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Objective. To evaluate the validity, in terms of the patients’ acceptance, preference, feasibility and reliability of an innovative, interactive computerized system for collection of patient-reported outcome (PRO) data on axial SpA against the paper-and-pencil version.Methods. Fifty-five patients with axial SpA completed both the touch screen and the paper-and-pencil set of questionnaires. A computerized touch-screen system, SPEAMonitor, was developed to capture PRO data. Variables recorded included demographic data, patient’s assessment of general health status, BASDAI, BASFI, BASMI and acute-phase reactant levels. In order to assess the patient’s acceptance of, preference for and feasibility of computer-based questionnaires, the participants filled in an additional questionnaire. The time taken to complete both formats was measured. In a further test–retest study, 25 patients were re-evaluated.Results. The agreement between the paper-administered and computer touch-screen format of the BASFI, BASDAI questionnaires and the Ankylosing Spondylitis Disease Activity Scores was excellent. Intraclass correlation coefficients (ICCs) between data ranged from 0.90 to 0.96. Additionally the test–retest study showed a very good agreement between the scores for the two administrations (ICC ≥ 0.90). Age, computer experience and education level had no significant impact on the results. The computerized questionnaires were reported to be easier to use. The mean time spent completing the questionnaires on a touch screen was 5.1 min and on paper 7.9 min.Conclusion. Our newly developed computer-assisted touch-screen questionnaires for PRO in axial SpA were well accepted by patients, with good data quality, reliability and score agreement. [ABSTRACT FROM PUBLISHER]

Biostatistics plays a pivotal role in developing, interpreting and drawing conclusions from clinical, biological and epidemiological data. However, the improper application of statistical methods can lead to erroneous conclusions and misinterpretations. This paper provides a comprehensive examination of the most frequent mistakes encountered in the biostatistical analysis process. We identified and elucidated 10 common errors in biostatistical analysis. These include using the wrong metric to describe data, misinterpreting P -values, misinterpreting the 95% confidence interval, misinterpreting the hazard ratio as an index of prognostic accuracy, ignoring the sample size calculation, misinterpreting analysis by strata in randomized clinical trials, confusing correlation and causation, misunderstanding confounders and mediators, inadequately codifying variables during the data collection, and bias arising when group membership is attributed on the basis of future exposure in retrospective studies. We discuss the implications of these errors and propose some practical strategies to mitigate their impact. By raising awareness of these pitfalls, this paper aims to enhance the rigor and reproducibility of biostatistical analyses, thereby fostering more robust and reliable biomedical research findings. [ABSTRACT FROM AUTHOR]

Background Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies appear to show little to no association between aspirin use and breast cancer mortality, all-cause mortality, or recurrence. Aims This study aims to conduct an updated systematic review and meta-analysis on the associations of pre-diagnostic and post-diagnostic aspirin use with the aforementioned breast cancer outcomes. It also looks, through subgroup analyses and meta-regressions, at a range of variables that could explain the associations between aspirin use and breast cancer outcomes. Results In total, 24 papers and 149 860 patients with breast cancer were included. Pre-diagnostic aspirin use was not associated with breast-cancer-specific mortality (HR 0.98, 95% CI, 0.80-1.20, P =.84) or recurrence (HR 0.94, 95% CI, 0.88-1.02, P =.13). Pre-diagnostic aspirin was associated with non-significantly higher all-cause mortality (HR 1.27, 95% CI, 0.95-1.72, P =.11). Post-diagnostic aspirin was not significantly associated with all-cause mortality (HR 0.87, 95% CI, 0.71-1.07, P =.18) or recurrence (HR 0.89, 95% CI, 0.67-1.16, P =.38). Post-diagnostic aspirin use was significantly associated with lower breast-cancer-specific mortality (HR 0.79, 95% CI, 0.64-0.98, P =.032). Conclusions The only significant association of aspirin with breast cancer outcomes is lower breast-cancer-specific mortality in patients who used aspirin post-diagnostically. However, factors such as selection bias and high inter-study heterogeneity mean that this result should not be treated as conclusive, and more substantial evidence such as that provided by RCTs is needed before any decisions on new clinical uses for aspirin should be made. [ABSTRACT FROM AUTHOR]

Interaction analysis is a critical component of clinical and public health research and represents a key topic in precision health and medicine. In applied settings, however, interaction assessment is usually limited to the test of a product term in a regression model and to the presentation of results stratified by levels of additional covariates. Stratification of results often relies on categorizing or making linearity assumptions for continuous covariates, with substantial loss of precision and of relevant information. In time-to-event analysis, moreover, interaction assessment is often limited to the multiplicative hazard scale by inclusion of a product term in a Cox regression model, disregarding the clinically relevant information that is captured by the absolute risk scale. In this paper we present a user-friendly procedure, based on the prediction of individual absolute risks from the Cox model, for the estimation and presentation of interactive effects on both the multiplicative and additive scales in survival analysis. We describe how to flexibly incorporate interactions with continuous covariates, which potentially operate in a nonlinear fashion, provide software for replicating our procedure, and discuss different approaches to deriving CIs. The presented approach will allow clinical and public health researchers to assess complex relationships between multiple covariates as they relate to a clinical endpoint, and to provide a more intuitive and precise depiction of the results in applied research papers focusing on interaction and effect stratification. [ABSTRACT FROM AUTHOR]

Objective: To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. Methods: We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. Results: The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4ºC and as many as 14 days at -70ºC. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. Conclusion: We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. [ABSTRACT FROM AUTHOR]

