Ahmed, Ahmed T.

One of the most controversial health decisions facing women is deciding upon the use of hormonal treatments for symptoms of menopause. This brief review focuses on the historical context of use of menopausal hormone treatments (MHT), summarizes results of major observational, primary and secondary prevention studies of MHT and cardiovascular (CV) outcomes, provides evidence for how sex steroids modulate CV function and identifies challenges for future research. As medicine enters an era of personalization of treatment options, additional research into sex differences in the aetiology of CV diseases will lead to better risk identification for CV disease in women and identify whether a woman might receive CV benefit from specific formulations and doses of MHT.

Most individuals with chronic hepatitis B viral (HBV) infection acquired the infection around the time of birth or during early childhood. We aimed to synthesize evidence regarding the effectiveness of antiviral therapy in the management of chronic HBV infection in children. We conducted a comprehensive search of multiple databases from 1988 to December 2, 2014, for studies that enrolled children (<18 years) with chronic HBV infection treated with antiviral therapy. We included observational studies and randomized controlled trials (RCTs). Two independent reviewers selected studies and extracted data. In the 14 included studies, two cohort studies showed no significant reduction in the already low risk of hepatocellular carcinoma or cirrhosis and 12 RCTs reported intermediate outcomes. In RCTs with posttreatment follow‐up <12 months, antiviral therapy compared to placebo improved alanine aminotransferase normalization (risk ratio [RR] = 2.3, 95% confidence interval [CI] 1.7‐3.2), hepatitis B e antigen (HBeAg) clearance/loss (RR = 2.1, 95% CI 1.5‐3.1), HBV DNA suppression (RR = 2.9, 95% CI 1.8‐4.6), HBeAg seroconversion (RR = 2.1, 95% CI 1.4‐3.3), and hepatitis B surface antigen clearance (RR = 5.8, 95% CI 1.1‐31.5). In RCTs with posttreatment follow‐up ≥12 months, antiviral therapy improved cumulative HBeAg clearance/loss (RR = 1.9, 95% CI 1.7‐3.1), HBeAg seroconversion (RR = 2.1, 95% CI 1.3‐3.5), alanine aminotransferase normalization (RR = 1.4, 95% CI 1.1‐1.7), and HBV DNA suppression (RR = 1.4, 95% CI 1.1‐1.8) but not hepatitis B surface antigen clearance or seroconversion. Conclusion: In children with chronic HBV infection, antivirals compared to no antiviral therapy improve HBV DNA suppression and frequency of alanine aminotransferase normalization and HBeAg seroconversion. (Hepatology 2016;63:307–318)

Perinatal or mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta‐analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.5) at 6‐12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4‐8 weeks' postpartum follow‐up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. Conclusions: Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome. (Hepatology 2016;63:319–333)

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 phrase ‘Initial Clinical Experience' in a manuscript's title implies that the described technique offers promise of future clinical relevance. We assessed, using rates of subsequent citations, the actual academic relevance of such articles in comparison to articles not containing the phrase. Design We searched ISI database for articles that included the studied phrase in their titles between 1975 and 2009 and grouped the results by the related medical specialty. We excluded articles from journals with no available impact factor. For each identified article, we extracted number of included patients, citations/year, the average impact factor of the publishing journal over the last five years and the proportion of articles published in the same journal that garnered zero subsequent citations. Setting Retrospective review of a scientific database. Participants None Main outcome measures Citation rate Results Among a total of 982,127 articles published in 186 journals representing eight major publishing medical specialties, 531 (0.05%) were Initial Clinical Experience articles. Thirty percent of Initial Clinical Experience articles were never cited compared with 7% of the overall article volume ( p < 0.0001). Citations/year for Initial Clinical Experience articles were significantly lower than the median impact factor ( p < 0.0001). There was no correlation between citations and number of patients described in the Initial Clinical Experience articles ( p = 0.61). Conclusions Initial Clinical Experience articles are cited less frequently than the average, especially in Cardiovascular, Radiology and Ophthalmology journals.