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Aims: Heart failure (HF) is a global health burden and new strategies to achieve timely diagnosis and early intervention are urgently needed. Natriuretic peptide (NP) testing can be used to screen for left ventricular systolic dysfunction (LVSD), but evidence on test performance is mixed, and international HF guidelines differ in their recommendations. Our aim was to summarize the evidence on diagnostic accuracy of NP screening for LVSD in general and high‐risk community populations and estimate optimal screening thresholds. Methods: We searched relevant databases up to August 2020 for studies with a screened community population of over 100 adults reporting NP performance to diagnose LVSD. Study inclusion, quality assessment, and data extraction were conducted independently and in duplicate. Diagnostic test meta‐analysis used hierarchical summary receiver operating characteristic curves to obtain estimates of pooled accuracy to detect LVSD, with optimal thresholds obtained to maximize the sum of sensitivity and specificity. Results: Twenty‐four studies were identified, involving 26 565 participants: eight studies in high‐risk populations (at least one cardiovascular risk factor), 12 studies in general populations, and four in both high‐risk and general populations combined. For detecting LVSD in screened high‐risk populations with N‐terminal prohormone brain natriuretic peptide (NT‐proBNP), the pooled sensitivity was 0.87 [95% confidence interval (CI) 0.73–0.94] and specificity 0.84 (95% CI 0.55–0.96); for BNP, sensitivity was 0.75 (95% CI 0.65–0.83) and specificity 0.78 (95% CI 0.72–0.84). Heterogeneity between studies was high with variations in positivity threshold. Due to a paucity of high‐risk studies that assessed NP performance at multiple thresholds, it was not possible to calculate optimal thresholds for LVSD screening in high‐risk populations alone. To provide an indication of where the positivity threshold might lie, the pooled accuracy for LVSD screening in high‐risk and general community populations were combined and gave an optimal cut‐off of 311 pg/mL [sensitivity 0.74 (95% CI 0.53–0.88), specificity 0.85 (95% CI 0.68–0.93)] for NT‐proBNP and 49 pg/mL [sensitivity 0.68 (95% CI 0.45–0.85), specificity 0.81 (0.67–0.90)] for BNP. Conclusions: Our findings suggest that in high‐risk community populations NP screening may accurately detect LVSD, potentially providing an important opportunity for diagnosis and early intervention. Our study highlights an urgent need for further prospective studies, as well as an individual participant data meta‐analysis, to more precisely evaluate diagnostic accuracy and identify optimal screening thresholds in specifically defined community‐based populations to inform future guideline recommendations. [ABSTRACT FROM AUTHOR]

Aims: To investigate the comparative and combined effectiveness of four types of components of behavioural interventions for cigarette smoking cessation: behavioural (e.g. counselling), motivational (e.g. focus on reasons to quit), delivery mode (e.g. phone) and provider (e.g. nurse). Design Systematic review and component network meta‐analysis of randomised controlled trials identified from Cochrane reviews. Interventions included behavioural interventions for smoking cessation (including all non‐pharmacological interventions, e.g. counselling, exercise, hypnotherapy, self‐help materials), compared with another behavioural intervention or no support. Building on a 2021 review (CD013229), we conducted three analyses, investigating: comparative effectiveness of the components, whether models that allowed interactions between components gave different results to models assuming additivity, and predicted effect estimates for combined effects of components that had showed promise but where there were few trials. Setting: Community and health‐care settings. Participants: Adults who smoke tobacco. Measurements Smoking cessation at ≥6 months, preferring sustained, biochemically validated outcomes where available. Findings Three hundred and twelve trials (250 563 participants) were included. Fifty were at high risk of bias using Cochrane risk of bias tool, V1 (ROB1); excluding these studies did not change findings. Head‐to‐head comparisons of components suggested that support via text message (SMS) compared with telephone (OR 1.48, 95% CrI 1.13–1.94) or print materials (OR 1.44, 95% CrI 1.14–1.83) was more effective, and individual delivery was less effective than delivery as part of a group (OR 0.78, 95% CrI 0.64–0.95). There was no conclusive evidence of synergistic or antagonistic interactions when combining components that were commonly used together. Adding multiple components that are commonly used in behavioural counselling suggested clinically relevant and statistically conclusive evidence of benefit. Components with the largest effects that could be combined, but rarely have been, were estimated to increase the odds of quitting between two and threefold. For example, financial incentives delivered via SMS, with tailoring and a focus on how to quit, had an estimated OR of 2.94 (95% CrI 1.91–4.52). Conclusions: Among the components of behavioural support for smoking cessation, behavioural counselling and guaranteed financial incentives are associated with the greatest success. Incorporating additional components associated with effectiveness may further increase benefit, with delivery via text message showing particular promise. [ABSTRACT FROM AUTHOR]