Objective Utilities are values of health-related quality of life (HRQoL) based on patient preference for a health status. The purpose of this study was to compare indirect measures to a directly elicited utility. Design Cross-sectional study. Setting and Patients Emory Spine Center and the Emory Center for Chronic Pain at Crawford Long Hospital. Patients at least 18 years of age with chronic pain, defined as pain that persists beyond the normal time of healing, usually beyond 6 months. Measures Chronic pain subjects completed a paper-based, self-administered time trade-off ( TTO) survey, EQ-5 D survey, and a face-to-face ( FTF) TTO interview. Current pain severity was graded using the Numeric Rating Scale-11, subsequently stratified into no (0), mild (1-3), moderate (4-6), and severe (7-10) pain. Results Paired t test comparing FTF TTO and proxy utility measures stratified by severity revealed FTF TTO utility values significantly higher than EQ-5 D utility values for all pain severities (overall mean difference 0.18, standard deviation [ SD] 0.30, P < 0.001; Pearson's correlation 0.34, P < 0.0001); FTF TTO utility values were lower than paper TTO utility values, reaching statistical significance for mild and moderate pain (overall mean difference 0.09, SD 0.29, P = 0.0006; Pearson's correlation 0.38, P < 0.0001). Conclusions This study demonstrates that the EQ-5 D overestimates, whereas the paper version of TTO underestimates, the impact of pain on HRQoL compared with the directly elicited FTF TTO utility. Our findings provide preliminary evidence that utilities vary by method, and directly elicited utility values differ from indirectly elicited measures. [ABSTRACT FROM AUTHOR]

Background. Disparity between patient report and physician perception of pain from radiotracer injection for sentinel node biopsy is thought to center on the severity of the intervention, ethnic composition of population queried, and socioeconomic factors. Objective. The objectives of this study were, first, to explore agreement between physicians' and their breast cancer patients' pain assessment during subareolar radionucleotide injection; and second, to evaluate potential ethnic differences in ratings. Methods. A trial was conducted, from January 2006 to April 2009, where 140 breast cancer patients were randomly assigned to standard topical lidocaine-4% cream and 99mTc-sulfur colloid injection, or to one of three other groups: placebo cream and 99mTc-sulfur colloid injection containing NaHCO3, 1% lidocaine, or NaHCO3 + 1% lidocaine. Providers and patients completed numeric pain scales (0-10) immediately after injection. Results. Patients and providers rated pain similarly over the entire cohort (median, 3 vs 2, P = 0.15). Patients rated pain statistically significantly higher than physicians in the standard (6 vs 5, P = 0.045) and placebo + NaHCO3 (5 vs 4, P = 0.032) groups. No significant difference in scores existed between all African Americans and their physicians (3 vs 4, P = 0.27). Conclusion. Patient-physician pain assessment congruence over the less painful injections and their statistically similar scores with the more painful methods suggests the importance of utilizing the least painful method possible. Providers tended to underestimate patients with the highest pain ratings-those in the greatest analgesic need. Lack of statistical difference between African American and physician scores may reflect the equal-access-to-care over the entire patient cohort, supporting the conclusion that socioeconomic factors may lie at the heart of previously reported discrepancies. [ABSTRACT FROM AUTHOR]

Objectives The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC). Methods Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774). Results Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P  = 0.0034; I 2 = 71%, Q 2 P  = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P  = 0.045; I 2 = 39%, Q 2 P  = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P  = 0.01; I 2 = 61%, Q 2 P  = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P  < 0.001; I 2 = 10%, Q 2 P  = 0.34) in fibromyalgia patients compared with HC. Conclusion We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia. [ABSTRACT FROM AUTHOR]

Background Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (B Cs) embedded within antimicrobial stewardship programs (ASPs) is unknown. Methods We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. Results Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI],.59–.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI,.63–.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI,.84–.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (−29 hours; 95% CI, −35 to −23), BC + ASP (−18 hours; 95% CI, −27 to −10), and to RDT alone (−12 hours; 95% CI, −20 to −3). Conclusions The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC. [ABSTRACT FROM AUTHOR]

Family group conferences (FGCs) in child welfare share decision-making with family members by bringing the immediate and wider family together to make a plan to meet a child's needs. This paper reports survey findings on FGC provision in the UK in 2022 and explores whether in England the presence of an FGC service and the rate of FGC provision is associated with the rate of children in care, entering care, in kinship foster care and leaving care. Seventy-nine per cent (n  = 167) of local authorities in the UK provided FGCs to families, and 14 per cent (n  = 29) did not. Services that were more established offered a more diverse range of FGCs. The introduction of FGCs in English local authorities was associated with a higher rate of children in care, but also higher rates of kinship foster care, a key goal of FGCs where it is not possible for children to stay with their parents. Higher rates of FGCs were associated with more children leaving care, possibly due to reunification with birth families. To understand in more detail, the circumstances of children in and leaving care in local authorities with FGCs, individual data linkage studies are needed. [ABSTRACT FROM AUTHOR]

Background and objectives This paper describes an evaluation and analysis of an updated version of ECEL v3.0—an integrated risk management measure (RMM) library developed as part of a CEFIC LRI initiative. The occupational module contains extensive data on the quantitative effectiveness of RMMs to control inhalation and dermal exposure in the workplace. The objective was to investigate the effectiveness and variability in effectiveness of RMM and to explore the difference between optimal and non-optimal RMM applications in the workplace. Methods A new database structure and interface were developed and the content of the database was updated with a systematic literature review and integration with other databases (totalling 3373 records from 548 studies). To analyse the data, Bayesian linear mixed models were constructed with the study as a random effect and various study characteristics and RMM categories as fixed effects individually in separate models. A multivariate mixed model was used on a stratified dataset to test (amongst others) the conditions of RMM use. Results Analyses of the data indicated effectiveness values for each RMM category (for example ~87% for technical emission controls compared with ~60% for technical dispersion controls). Substantial variability in effectiveness was observed within and between different types of RMM. Seven study characteristics (covariables) were included in the analyses, which indicated a pronounced difference in as-built (optimal/experimental) and as-used (workplace) conditions of RMM use (93.3% and 74.6%, respectively). Conclusions This library provides a reliable evidence base to derive base estimates of RMM effectiveness—beneficial for both registrant and downstream users. It stresses the importance of optimal use of RMMs in the workplace (technical design/functioning, use, and maintenance). Various challenges are foreseen to further update ECEL to improve guidance, for deriving improved estimates and ensure user-friendliness of the library. [ABSTRACT FROM AUTHOR]

Background Declines in cardiorespiratory fitness (CRF) and muscle mass are both associated with advancing age and each of these declines is associated with worse health outcomes. Resistance exercise training (RET) has previously been shown to improve muscle mass and function in the older population. If RET is also able to improve CRF, as it has been shown to do in younger populations, it has the potential to improve multiple health outcomes in the expanding older population. Methods This systematic review aimed to identify the role of RET for improving CRF in healthy older adults. A search across CINAHL, MEDLINE, EMBASE and EMCARE databases was conducted with meta-analysis performed on eligible papers to identify improvements in established CRF parameters (VO2 peak, aerobic threshold (AT), 6-minute walking distance test (6MWT) following RET intervention. Main eligibility criteria included older adults (aged over 60), healthy cohorts (disease-specific cohorts were excluded) and RET intervention. Results Thirty-seven eligible studies were identified. Meta-analysis revealed a significant improvement in VO2 peak (MD 1.89 ml/kg/min; 95% confidence interval (CI) 1.21–2.57 ml/kg/min), AT (MD 1.27 ml/kg/min; 95% CI 0.44–2.09 ml/kg/min) and 6MWT (MD 30.89; 95% CI 26.7–35.08) in RET interventions less than 24 weeks. There was no difference in VO2 peak or 6MWT in interventions longer than 24 weeks. Discussion This systematic review adds to a growing body of evidence supporting the implementation of RET in the older population for improving whole-body health, particularly in time-limited timeframes. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa (SSA), cervical cancer (CC) is the second leading cause of cancer-related deaths, with human immunodeficiency virus (HIV) seropositive women being particularly vulnerable. Despite the benefits of early CC screening in reducing HIV-related CC deaths, CC screening uptake remains limited, with wide disparities in access across SSA. As part of a larger study, this paper examines the determinants of CC screening among HIV-seropositive women of reproductive age (15–49 years) in Zimbabwe. Using the 2015 Zimbabwe Demographic and Health Survey, we conducted multilevel analyses of CC screening among 1490 HIV-seropositive women, nested in 400 clusters. Our findings revealed that, even though 74% of HIV-seropositive women knew about CC, only 17.6% of them reported ever screening for it. Women who held misconceptions about HIV (OR = 0.47, p = 0.01) were less likely to screen for CC compared to those with accurate knowledge about HIV and CC. HIV-seropositive women with secondary or higher education were more likely to screen (OR = 1.39, p = 0.04) for CC compared to those with a primary or lower level of education. Age was positively associated with screening for CC. Furthermore, locational factors, including province and rural–urban residence, were associated with CC screening. Based on these findings, we call for integrated care and management of HIV and non-communicable diseases in Southern Africa, specifically, Zimbabwe due to the legacy of HIV in the region. [ABSTRACT FROM AUTHOR]

Aims The outbreak of COVID-19 was potentially stressful for everyone and possibly heightened in those having surgery. We sought to explore the impact of the pandemic on recovery from cardiac surgery. Methods and results A prospective observational study of 196 patients who were ≥18years old undergoing cardiac surgery between March 23 and July 4, 2020 (UK lockdown) was conducted. Those too unwell or unable to give consent/complete the questionnaires were excluded. Participants completed (on paper or electronically) the impact of event [Impact of Events Scale-revised (IES-R)] (distress related to COVID-19), depression [Centre for Epidemiological Studies Depression Scale (CES-D)], and EQ-5D-5L [(quality of life, health-related quality of life (HRQoL)] questionnaires at baseline, 1 week after hospital discharge, and 6 weeks, 6 months and 1 year post-surgery. Questionnaire completion was >75.0% at all timepoints, except at 1 week (67.3%). Most participants were male [147 (75.0%)], white British [156 (79.6%)] with an average age 63.4years. No patients had COVID-19. IES-R sand CES-D were above average at baseline (indicating higher levels of anxiety and depression) decreasing over time. HRQoL pre-surgery was high, reducing at 1 week but increasing to almost pre-operative levels at 6 weeks and exceeding pre-operative levels at 6 months and 1 year. IES-R and CES-D scores were consistently higher in women and younger patients with women also having poorer HRQoL up to 1-year after surgery. Conclusions High levels of distress were observed in patients undergoing cardiac surgery during the COVID-19 pandemic with women and younger participants particularly affected. Psychological support pre- and post-operatively in further crises or traumatic times should be considered to aid recovery. Registration Clinicaltrials.gov ID:NCT04366167. [ABSTRACT FROM AUTHOR]

Instrumental variable methods are among the most commonly used causal inference approaches to deal with unmeasured confounders in observational studies. The presence of invalid instruments is the primary concern for practical applications, and a fast-growing area of research is inference for the causal effect with possibly invalid instruments. This paper illustrates that the existing confidence intervals may undercover when the valid and invalid instruments are hard to separate in a data-dependent way. To address this, we construct uniformly valid confidence intervals that are robust to the mistakes in separating valid and invalid instruments. We propose to search for a range of treatment effect values that lead to sufficiently many valid instruments. We further devise a novel sampling method, which, together with searching, leads to a more precise confidence interval. Our proposed searching and sampling confidence intervals are uniformly valid and achieve the parametric length under the finite-sample majority and plurality rules. We apply our proposal to examine the effect of education on earnings. The proposed method is implemented in the R package R o b u s t I V available from CRAN. [ABSTRACT FROM AUTHOR]

The Bradley–Terry–Luce (BTL) model is a benchmark model for pairwise comparisons between individuals. Despite recent progress on the first-order asymptotics of several popular procedures, the understanding of uncertainty quantification in the BTL model remains largely incomplete, especially when the underlying comparison graph is sparse. In this paper, we fill this gap by focusing on two estimators that have received much recent attention: the maximum likelihood estimator (MLE) and the spectral estimator. Using a unified proof strategy, we derive sharp and uniform non-asymptotic expansions for both estimators in the sparsest possible regime (up to some poly-logarithmic factors) of the underlying comparison graph. These expansions allow us to obtain: (i) finite-dimensional central limit theorems for both estimators; (ii) construction of confidence intervals for individual ranks; (iii) optimal constant of |$\ell _2$| estimation, which is achieved by the MLE but not by the spectral estimator. Our proof is based on a self-consistent equation of the second-order remainder vector and a novel leave-two-out analysis. [ABSTRACT FROM AUTHOR]

Background frailty is common in older adults and associated with poor outcomes following illness. Although stroke is predominantly a disease of older people, our knowledge of frailty in stroke is limited. We aimed to collate the literature on acute stroke and frailty to estimate the prevalence of pre-stroke frailty and its associations with outcomes. Methods paired researchers searched multidisciplinary electronic databases for papers describing frailty and acute stroke. We assessed risk of bias using Newcastle-Ottawa tools appropriate to study design. We created summary estimates of pre-stroke frailty using random effects models. We collated whether studies reported significant positive associations between frailty and clinical outcomes in adjusted models. Results we included 14 studies (n  = 27,210 participants). Seven studies (n  = 8,840) used a frailty index approach, four studies (n  = 14,924) used Hospital Frailty Risk Scores. Pooled prevalence of pre-stroke frailty was 24.6% (95% confidence interval, CI: 16.2–33.1%; low quality evidence, downgraded due to heterogeneity, bias). Combining frailty and pre-frailty (nine studies, n  = 23,827), prevalence of any frailty syndrome was 66.8% (95%CI: 49.9–83.7%). Seven studies were at risk of bias, from participant selection or method of frailty assessment. Pre-stroke frailty was associated with all adverse outcomes assessed, including longer-term mortality (positive association in 6 of 6 studies reporting this outcome; odds ratio: 3.75 [95%CI: 2.41–5.70]), length of admission (3 of 4 studies) and disability (4 of 6 studies). Conclusions despite substantial heterogeneity, whichever way it is measured, frailty is common in patients presenting with acute stroke and associated with poor outcomes. This has implications for the design of stroke services and pathways. [ABSTRACT FROM AUTHOR]

In this paper, we present a practical approach for computing the sandwich variance estimator in 2-stage regression model settings. As a motivating example for 2-stage regression, we consider regression calibration, a popular approach for addressing covariate measurement error. The sandwich variance approach has rarely been applied in regression calibration, despite its requiring less computation time than popular resampling approaches for variance estimation, specifically the bootstrap. This is probably because it requires specialized statistical coding. Here we first outline the steps needed to compute the sandwich variance estimator. We then develop a convenient method of computation in R for sandwich variance estimation, which leverages standard regression model outputs and existing R functions and can be applied in the case of a simple random sample or complex survey design. We use a simulation study to compare the sandwich estimator to a resampling variance approach for both settings. Finally, we further compare these 2 variance estimation approaches in data examples from the Women's Health Initiative (1993–2005) and the Hispanic Community Health Study/Study of Latinos (2008–2011). In our simulations, the sandwich variance estimator typically had good numerical performance, but simple Wald bootstrap confidence intervals were unstable or overcovered in certain settings, particularly when there was high correlation between covariates or large measurement error. [ABSTRACT FROM AUTHOR]

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P  = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P  = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P  = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this. [ABSTRACT FROM AUTHOR]

We have performed targeted searches of known extragalactic transient events at millimetre wavelengths using nine seasons (2013–2021) of 98, 150, and 229 GHz Atacama Cosmology Telescope (ACT) observations that mapped ∼40 per cent of the sky for most of the data volume. Our data cover 88 gamma-ray bursts (GRBs), 12 tidal disruption events (TDEs), and 203 other transients, including supernovae (SNe). We stack our ACT observations to increase the signal-to-noise ratio of the maps. In all cases but one, we do not detect these transients in the ACT data. The single candidate detection (event AT2019ppm), seen at ∼5σ significance in our data, appears to be due to active galactic nuclei activity in the host galaxy coincident with a transient alert. For each source in our search we provide flux upper limits. For example, the medians for the 95 per cent confidence upper limits at 98 GHz are 15, 18, and 16 mJy for GRBs, SNe, and TDEs, respectively, in the first month after discovery. The projected sensitivity of future wide-area cosmic microwave background surveys should be sufficient to detect many of these events using the methods described in this paper. [ABSTRACT FROM AUTHOR]

The Gini index is a popular inequality measure with many applications in social and economic studies. This paper studies semi-parametric inference on the Gini indices of two semi-continuous populations. We characterise the distribution of each semi-continuous population by a mixture of a discrete point mass at zero and a continuous skewed positive component. A semi-parametric density ratio model is then employed to link the positive components of the two distributions. We propose the maximum empirical likelihood estimators of the two Gini indices and their difference, and further investigate the asymptotic properties of the proposed estimators. The asymptotic results enable us to construct confidence intervals, and perform hypothesis tests for the two Gini indices and their difference. The proposed method is also applicable to cases without excessive zero values. The superiority of our proposed method over some existing methods is shown theoretically and numerically. Two real-data applications are presented for illustration. [ABSTRACT FROM AUTHOR]

High-dimensional linear models with independent errors have been well-studied. However, statistical inference on a high-dimensional linear model with heteroskedastic, dependent (and possibly nonstationary) errors is still a novel topic. Under such complex assumptions, the paper at hand introduces a debiased and thresholded ridge regression estimator that is consistent, and is able to recover the model sparsity. Moreover, we derive a Gaussian approximation theorem for the estimator, and apply a dependent wild bootstrap algorithm to construct simultaneous confidence interval and hypothesis tests for linear combinations of parameters. Numerical experiments with both real and simulated data show that the proposed estimator has good finite sample performance. Of independent interest is the development of a new class of heteroscedastic, (weakly) dependent, and nonstationary random variables that can be used as a general model for regression errors. [ABSTRACT FROM AUTHOR]

Background The aim of this paper is to examine the link between severity in exposure to parental problem drinking in a Swedish national population sample of children aged 15–16 years. Specifically, we assessed whether the risk of poor health, poor relationships and a problematic school situation increase with severity in exposure to parental problem drinking. Methods National population survey from 2017 with a representative sample of 5 576 adolescents born in 2001. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CIs). A short version of The Children of Alcoholics Screening Test, CAST-6, was used to identify children with problem-drinking parents. Health status, social relations and school situation were assessed by well-established measures. Results The risk of having poor health, poor school performance and poor social relations increased with severity of parental problem drinking. The risk was lowest among children least severely affected (Crude models ranged from OR: 1.2, 95% CI 1.0–1.4 to OR: 2.2, 95% CI 1.8–2.6) and highest among children most severely affected (Crude models ranges from OR: 1.7, 95% CI 1.3–2.1 to OR: 6.6, 95% CI 5.1–8.6). The risk became lower when adjusting for gender and socioeconomic position but were still higher compared to children without problem-drinking parents. Conclusions Appropriate screening and intervention programs are necessary for children with problem-drinking parents especially when exposure is severe but also at mild forms of exposure. [ABSTRACT FROM AUTHOR]

