Clinical prediction rules (CPRs) that predict the absolute risk of a clinical condition or future outcome for individual patients are abundant in the medical literature; however, systematic reviews have demonstrated shortcomings in the methodological quality and reporting of prediction studies. To maximise the potential and clinical usefulness of CPRs, they must be rigorously developed and validated, and their impact on clinical practice and patient outcomes must be evaluated. This review aims to present a comprehensive overview of the stages involved in the development, validation and evaluation of CPRs, and to describe in detail the methodological standards required at each stage, illustrated with examples where appropriate. Important features of the study design, statistical analysis, modelling strategy, data collection, performance assessment, CPR presentation and reporting are discussed, in addition to other, often overlooked aspects such as the acceptability, cost-effectiveness and longer-term implementation of CPRs, and their comparison with clinical judgement. Although the development and evaluation of a robust, clinically useful CPR is anything but straightforward, adherence to the plethora of methodological standards, recommendations and frameworks at each stage will assist in the development of a rigorous CPR that has the potential to contribute usefully to clinical practice and decision-making and have a positive impact on patient care.

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We revisit the well‐known but often misunderstood issue of (non)collapsibility of effect measures in regression models for binary and time‐to‐event outcomes. We describe an existing simple but largely ignored procedure for marginalizing estimates of conditional odds ratios and propose a similar procedure for marginalizing estimates of conditional hazard ratios (allowing for right censoring), demonstrating its performance in simulation studies and in a reanalysis of data from a small randomized trial in primary biliary cirrhosis patients. In addition, we aim to provide an educational summary of issues surrounding (non)collapsibility from a causal inference perspective and to promote the idea that the words conditional and adjusted (likewise marginal and unadjusted) should not be used interchangeably.

Probabilities of AHT can be estimated on the basis of different combinations of clinical features. The model could be further developed in a prospective large-scale study, with an expanded clinical data set, to contribute to a more refined tool to inform clinical decisions about the likelihood of AHT.

Aim: A systematic review of the scientific literature to define clinical indicators distinguishing inflicted (iBI) from non-inflicted brain injury (niBI). Methods: An all language literature search of 20 electronic databases, websites, references and bibliographies from 1970-2008 was carried out. Relevant studies were independently reviewed by two trained reviewers, with a third review where required. Inclusion criteria included primary comparative studies of iBI and niBI in children aged ,18 years, with high surety of diagnosis describing key clinical features. Multilevel logistic regression analysis was conducted, determining the positive predictive value (PPV) and odds ratios (OR) with p values for retinal haemorrhage, rib/long bone/skull fractures, apnoea, seizures and bruising to head/neck. Results: 8151 studies were identified, 320 were reviewed and 14 included, representing 1655 children, 779 with iBI. Gender was not a discriminatory feature. In a child with intracranial injury, apnoea (PPV 93%, OR 17.06, p,0.001) and retinal haemorrhage (PPV 71%, OR 3.504, p = 0.03) were the features most predictive of iBI. Rib fractures (PPV 73%, OR 3.03, p = 0.13) had a similar PPV to retinal haemorrhages, but there were less data for analysis. Seizures and long bone fractures were not discriminatory, and skull fracture and head/neck bruising were more associated with niBI, although not significantly so.Conclusions: This systematic review shows that apnoea and retinal haemorrhage have a high odds ratio for association with iBI. This review identifies key features that should be recorded in the assessment of children where iBI is suspected and may help clinicians to define the likelihood of iBI.

Summary. The problem of analysing longitudinal data that are complicated by possibly informative drop-out has received considerable attention in the statistical literature. Most researchers have concentrated on either methodology or application, but we begin this paper by arguing that more attention could be given to study objectives and to the relevant targets for inference. Next we summarize a variety of approaches that have been suggested for dealing with drop-out. A long-standing concern in this subject area is that all methods require untestable assumptions. We discuss circumstances in which we are willing to make such assumptions and we propose a new and computationally efficient modelling and analysis procedure for these situations. We assume a dynamic linear model for the expected increments of a constructed variable, under which subject-specific random effects follow a martingale process in the absence of drop-out. Informal diagnostic procedures to assess the tenability of the assumption are proposed. The paper is completed by simulations and a comparison of our method and several alternatives in the analysis of data from a trial into the treatment of schizophrenia, in which approximately 50% of recruited subjects dropped out before the final scheduled measurement time.