Psychological models of bipolar disorder (BD), such as the self‐regulation model (SRM; Leventhal, Nerenz, & Steele, 1984), highlight the crucial role of beliefs about mood in relapse vulnerability. To date, no studies have directly compared these beliefs between people with and without BD. Based on the SRM, the current research examined beliefs about mood in people with and without BD and explored the impact of current affect on these beliefs. Fifty euthymic people with a diagnosis of BD and 50 controls were recruited through an online screening study, clinical services, and support organizations. Experience sampling methodology (ESM) was used to assess beliefs (according to the Brief Illness Perceptions Questionnaire; Broadbent, Petrie, Main, & Weinman, 2006) across a typical week of everyday life. Data were analysed using multilevel modelling. Forty‐two people with a diagnosis of BD and 50 controls were included in the analyses. Results indicated that the BD group reported less control over mood, a shorter duration of mood, and less understanding of mood and were more likely to report the cause of depressive symptoms as something internal, compared with controls. When controlling for current affect, the BD group also reported more positive consequences, made more internal attributions for hypomanic symptoms, and reported less concern about mood, compared with controls. Findings suggest important differences in beliefs about mood between people with and without BD that are not the result of current affect. These beliefs may be particularly important in understanding underlying vulnerability to future relapse into depression and/or mania. [ABSTRACT FROM AUTHOR]

Introduction Previous studies suggest that many systematic reviews contain meta-analyses that display temporal trends, such as the first study's result being more extreme than later studies' or a drift in the pooled estimate. We assessed the extent and characteristics of temporal trends using all Cochrane intervention reports published 2008-2012. Methods We selected the largest meta-analysis within each report and analysed trends using methods including a Z-test (first versus subsequent estimates); generalised least squares; and cumulative sum charts. Predictors considered include meta-analysis size and review group. Results Of 1288 meta-analyses containing at least 4 studies, the point estimate from the first study was more extreme and in the same direction as the pooled estimate in 738 (57%), with a statistically significant difference (first versus subsequent) in 165 (13%). Generalised least squares indicated trends in 717 (56%); 18% of fixed effects analyses had at least one violation of cumulative sum limits. For some methods, meta-analysis size was associated with temporal patterns and use of a random effects model, but there was no consistent association with review group. Conclusions All results suggest that more meta-analyses demonstrate temporal patterns than would be expected by chance. Hence, assuming the standard meta-analysis model without temporal trend is sometimes inappropriate. Factors associated with trends are likely to be context specific. [ABSTRACT FROM AUTHOR]

As evidence accumulates within a meta-analysis, it is desirable to determine when the results could be considered conclusive to guide systematic review updates and future trial designs. Adapting sequential testing methodology from clinical trials for application to pooled meta-analytic effect size estimates appears well suited for this objective. In this paper, we describe a Bayesian sequential meta-analysis method, in which an informative heterogeneity prior is employed and stopping rule criteria are applied directly to the posterior distribution for the treatment effect parameter. Using simulation studies, we examine how well this approach performs under different parameter combinations by monitoring the proportion of sequential meta-analyses that reach incorrect conclusions (to yield error rates), the number of studies required to reach conclusion, and the resulting parameter estimates. By adjusting the stopping rule thresholds, the overall error rates can be controlled within the target levels and are no higher than those of alternative frequentist and semi-Bayes methods for the majority of the simulation scenarios. To illustrate the potential application of this method, we consider two contrasting meta-analyses using data from the Cochrane Library and compare the results of employing different sequential methods while examining the effect of the heterogeneity prior in the proposed Bayesian approach. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions. Methods: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted. Results: The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression ( P=0.006), from RN to HCC; this trend was not statistically significant for geminin ( P=0.18) or MCM2 ( P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: ‘resting’ (G0 cells: MCM2 −ve, Ki67 −ve, geminin −ve); ‘licensed’ (MCM2 +ve, Ki67 −ve, geminin −ve); ‘slowly growing’ (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules. Conclusions: The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis. [ABSTRACT FROM AUTHOR]