventions (laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) resulted in the largest BMI reduction (moderate quality of evidence). Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education significantly reduced systolic and diastolic blood pressure, BMI, and triglycerides. Combined parent-child interventions and parent-only interventions had similar effects on BMI (low quality of evidence). Conclusions Several childhood obesity interventions are effective in improving metabolic and anthropometric measures. A comprehensive multicomponent intervention, however, appears to have the best overall outcomes.

Clinical features and management of non-HIV related lipodystrophy in children: a systematic review

Context: Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. Objective: We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, < 18 years). Data Source: Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016. Study Selection: Search terms included lipodystrophy, and age 0 to 18 years. Patients with unambiguous diagnosis of lipodystrophy were included. Lipodystrophy secondary to HIV treatment was excluded. Data Synthesis: We identified 1141 patients from 351 studies. Generalized fat loss involving face, neck, abdomen, thorax, and upper and lower limbs was explicitly reported in 65% to 93% of patients with congenital generalized lipodystrophy (CGL) and acquired generalized lipodystrophy (AGL). In familial partial lipodystrophy (FPL), fat loss occurred from upper and lower limbs, with sparing of face and neck. In acquired partial lipodystrophy (APL), upper limbs were involved while lower limbs were spared. Other features were prominent musculature, acromegaloid, acanthosis nigricans and hepatosplenomegaly. Diabetes mellitus was diagnosed in 48% (n = 222) of patients with CGL (mean age at onset, 5.3 years). Hypertriglyceridemia was observed in CGL, AGL and FPL. Multiple interventions were used, with most patients receiving ≥ 3 interventions and being ≥ 18 years of age at the initiation of interventions. Conclusions: To our knowledge, this is the largest reported pooled database describing lipodystrophy patients with age at onset < 18 years. We have suggested core and supportive clinical features and summarized data on available interventions, outcomes and mortality.

The Association Between Celiac Disease and Eosinophilic Esophagitis: Mayo Experience and Meta-analysis of the Literature

Background: The association between celiac disease (CD) and eosinophilic esophagitis (EoE) has been the focus of multiple studies with variable results. Both diseases are immune mediated, and dietary triggers play a role in their pathogenesis. Objectives: The aim of the study was to analyze the risk of EoE in children with CD, assess the magnitude of association between CD and EoE in children, and report the characteristics and outcomes of children with both conditions. Methods: We conducted a retrospective study of the Mayo Clinic Electronic medical records between January 1, 1998 and December 31, 2015. Systematic review and meta-analysis of multiple databases was conducted to include studies reporting on the same association. Random-effects model was used to report pooled odds ratio (OR) and 95% confidence interval (CI). Results: In this cohort study, of 10,201 children who underwent at least 1 endoscopy, 595 had EoE, and 546 had CD. The risk of having EoE was not increased in children with CD compared to those without CD (OR, 0.29; 95% CI, 0.154–0.545). Nine of 10 children improved with gluten-free diet, topical glucocorticosteroid, and/or elimination diet. One child lost to follow-up. Meta-analysis of 5 studies showed similar results (OR, 0.525; 95% CI, 0.364–0.797). A total of 45 cases in the literature had both CD and EoE (mean age, 10 years; 64% boys; majority presenting with abdominal pain, vomiting, and diarrhea). Conclusions: Based on our cohort and the observational data, the diagnosis of CD in children is not associated with increased risk of EoE.

The Association of Weight Loss and Cardiometabolic Outcomes in Obese Children: Systematic Review and Meta-regression

Background Excess body weight in children is associated with multiple immediate and long-term medical comorbidities. We aimed to identify the degree of reduction in excess body weight associated with cardiometabolic changes (lipid panel, liver function tests, systolic blood pressure (SBP), diastolic blood pressure, glycosylated hemoglobin, and fasting blood glucose) in overweight and obese children. Methods We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through February 12, 2015. We included randomized controlled trials and cohort studies that evaluated interventions to treat pediatric obesity (medication, surgery, lifestyle, and community-based interventions) with ≥ a 6-month follow-up. We used a random effects meta-regression approach to assess the association between body mass index (BMI)/weight and cardiometabolic changes. Results We included 42 studies (37 randomized controlled trials and five cohorts) enrolling 3807 children (mean age, 12.2 years; weight, 74.7 kg; and BMI, 31.7 kg/m2). Studies had overall moderate to low risk of bias. A 1-mm Hg decrease in SBP was significantly associated with a decrease of 0.16 kg/m2 (P = .04) in BMI. A 1-mg/dL increase in HDL was significantly associated with a 0.74-kg decrease in weight (P = .02). A 1-mg/dL decrease in triglycerides was significantly associated with a 0.1-kg decrease in weight (P = .03). The remaining associations were not statistically significant. Conclusions Weight reduction in children is associated with significant changes in several cardiometabolic outcomes, particularly HDL, SBP, and triglycerides. The magnitude of improvement may help in setting expectations and may inform shared decision-making and counseling.