ObjectivesThe influence of neighbourhood deprivation on the risk of harmful alcohol consumption, measured by the separate categories of excess consumption and binge drinking, has not been studied. The study objective was to investigate the effect of neighbourhood deprivation with age, gender and socioeconomic status (SES) on (1) excess alcohol consumption and (2) binge drinking, in a representative population survey.DesignCross-sectional study: multilevel analysis.SettingWales, UK, adult population ∼2.2 million.Participants58 282 respondents aged 18 years and over to four successive annual Welsh Health Surveys (2003/2004–2007), nested within 32 692 households, 1839 census lower super output areas and the 22 unitary authority areas in Wales.Primary outcome measureMaximal daily alcohol consumption during the past week was categorised using the UK Department of Health definition of ‘none/never drinks’, ‘within guidelines’, ‘excess consumption but less than binge’ and ‘binge’. The data were analysed using continuation ratio ordinal multilevel models with multiple imputation for missing covariates.ResultsRespondents in the most deprived neighbourhoods were more likely to binge drink than in the least deprived (adjusted estimates: 17.5% vs 10.6%; difference=6.9%, 95% CI 6.0 to 7.8), but were less likely to report excess consumption (17.6% vs 21.3%; difference=3.7%, 95% CI 2.6 to 4.8). The effect of deprivation varied significantly with age and gender, but not with SES. Younger men in deprived neighbourhoods were most likely to binge drink. Men aged 35–64 showed the steepest increase in binge drinking in deprived neighbourhoods, but men aged 18–24 showed a smaller increase with deprivation.ConclusionsThis large-scale population study is the first to show that neighbourhood deprivation acts differentially on the risk of binge drinking between men and women at different age groups. Understanding the socioeconomic patterns of harmful alcohol consumption is important for public health policy development.

Blood coagulation functions as part of the innate immune system by preventing bacterial invasion and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for normal hemostasis and promoted coagulation factor activities in a Ca 2+ -and phosphatidylserine (PS)-dependent manner. In wild-type mice, hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) † Corresponding author. o-donnellvb@cardiff.ac.uk (V.B.O'D.); collinspw@cardiff.ac.uk (P.W.C.). * These authors contributed jointly to the work. Author contributions:Experiments were conducted by SNL, DAS, GM, RU, AOC, DF, JM, SR, VJT, AB, SF, MA, MH, KAR, CPT, JA and GK, and designed by SNL, DAS, PDG, SH, VBO, SAJ, PRT, PWC, PVJ. CLP and SO provided clinical samples. AP provided supervision and training. SNL, DAS, VBO and PWC wrote the paper. All authors edited the manuscript. Competing interests:The authors have declared that they have no competing interests. Europe PMC Funders GroupAuthor Manuscript Sci Signal. Author manuscript; available in PMC 2017 December 07. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts enhanced coagulation and restored normal hemostasis in clotting-deficient animals genetically lacking p12-LOX or 12/15-LOX activity. Murine platelets generated 22 eoxPL species, all of which were missing in the absence of p12-LOX. Humans with the thrombotic disorder antiphospholipid syndrome (APS) had statistically significantly increased HETE-PLs in platelets and leukocytes, as well as greater HETE-PL immunoreactivity, than healthy controls. HETE-PLs enhanced membrane binding of the serum protein β2GPI (β2-glycoprotein I), an event considered central to the autoimmune reactivity responsible for APS symptoms. Correlation network analysis of 47 platelet eoxPL species in platelets from APS and control subjects identified their enzymatic origin and revealed a complex network of regulation, with the abundance of 31 p12-LOX-derived eoxPL molecules substantially increased in APS. In summary, circulating blood cells generate networks of eoxPL molecules, including HETE-PLs, which change membrane properties to enhance blood coagulation and contribute to the excessive clotting and immunoreactivity of patients with APS.