Appropriately considering adjustment costs, this paper develops a robust nonparametric framework to analyse profits, prices and productivity in a dynamic context. Dynamic profit change is decomposed into a dynamic Bennet price indicator and a dynamic Bennet quantity indicator. The latter is decomposed into explanatory factors. It is shown to be a superlative indicator for the dynamic Luenberger indicator. The application focuses on 1,638 observations of French meat-processing firms for the years 2012–2019. Using m -out-of- n bootstrapped data envelopment analysis, we obtain robust estimates and confidence intervals. The components of dynamic productivity growth fluctuate substantially. However, these fluctuations are often statistically insignificant. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest that metformin use may be associated with improved infectious disease–related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. Methods We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002–2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. Results We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P <.003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P <.0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]:.86; 95% confidence interval [CI]:.78–.95) and 90-day (RR:.85; 95% CI:.79–.92) mortality was significantly lower for metformin users. Conclusions Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections. [ABSTRACT FROM AUTHOR]

"Fusion" study designs combine data from different sources to answer questions that could not be answered (as well) by subsets of the data. Studies that augment main study data with validation data, as in measurement-error correction studies or generalizability studies, are examples of fusion designs. Fusion estimators, here solutions to stacked estimating functions, produce consistent answers to identified research questions using data from fusion designs. In this paper, we describe a pair of examples of fusion designs and estimators, one where we generalize a proportion to a target population and one where we correct measurement error in a proportion. For each case, we present an example motivated by human immunodeficiency virus research and summarize results from simulation studies. Simulations demonstrate that the fusion estimators provide approximately unbiased results with appropriate 95% confidence interval coverage. Fusion estimators can be used to appropriately combine data in answering important questions that benefit from multiple sources of information. [ABSTRACT FROM AUTHOR]

The screening method provides a simple and rapid way of estimating vaccine effectiveness. This paper discusses the validity of the screening method with particular reference to bias and precision. Methods for correcting confounding, adjusting for covariates and over-dispersion, and deriving confidence limits are discussed in a modelling framework. The methods are illustrated using data on measles and pertussis vaccines. [ABSTRACT FROM AUTHOR]

Background Glioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM. Materials and Methods A total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Results The median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P  = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P   =  .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P   =  .001; median OS: 20.2 vs 13.8 months, P   =  .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups. Conclusion Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability. [ABSTRACT FROM AUTHOR]

The frailty index (FI) quantifies frailty as deficit accumulation. It has been adapted to employ laboratory test data (FI-Lab). Our objective was to systematically review and meta-analyse the FI-Lab's ability to predict mortality. Secondary objectives were to review the FI-Lab's association with adverse health outcomes and whether FI-Lab scores differed between the sexes. A systematic literature search was carried out using six online databases to identify studies that measured the FI-Lab in humans. Hazard ratios (HRs) were combined in a meta-analysis to create a pooled risk estimate for mortality. Of the 1,201 papers identified, spanning January 2010 until 11 July 2022, 38 were included. FI-Lab scores per 0.01 unit increase predicted mortality overall (HR = 1.04; 95% confidence interval (CI) = 1.03–1.05) and for studies with a mean age of 81+ years (HR = 1.04; 95% CI = 1.03–1.05). The quality of evidence for these meta-analyses are moderate and high, respectively. Further, higher FI-Lab scores were associated with more frequent adverse health outcomes. Sex differences in FI-Lab scores varied, with no consistent indication of a sex effect. The FI-Lab is associated with mortality and with a variety of adverse health outcomes. No consistent sex differences in FI-Lab scores were observed, with several studies in disagreement. Notably, these conclusions were most relevant to older (65+ years old) individuals; further evidence in younger people is needed in both clinical and population representative studies. [ABSTRACT FROM AUTHOR]

It is well documented that lower socio-economic status is associated with poorer health outcomes, while health literacy is considered important for improving health. What is less clear, is the extent to which greater health literacy can improve health outcomes among people for whom poverty or financial insecurity are important barriers to health. The paper presents findings from an Australian survey of people living with HIV (PLHIV) (N = 835) in which we explored the relationship between financial insecurity and health outcomes, looking at the extent to which health literacy mediates this relationship. The study drew on a comprehensive definition of health literacy, measuring participant's confidence to communicate with healthcare providers, navigate the health system and take an active stance in relation to their health. Findings showed that financial insecurity was associated with lower health literacy and poorer self-reported physical and mental health. Health literacy mediated 16.2% of the effect of financial insecurity on physical health scores and 16.6% of the effect of financial insecurity on mental health scores. This suggests that programmes which seek to build health literacy among PLHIV may improve health outcomes among PLHIV who are struggling financially. Health literacy programmes are likely to be effective if they build confidence and resourcefulness among people to engage with health information, decision-making and care. [ABSTRACT FROM AUTHOR]

Access to safe drinking water is critical in improving health and well-being. It is estimated that >40% of urban households in Ghana do not have access to safe drinking water. Although the willingness and ability of community members to collectively take local initiatives are essential to curtailing inequities in water access in Ghana, the determinant of collective action is less explored. This paper explores determinants of collective action in water-insecure neighbourhoods and examines how perceived inequities in access to water and trust mediate the relationship between lack of access to water and collective action in urban Ghana. The results show that the urban poor OR = 12.047 (p = 0.000) were more likely to participate in water-related collective action compared to wealthy individuals. Primary decision-makers were 1.696 times more likely to participate in collective (p = 0.02). We also found that perceived inequities OR = 0.381 (p = 0.00) significantly predict participation in collective action to address water insecurity. Water service providers should be subjected to a rigid state-level framework that ensures inclusivity, fairness and justice in their distribution systems. [ABSTRACT FROM AUTHOR]

