Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Reducing rehospitalization has been a primary focus of hospitals and payors. Recurrence of Clostridioides difficile infection (CDI) is common and often results in rehospitalization. Factors that influence rehospitalization for CDI are not well understood.

To determine the risk factors that influence rehospitalization caused by CDI.

A retrospective cohort study from January 1, 2018, to December 31, 2018, of patients aged ≥18 who tested positive for C. difficile while hospitalized.

Academic hospital.

The risk of rehospitalization was assessed across exposures during and after the index hospitalization using a Cox proportional hazards model. The primary outcome of this study was 60-day CDI-related rehospitalization.

There were 559 hospitalized patients with a positive CD test during the study period, and 408 patients were included for analysis. All-cause rehospitalization was 46.1% within 60 days of the index hospital discharge. Within 60 days of discharge, 68 patients developed CDI, of which 72.5% (49 of 68) were rehospitalized specifically for the management of CDI. The risk of rehospitalization in patients with CDI was higher among patients who were exposed to systemic antibiotics ([adjusted hazard ratio] aHR: 2.78; 95% CI, 1.36–5.64) and lower among patients who had post-discharge follow-up addressing C. difficile (aHR: 0.53; 95% CI, 0.28–0.98).

Exposure to systemic antibiotics increased the risk of rehospitalization due to CDI, while post-discharge follow-up decreased the risk of rehospitalization due to CDI. Comprehensive transitions of care for hospitalized patients with C. difficile may reduce the risk of CDI-related rehospitalization.

This study aimed to analyse the influence of improved antenatal detection on the course, contemporary outcomes, and mortality risk factors of the complete atrioventricular block during fetal-neonatal and childhood periods in South Wales.

The clinical characteristics and outcomes of complete atrioventricular block in patients without structural heart disease at the University Hospital of Wales from January 1966 to April 2021 were studied. Patients were divided into two groups according to their age at diagnosis: I-fetal-neonatal and II-childhood. Contemporary outcomes during the post-2001 era were compared with historical data preceding fetal service development and hence earlier detection.

There were 64 patients: 26 were identified in the fetal-neonatal period and the remaining 38 in the childhood period. Maternal antibodies/systemic lupus erythematosus disease (anti-Ro/Sjögren’s-syndrome-related Antigen A and/or anti-La/Sjögren’s-syndrome-related Antigen B) were present in 15 (57.7%) of the fetal-neonatal. Fetal/neonatal and early diagnosis increased after 2001 with an incidence of 1:25000 pregnancies. Pacemaker implantation was required in 34 patients, of whom 13 were diagnosed in the fetal-neonatal group. Survival rates in cases identified before 2001 were at 96.3% (26/27), whereas it was 83.8% (31/37) in patients diagnosed after 2001 (P > 0.05). Other mortality risk factors comprised a lower gestational week at birth, maternal antibodies, and an average ventricular heart rate of < 55 bpm.

Fetal diagnosis of complete atrioventricular block is still portends high fetal and neonatal mortality and morbidity despite significantly improved antenatal detection after 2001. Pacemaker intervention is needed earlier in the fetal-neonatal group. Whether routine antenatal medical treatment might alter this outcome calls for further prospective multicentre studies.

The cost effectiveness of treating Bell’s palsy with prednisolone in children is unknown. This study aimed to assess the cost effectiveness of prednisolone, compared with placebo, in treating Bell’s Palsy in children from a healthcare sector perspective.

This economic evaluation was a prospectively planned secondary analysis of a triple-blind randomized superiority trial conducted from 2015 to 2020 that compared prednisolone with placebo. The time horizon was six months after randomization. The 180 participants were aged from six months to 17 years and presented within 72 hours of onset of clinician diagnosed Bell’s palsy. Interventions were oral prednisolone (1 mg per kg daily) or taste-matched placebo administered for ten days. Incremental cost-effectiveness ratios comparing prednisolone with placebo were estimated. Costs included medication costs, doctor visits, and medical tests over the six-month study period. Effectiveness was measured using quality-adjusted life-years (QALYs) derived from the Child Health Utility 9D instrument. Nonparametric bootstrapping was performed to capture uncertainties. Prespecified subgroup analyses by age (12 to 17 years versus <12 years) were performed.

The mean cost per patient was USD188 in the prednisolone group and USD121 in the placebo group over the six-month period (difference USD66, 95% confidence interval [CI]: 47, 179). The mean QALYs gained over six months were 0.45 in the prednisolone group and 0.44 in the placebo group (difference 0.01, 95%CI: -0.01, 0.03). Prednisolone was very likely cost effective given a conventional willingness-to-pay threshold of USD 50,000 per QALY gained (the cost per additional QALY gained was USD6,625 using prednisolone compared with placebo). Subgroup analysis suggested that this was primarily driven by the high probability of prednisolone being cost effective in children aged 12 to 17 years (98%), compared with those younger than 12 years (51%).

This study provides new evidence to stakeholders and policy makers who are considering whether to make prednisolone available for treating Bell’s palsy in children aged 12 to 17 years.

Perinatal maternal depression may affect fetal neurodevelopment directly or indirectly via exposures such as smoking, alcohol, or antidepressant use. The relative contribution of these risk factors on child executive function (EF) has not been explored systematically.

A prospective pregnancy cohort of 197 women and their children was studied to determine whether maternal depression diagnosis and the trajectory of maternal depressive symptoms (MDSs) from early pregnancy to 12 months postpartum predicts child EF at age 4 (measured using the preschool age psychiatric assessment, NEPSY-II, and Shape School task) using latent growth curve modeling. Indirect effects of smoking, alcohol, and antidepressant use were also formally tested.

Increasing maternal perinatal depressive symptoms over time predicted more inattentive symptoms, poorer switching, and motor inhibition, but not cognitive inhibition. When adjusted for multiple comparison, and after accounting for maternal cognition and education, the association with child inattentive symptoms remained significant. However, diagnosed depression did not predict child EF outcomes. Prenatal exposure to smoking, alcohol, and antidepressants also did not mediate pathways from depressive symptoms to EF outcomes. Our findings were limited by sample size and statistical power to detect outcome effects of smaller effect size.

This study suggests that increasing MDSs over the perinatal period is associated with poorer EF outcomes in children at age 4 – independent of prenatal smoking, drinking, or antidepressant use. Depressive chronicity, severity, and postpartum influences may play crucial roles in determining childhood outcomes of EF.

Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals.

The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence.

In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative – a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping.

These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis.