Citations

Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence‐based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate‐quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate‐quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low‐quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen‐positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen‐negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low‐level viremia. Conclusion: Most of the current literature focuses on the immune active phases of chronic HBV infection; decision‐making in other commonly encountered and challenging clinical settings depends on indirect evidence. (H epatology 2016;63:284–306)

Objectives: The objective was to assess the effect of menopausal hormonal therapy (MHT) on all-cause and cause-specific mortality. Methods: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus) from inception until August 2013. We included randomized controlled trials (RCTs) of more than 6 months of duration comparing MHT with no treatment. Pairs of independent reviewers selected trials, assessed risk of bias and extracted data. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using the random-effects model. Results: We included 43 RCTs at moderate risk of bias. Meta-analysis showed no effect on mortality (RR 0.99 [95% CI, 0.94–1.05]), regardless of MHT type or history of preexisting heart disease. No association was found between MHT and cardiac death (RR 1.04 [95% CI 0.87–1.23]) or stroke (RR 1.49 [95% CI 0.95–2.31]). Estrogen plus progesterone use was associated with a likely increase in breast cancer mortality (RR 1.96 [95% CI 0.98–3.94]), whereas estrogen use was not. MHT use was not associated with mortality of other types of cancer. In 5 trials, MHT was likely started at a younger age: 2 RCTs with mean age less than 60 and 3 RCTs with MHT started less than 10 years after menopause. Meta-analysis of these 5 RCTs showed a reduction of mortality with MHT (RR 0.70 [95% CI 0.52–0.95]). Conclusion: The current evidence suggests that MHT does not affect the risk of death from all causes, cardiac death and death from stroke or cancer. These data may be used to support clinical and policy deliberations about the role of MHT in the care of symptomatic postmenopausal women.

SummaryIntroductionThyroid ultrasound (US) is a widely used tool for evaluating thyroid nodules. Various US features have been suggested as predictors of thyroid cancer in children.ObjectiveTo conduct a systematic review and meta‐analysis to assess the diagnostic accuracy of different thyroid US features in detecting thyroid cancer in children.MethodsWe searched multiple online databases for cohort studies that enrolled paediatric patients with thyroid nodules (age <21 years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic measures were pooled across studies using a random effects model.ResultsThe search strategy yielded 1199 citations, of which 12 studies met the predefined inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27·2% (40·8% in patients with a history of radiation exposure and 23·2% in patients without a history of exposure to radiation). The most common cancer was papillary thyroid cancer (86·7%). The presence of internal calcifications and enlarged cervical lymph nodes were the US features with the highest likelihood ratio [4·46 (95% CI: 1·87–10·64) and 4·96 (95% CI: 2·01–12·24), respectively] for thyroid cancer. A cystic nodule was the feature with highest likelihood ratio for benign nodules [1·96 (95% CI: 0·87–4·43)].ConclusionThyroid US features are not highly accurate predictors of benign or malignant aetiology of thyroid nodules in children. Internal calcification may predict malignancy, and cystic appearance may suggest benign aetiology.

Background. Irritable bowel syndrome (IBS) is a poorly understood disease with few effective treatments. Psychosocial factors are believed to contribute to the pathogenesis of IBS.Objective. To evaluate the evidence for psychological therapies in IBS treatment.Methods. We searched six medical databases through February 6, 2014, for randomized controlled trials (RCTs) of psychological therapies for the treatment of IBS. Two independent reviewers identified the RCTs, extracted the data, and assessed trial quality. We used the random-effect model to pool standardized mean difference (SMD) and 95% confidence interval (CI) across trials.Results. 15 RCTs that mostly evaluated cognitive behavioral therapy were included. Psychological therapies were associated with improvement in IBS symptoms severity scales (SMD −0.618; 95% CI: −0.853 to −0.383), IBS-Quality of Life (SMD 0.604; 95% CI: 0.440 to 0.768), and abdominal pain (SMD −0.282; 95% CI: −0.562 to −0.001). No statistically significant effect was observed on diarrhea or constipation.Limitations. The trials were at increased risk of bias and the overall sample size was small leading to imprecision.Conclusion. Psychological therapies may improve the quality of life and symptom severity in IBS. The effect size noted is moderate to large and is clinically meaningful.

AbstractContext:Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms.Objective:We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function.Methods:We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I2 statistic.Results:We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, −0.02 to 0.73; P value = .06; I2 = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs.Conclusions:Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.

SummaryBackgroundThe presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.ObjectiveTo describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.MethodsWe searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.ResultsWe included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.ConclusionsThe frequency of germline mutations in SPPs is approximately 11–13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.

Background Motor vehicle accidents associated with commercial driving are an important cause of occupational death and impact public safety. Objectives We summarise the evidence regarding the type, prevalence and impact of medical conditions discovered during health assessment of commercial drivers. Evidence review We conducted a systematic review of multiple electronic databases and made a manual search for relevant studies that enrolled commercial drivers in any country and reported the outcomes of health assessment carried out in the context of commercial driving through November 2012. Data were extracted by a pair of independent reviewers and synthesised using a metanarrative approach. Results We identified 32 studies of moderate methodological quality enrolling 151 644 commercial drivers (98% men). The prevalence of multiple health conditions was high (sleep disorders 19%, diabetes 33%, hypertension 23% and obesity 45%). Some conditions, such as sleep disorders and obesity, were linked to increased risk of crashes. Evidence on several other highly relevant medical conditions was lacking. Cost-effectiveness data were sparse. Conclusions Several medical conditions are highly prevalent in commercial drivers and can be associated with increased risk of crashes, thus providing a rationale for health assessment of commercial drivers.