Background Lowering the strength of alcohol products could lead to less alcohol being bought and drunk. In its prevention White Paper, the UK Government aims to promote a significant increase in the availability of alcohol-free and low-alcohol products by 2025. Methods Through descriptive analysis and ARIMA modelling of >4 million alcohol purchases from 69 803 British households, we study the potential impact of lower strength alcohol products in reducing household purchases of grams of alcohol over 2015–2019. Households are divided into predominantly beer, wine or spirits purchasers. Results Over 5 years, there were decreases in purchases of grams of alcohol within beer amongst beer-purchasing households and increases in purchases of grams of alcohol within wine and spirits amongst, respectively, wine- and spirits-purchasing households. Almost all the changes were due to beer-purchasing households buying less regular strength beer, and wine and spirits-purchasing households buying, respectively, more regular strength wine and spirits, rather than increases in purchases of no- and low-alcohol products. Conclusions In general, lower strength alcohol products have not contributed to British households buying fewer grams of alcohol over the 5-year follow-up period during 2015–2019. [ABSTRACT FROM AUTHOR]

Summary: In international football (soccer), two‐legged knockout ties, with each team playing at home in one leg and the final outcome decided on aggregate, are common. Many players, managers and followers seem to believe in ‘second‐leg home advantage’, i.e. that it is beneficial to play at home on the second leg. A more complex effect than the well‐documented usual home advantage, it is more difficult to identify, and previous statistical studies have not proved conclusive about its actuality. As opposed to previous research, the paper addresses the question from a purely non‐parametric perspective, which is not based on any particular model specification which could orientate the analysis in one or the other direction. Along the way, the paper reviews the well‐known shortcomings of the Wald confidence interval for a proportion, suggests new non‐parametric confidence intervals for conditional probability functions, revisits the problems of bias and bandwidth selection when building confidence intervals in non‐parametric regression and provides a novel bootstrap‐based solution to them. Finally, the new intervals are used when analysing game outcome data for the UEFA (Union of European Football Associations) Champions and Europa Leagues from 2009–2010 to 2014–2015. A slight second‐leg home advantage is evidenced. [ABSTRACT FROM AUTHOR]

Aims: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3–L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. Conclusion: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. Registration: ClinicalTrials.gov NCT03909919. Graphical Abstract [ABSTRACT FROM AUTHOR]

In this paper, we advocate and expand upon a previously described monitoring strategy for efficient and robust estimation of disease prevalence and case numbers within closed and enumerated populations such as schools, workplaces, or retirement communities. The proposed design relies largely on voluntary testing, which is notoriously biased (e.g. in the case of coronavirus disease 2019) due to nonrepresentative sampling. The approach yields unbiased and comparatively precise estimates with no assumptions about factors underlying selection of individuals for voluntary testing, building on the strength of what can be a small random sampling component. This component enables the use of a recently proposed "anchor stream" estimator, a well-calibrated alternative to classical capture-recapture (CRC) estimators based on 2 data streams. We show that this estimator is equivalent to a direct standardization based on "capture," that is, selection (or not) by the voluntary testing program, made possible by means of a key parameter identified by design. This equivalency simultaneously allows for novel 2-stream CRC-like estimation of general mean values (e.g. means of continuous variables like antibody levels or biomarkers). For inference, we propose adaptations of Bayesian credible intervals when estimating case counts and bootstrapping when estimating means of continuous variables. We use simulations to demonstrate significant precision benefits relative to random sampling alone. [ABSTRACT FROM AUTHOR]

The problem of how to best select variables for confounding adjustment forms one of the key challenges in the evaluation of exposure effects in observational studies, and has been the subject of vigorous recent activity in causal inference. A major drawback of routine procedures is that there is no finite sample size at which they are guaranteed to deliver exposure effect estimators and associated confidence intervals with adequate performance. In this work, we will consider this problem when inferring conditional causal hazard ratios from observational studies under the assumption of no unmeasured confounding. The major complication that we face with survival data is that the key confounding variables may not be those that explain the censoring mechanism. In this paper, we overcome this problem using a novel and simple procedure that can be implemented using off‐the‐shelf software for penalized Cox regression. In particular, we will propose tests of the null hypothesis that the exposure has no effect on the considered survival endpoint, which are uniformly valid under standard sparsity conditions. Simulation results show that the proposed methods yield valid inferences even when covariates are high‐dimensional. [ABSTRACT FROM AUTHOR]

Post‐market active safety monitoring is important for the timely capture of safety signals associated with exposure to a new vaccine or drug. The group sequential analysis is a common method employed in safety surveillance. Specifically, it compares the post‐vaccination incidence of adverse event (AE) in a vaccinated population with a pre‐specified reference level by sequentially conducting hypothesis testing during the surveillance. When the number of AEs is "too high", a safety signal is identified. If the null hypothesis is never rejected, the vaccine is considered safe. Such an approach does not account for either the variation in determining the reference risk from a control population or the seasonality effect. Furthermore, not rejecting the null could be due to a lack of power and cannot always be interpreted as proof of safety. In this paper, we proposed a new group sequential test procedure fully accounting for both seasonality and variation from the historical controls. More importantly, we proposed to construct a confidence interval for the relative AE risk between the exposed and control groups at the end of the study, which can be used to quantify the safety of the vaccine. The proposed method is illustrated via real‐data examples on anaphylaxis and examined by extensive simulation studies. [ABSTRACT FROM AUTHOR]