Non-pharmacological treatment of depression: a systematic review and evidence map

Background The comparative effectiveness of non-pharmacological treatments of depression remains unclear. Methods We conducted an overview of systematic reviews to identify randomised controlled trials (RCTs) that compared the efficacy and adverse effects of non-pharmacological treatments of depression. We searched multiple electronic databases through February 2016 without language restrictions. Pairs of reviewers determined eligibility, extracted data and assessed risk of bias. Meta-analyses were conducted when appropriate. Result We included 367 RCTs enrolling ∼20 000 patients treated with 11 treatments leading to 17 unique head-to-head comparisons. Cognitive behavioural therapy, naturopathic therapy, biological interventions and physical activity interventions reduced depression severity as measured using standardised scales. However, the relative efficacy among these non-pharmacological interventions was lacking. The effect of these interventions on clinical response and remission was unclear. Adverse events were lower than antidepressants. Limitation The quality of evidence was low to moderate due to inconsistency and unclear or high risk of bias, limiting our confidence in findings. Conclusions Non-pharmacological therapies of depression reduce depression symptoms and should be considered along with antidepressant therapy for the treatment of mild-to-severe depression. A shared decision-making approach is needed to choose between non-pharmacological therapies based on values, preferences, clinical and social context.

Comparative Effectiveness and Safety of Cognitive Behavioral Therapy and Pharmacotherapy for Childhood Anxiety Disorders: A Systematic Review and Meta-analysis

Importance Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. Objectives To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. Data Sources We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. Study Selection Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. Data Extraction and Synthesis Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. Main Outcomes and Measures Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. Results A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. Conclusions and Relevance Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

Grading the quality of evidence in complex interventions: a guide for evidence-based practitioners

Evidence-based practitioners who want to apply evidence from complex interventions to the care of their patients are often challenged by the difficulty of grading the quality of this evidence. Using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and an illustrative example, we propose a framework for evaluating the quality of evidence that depends on obtaining feedback from the evidence user (eg, guideline panel) to inform: (1) proper framing of the question, (2) judgements about directness and consistency of evidence and (3) the need for additional contextual and qualitative evidence. Using this framework, different evidence users and based on their needs would consider the same evidence as high, moderate, low or very low.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study

Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta‐analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5‐48] RCTs per MA) with average follow‐up of 24 (range, 1‐168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12‐3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow‐up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow‐up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

Tuberculin Skin Test Conversions and Occupational Exposure Risk in US Healthcare Workers

Background Healthcare workers (HCWs) undergo occupational tuberculosis screening at regular intervals. However, the risk of contracting tuberculosis at the workplace in a setting with a low background tuberculosis incidence is unclear. We aimed to evaluate the risk of tuberculin skin test (TST) conversion and the risk of occupational tuberculosis infection among HCWs in such a setting. Methods We conducted a retrospective cohort study of employees of a large tertiary medical center in the US Midwest who had undergone TST screening during the study period 1 January 1998 to 31 May 2014. Results Among 40142 HCWs who received a TST, only 123 converted over 16.4 years. Only 9 (7%) of the converters had a suspected tuberculosis exposure at the workplace and none developed active tuberculosis. The majority of TST converters (66%) had a negative QuantiFERON-TB test at the time of the conversion. Conclusions In one of the largest cohorts of HCWs in a low-tuberculosis-incidence setting, we demonstrated an extremely low risk of occupational tuberculosis exposure among TST converters and no resulting active tuberculosis cases. In this setting, the approach of testing HCWs at baseline and after tuberculosis exposure, rather than at regular intervals, should be considered.

Impact of Multiple Chronic Conditions in Patients Hospitalized with Stroke and Transient Ischemic Attack

BACKGROUND The prevalence and clinical impact of chronic conditions (CCs) have increasingly been recognized as an important public health concern. We evaluated the prevalence of coexisting CCs and their association with 30-day mortality and readmission in hospitalized patients with stroke and transient ischemic attack (TIA). METHODS In a retrospective study of patients aged ≥18 years hospitalized for first-ever stroke and TIA, we assessed the prevalence of coexisting CCs and their predictive value for subsequent 30-day mortality and readmission. RESULTS Study cohort comprised 6771 patients, hospitalized for stroke (n = 4068) and TIA (n = 2703), 51.4% men, with mean age of 68.2 years (standard deviation: ±15.6), mean number of CCs of 2.9 (±1.7), 30-day mortality rate of 8.6% (entire cohort), and 30-day readmission rate of 9.7% (in 2498 patients limited to Olmsted and surrounding counties). In multivariable models, significant predictors of (1) 30-day mortality were coexisting heart failure (HF) (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.09-1.92), cardiac arrhythmia (OR: 1.74, 95% CI: 1.40-2.17), coronary artery disease (CAD) (OR: 1.64, 95% CI: 1.29-2.08), cancer (OR: 1.67, 95% CI: 1.31-2.14), and diabetes (HR: 1.28, 95% CI: 1.01-1.62); and (2) 30-day readmission (n = 2498) were CAD (OR: 1.50, 95% CI: 1.09-2.07), cancer (OR: 1.46, 95% CI: 1.01-2.10), and arthritis (OR: 1.62, 95% CI: 1.09-2.40). CONCLUSIONS In patients hospitalized with stroke and TIA, CCs are highly prevalent and influence 30-day mortality and readmission. Optimal therapeutic and lifestyle interventions for CAD, HF, cardiac arrhythmia, cancer, diabetes, and arthritis may improve early clinical outcome.