BackgroundAlcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects.MethodsMEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses.FindingsWe identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05).InterpretationAD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

Background: Velamentous cord insertion (VCI) is an umbilical cord attachment to the membranes surrounding the placenta instead of the central mass. VCI is strongly associated with vasa praevia (VP), where umbilical vessels lie in close proximity to the internal cervical os. VP leaves the vessels vulnerable to rupture, which can lead to fatal fetal exsanguination. Screening for VP using second-trimester transabdominal sonography (TAS) to detect VCI has been proposed. We conducted a rapid review investigating the quality, quantity and direction of evidence available on the epidemiology, screening test accuracy and post-screening management pathways for VCI. Methods: MEDLINE, Embase and the Cochrane Library were searched on 5 July 2016 and again on 11 October 2019, using general search terms for VP and VCI. Only peer-reviewed articles reporting on the epidemiology of VCI, the accuracy of the screening test and/or downstream management pathways for VCI pregnancies were included. Quality and risk of bias of each included study were assessed using pre-specified tools. Results: Forty-one relevant publications were identified; all but one were based on non-UK pregnancy cohorts, and most included relatively few VCI cases. The estimated incidence of VCI was 0.4-11% in singleton pregnancies, with higher incidence in twin pregnancies (1.6-40%). VCI incidence was also increased among pregnancies with one or more other risk factors, including in vitro fertilisation pregnancies or nulliparity. VCI incidence among women without any known risk factors was unclear. VCI was associated with adverse perinatal outcomes, most notably pre-term birth and emergency caesarean section in singleton pregnancies, and perinatal mortality in twins; however, associations varied across studies and the increased risk was typically low or moderate compared with pregnancies without VCI. In studies on limited numbers of cases, screening for VCI using TAS had good overall accuracy, driven by high specificity. No studies on post-screening management of VCI were identified. Conclusions: Literature on VCI epidemiology and outcomes is limited and low-quality. The accuracy of secondtrimester TAS and the benefits and harms of screening cannot be determined without prospective studies in large cohorts. Modelling studies may indicate the feasibility and value of studying the epidemiology of VCI and the potential impact of detecting VCI as part of a population screening programme for VP.

Despite hyperkalaemia being associated with several chronic diseases, there is a paucity of high-quality randomised evidence on long-established treatment options (SPS and CPS) and a limited evidence base for hyperkalaemia management with these agents.

Background: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. Methods: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. Results: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3–65% and 3–42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266–1,381 versus 67.5–575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791–2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). Conclusions: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.

Background This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a “NASH” subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. Results 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from ¥322,206 to ¥340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. Conclusions There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.