Introduction Neuromuscular electrical stimulation (NMES) is a treatment to prevent or reverse acquired disability in hospitalised adults. We conducted a systematic review and meta-analysis of its effectiveness. Method We searched MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health (CINAHL) and the Cochrane library. Inclusion criteria: randomised controlled trials of hospitalised adult patients comparing NMES to control or usual care. The primary outcome was muscle strength. Secondary outcomes were muscle size, function, hospital length of stay, molecular and cellular biomarkers, and adverse effects. We assessed risk of bias using the Cochrane risk-of-bias tool. We used Review Manager (RevMan) software for data extraction, critical appraisal and synthesis. We assessed certainty using the Grading of Recommendations Assessment, Development and Evaluation tool. Results A total of 42 papers were included involving 1,452 participants. Most studies had unclear or high risk of bias. NMES had a small effect on muscle strength (moderate certainty) (standardised mean difference (SMD) = 0.33; P  < 0.00001), a moderate effect on muscle size (moderate certainty) (SMD = 0.66; P  < 0.005), a small effect on walking performance (moderate certainty) (SMD = 0.48; P  < 0.0001) and a small effect on functional mobility (low certainty) (SMD = 0.31; P  < 0.05). There was a small and non-significant effect on health-related quality of life (very low certainty) (SMD = 0.35; P  > 0.05). In total, 9% of participants reported undesirable experiences. The effects of NMES on length of hospital stay, and molecular and cellular biomarkers were unclear. Conclusions NMES is a promising intervention component that might help to reduce or prevent hospital-acquired disability. [ABSTRACT FROM AUTHOR]

Bootstrap is a useful computational tool for statistical inference, but it may lead to erroneous analysis under complex survey sampling. In this paper, we propose a unified bootstrap method for stratified multi‐stage cluster sampling, Poisson sampling, simple random sampling without replacement and probability proportional to size sampling with replacement. In the proposed bootstrap method, we first generate bootstrap finite populations, apply the same sampling design to each bootstrap population to get a bootstrap sample, and then apply studentization. The second‐order accuracy of the proposed bootstrap method is established by the Edgeworth expansion. Simulation studies confirm that the proposed bootstrap method outperforms the commonly used Wald‐type method in terms of coverage, especially when the sample size is not large. [ABSTRACT FROM AUTHOR]

Background: ambulatory blood pressure monitoring (ABPM) may be helpful for the management of hypertension, but little is known about its tolerability in people with dementia. Objective: to review the published evidence to determine the tolerability of ABPM in people with dementia. Methods: English language search conducted in MEDLINE and EMBASE, using Ambulatory blood pressure' AND 'Dementia' (and associated synonyms) from 1996 to March 2015. Inclusion criteria: people diagnosed with dementia AND in whom blood pressure was measured using ABPM. The initial search was undertaken using title and abstract reviews, with selected papers being agreed for inclusion by two reviewers. Potentially eligible papers were assessed, and high-quality papers were retained. Two reviewers agreed the abstracted data for analysis. Meta-analysis was used to combine results across studies. Results: of the 221 screened abstracts, 13 studies (6%) met inclusion criteria, 5 had sufficient data and were of sufficient quality, involving 461 participants, most of whom had mild--moderate dementia. 77.7% (95% CI 62.2-93.2%) were able to tolerate ABPM; agreement with office BP was moderate to weak (two studies only--coefficients 0.3-0.38 for systolic blood pressure and 0.11-0.32 for diastolic blood pressure). One study compared home BP monitoring by a relative or ambulatory BP monitoring with office BP measures and found high agreement (ϗ 0.81). The little available evidence suggested increased levels of dementia being associated with reduced tolerability. Conclusions: ABPM is well tolerated in people with mild-moderate dementia and provides some additional information over and above office BP alone. However, few studies have addressed ABPM in people with more severe dementia. [ABSTRACT FROM AUTHOR]

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard. Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region. Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of -0.85 SDs (95% CI: -0.94, -0.76). Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing regions. [ABSTRACT FROM AUTHOR]

Background the prevalence of adverse drug reactions (ADRs) in hospitalised older patients, their clinical presentations, causative drugs, severity, preventability and measurable outcomes are unclear, ADRs being an increasing challenge to older patient safety. Methods we systematically searched PubMed, Embase, EBSCO-CINAHL, the Cochrane Library, 'rey' literature and relevant systematic review bibliographies, published from database inception to March 2020. We included any study reporting occurrence of in-hospital ADRs as primary or secondary outcomes in hospitalised older adults (mean age ≥ 65 years). Two authors independently extracted relevant information and appraised studies for bias. Study characteristics, ADR clinical presentations, causative drugs, severity, preventability and clinical outcomes were analysed. Study estimates were pooled using random-effects meta-analytic models. Results from 2,399 abstracts, we undertook full-text screening in 286, identifying 27 studies (29 papers). Final analysis yielded a pooled ADR prevalence of 16% (95%CI 12–22%, I 2 98%, τ 2 0.8585), in a population of 20,153 hospitalised patients aged ≥65 years of whom 2,479 patients experienced ≥ one ADR. ADR ascertainment was highly heterogeneous. Almost 48.3% of all ADRs involved five presentations: fluid/electrolyte disturbances (17.3%), gastrointestinal motility/defaecation disorders (13.3%), renal disorders (8.2%), hypotension/blood pressure dysregulation disorders/shock (5.5%) and delirium (4.1%). Four drug classes accounted for 57.8% of causative medications i.e. diuretics (19.8%), anti-bacterials (14.8%), antithrombotic agents (12.2%) and analgesics (10.9%). Pooled analysis of severity was not feasible. Four studies reported the majority of ADRs as preventable (55–95%). Conclusions on average, 16% of hospitalised older patients experience significant ADRs, varying in severity and mostly preventable, with commonly prescribed drug classes accounting for most ADRs. [ABSTRACT FROM AUTHOR]

Aims Psychological factors are among the most suspected indicators which may cause atherosclerosis. Coping strategies modifying psychological stress may be significantly associated with health outcomes. However, little is known about the influence of adaptive and maladaptive coping strategies on major adverse cardiovascular disease (CVD) events. The purpose of this study is to examine this idea among a sample of adults. Design: cohort study. Methods and results The Isfahan cohort study (ICS) is a longitudinal population-based, prospective study. Participants (⁠ N = 6323 individuals aged 35 years or greater at baseline) were selected by multistage random sampling with 6-year intervals (i.e. 2001: 6323 individuals, 2007: 3296 individuals, and 2013: 1706 individuals). Adaptive and maladaptive coping strategies were evaluated by a multicomponent self-administered stress management paper-based questionnaire. All CVD events were confirmed by a blinded panel of experts and a marginal cox regression model was used to model the survival data. Adaptive coping strategies could be protective against CVD events with hazard ratios (95% confidence interval) [0.97 (0.95–0.99)] and maladaptive coping strategies seem to be a risk factor, 1.02 (1.01–1.04) in the whole population. Individuals younger than 60 showed similar results, with 0.96 (0.93–0.98) and 1.04 (1.01–1.07) for adaptive and maladaptive coping strategies, respectively. However, these findings were not replicated among seniors older than age 60. Conclusion Based on our results, coping strategies have an important role in cardiovascular events, particularly among young adults. According to the results, informing patients about adaptive stress management may promote primary prevention of CVD events. [ABSTRACT FROM AUTHOR]

Reinforcement learning is a general technique that allows an agent to learn an optimal policy and interact with an environment in sequential decision‐making problems. The goodness of a policy is measured by its value function starting from some initial state. The focus of this paper was to construct confidence intervals (CIs) for a policy's value in infinite horizon settings where the number of decision points diverges to infinity. We propose to model the action‐value state function (Q‐function) associated with a policy based on series/sieve method to derive its confidence interval. When the target policy depends on the observed data as well, we propose a SequentiAl Value Evaluation (SAVE) method to recursively update the estimated policy and its value estimator. As long as either the number of trajectories or the number of decision points diverges to infinity, we show that the proposed CI achieves nominal coverage even in cases where the optimal policy is not unique. Simulation studies are conducted to back up our theoretical findings. We apply the proposed method to a dataset from mobile health studies and find that reinforcement learning algorithms could help improve patient's health status. A Python implementation of the proposed procedure is available at https://github.com/shengzhang37/SAVE. [ABSTRACT FROM AUTHOR]

Data collected from a validation substudy permit calculation of a bias-adjusted estimate of effect that is expected to equal the estimate that would have been observed had the gold standard measurement been available for the entire study population. In this paper, we develop and apply a framework for adaptive validation to determine when sufficient validation data have been collected to yield a bias-adjusted effect estimate with a prespecified level of precision. Prespecified levels of precision are decided a priori by the investigator, based on the precision of the conventional estimate and allowing for wider confidence intervals that would still be substantively meaningful. We further present an applied example of the use of this method to address exposure misclassification in a study of transmasculine/transfeminine youth and self-harm. Our method provides a novel approach to effective and efficient estimation of classification parameters as validation data accrue, with emphasis on the precision of the bias-adjusted estimate. This method can be applied within the context of any parent epidemiologic study design in which validation data will be collected and modified to meet alternative criteria given specific study or validation study objectives. [ABSTRACT FROM AUTHOR]

Estimators based on Wasserstein distributionally robust optimization are obtained as solutions of min-max problems in which the statistician selects a parameter minimizing the worst-case loss among all probability models within a certain distance from the underlying empirical measure in a Wasserstein sense. While motivated by the need to identify optimal model parameters or decision choices that are robust to model misspecification, these distributionally robust estimators recover a wide range of regularized estimators, including square-root lasso and support vector machines, among others. This paper studies the asymptotic normality of these distributionally robust estimators as well as the properties of an optimal confidence region induced by the Wasserstein distributionally robust optimization formulation. In addition, key properties of min-max distributionally robust optimization problems are also studied; for example, we show that distributionally robust estimators regularize the loss based on its derivative, and we also derive general sufficient conditions which show the equivalence between the min-max distributionally robust optimization problem and the corresponding max-min formulation. [ABSTRACT FROM AUTHOR]

Context Ensuring a healthy pregnancy and achieving optimal gestational weight gain (GWG) are important for maternal and child health. Nevertheless, the nutritional advice provided during pregnancy is often conflicting, suggesting limited adherence to clinical practice guidelines (CPGs). Objective The aim of this review was to identify all CPGs on maternal nutrition and GWG and to critically appraise their methodological quality. Data Sources The MEDLINE/PubMed, Cochrane, Guidelines International Network, and BMJ Best Practice databases, along with gray literature, were searched from inception until February 2019 for CPGs and consensus, position, and practice papers. Study Selection Clinical practice guidelines published in English and containing advice on maternal nutrition or GWG were eligible. Data Extraction Two authors independently extracted data on items pertaining to maternal nutrition or GWG, and CPGs were appraised using the AGREE II instrument. Results Twenty-two CPGs were included. All scored adequately in the "scope" domain, but most were considered inadequate with regard to stakeholder involvement, rigor of development, applicability, and editorial independence. Many CPGs lacked patient or dietician involvement, and more than half did not disclose funding sources or conflicts of interest. Guidance on GWG was based mostly on Institute of Medicine thresholds, while nutrition recommendations appeared scattered and heterogeneous. Conclusion Despite the importance of maternal nutrition and the plethora of advising bodies publishing relevant guidance, there is room for substantial improvement in terms of development standards and content of nutritional recommendations. Systematic review registration PROSPERO registration number CRD42019120898. [ABSTRACT FROM AUTHOR]

This paper develops a novel wild bootstrap procedure to construct robust bias-corrected valid confidence intervals for fuzzy regression discontinuity designs, providing an intuitive complement to existing robust bias-corrected methods. The confidence intervals generated by this procedure are valid under conditions similar to the procedures proposed by Calonico et al. (2014) and related literature. Simulations provide evidence that this new method is at least as accurate as the plug-in analytical corrections when applied to a variety of data-generating processes featuring endogeneity and clustering. Finally, we demonstrate its empirical relevance by revisiting Angrist and Lavy (1999) analysis of class size on student outcomes. [ABSTRACT FROM AUTHOR]

This paper proposes nonparametric kernel-smoothing estimation for panel data to examine the degree of heterogeneity across cross-sectional units. We first estimate the sample mean, autocovariances, and autocorrelations for each unit and then apply kernel smoothing to compute their density functions. The dependence of the kernel estimator on bandwidth makes asymptotic bias of very high order affect the required condition on the relative magnitudes of the cross-sectional sample size (⁠|$N$|⁠) and the time-series length (⁠|$T$|⁠). In particular, it makes the condition on |$N$| and |$T$| stronger and more complicated than those typically observed in the long-panel literature without kernel smoothing. We also consider a split-panel jackknife method to correct bias and construction of confidence intervals. An empirical application illustrates our procedure. [ABSTRACT FROM AUTHOR]