The 50 most-cited articles in BMJ, 2024

The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum reporting recommendations for studies developing or evaluating the performance of a prediction model. Methodological advances in the field of prediction have since included the widespread use of artificial intelligence (AI) powered by machine learning methods to develop prediction models. An update to the TRIPOD statement is thus needed. TRIPOD+AI provides harmonised guidance for reporting prediction model studies, irrespective of whether regression modelling or machine learning methods have been used. The new checklist supersedes the TRIPOD 2015 checklist, which should no longer be used. This article describes the development of TRIPOD+AI and presents the expanded 27 item checklist with more detailed explanation of each reporting recommendation, and the TRIPOD+AI for Abstracts checklist. TRIPOD+AI aims to promote the complete, accurate, and transparent reporting of studies that develop a prediction model or evaluate its…

OBJECTIVE: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN: Systematic umbrella review of existing meta-analyses. DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response…

Evaluating the performance of a clinical prediction model is crucial to establish its predictive accuracy in the populations and settings intended for use. In this article, the first in a three part series, Collins and colleagues describe the importance of a meaningful evaluation using internal, internal-external, and external validation, as well as exploring heterogeneity, fairness, and generalisability in model performance.

OBJECTIVE: To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. DESIGN: Systematic review and network meta-analysis. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool. DATA SOURCES: Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression. RESULTS: 218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga…

Abstract Objective To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. Design Systematic review and network meta-analysis. Data sources PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. Eligibility criteria for selecting studies Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. Results 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A 1c and…

Predicting future outcomes of patients is essential to clinical practice, with many prediction models published each year. Empirical evidence suggests that published studies often have severe methodological limitations, which undermine their usefulness. This article presents a step-by-step guide to help researchers develop and evaluate a clinical prediction model. The guide covers best practices in defining the aim and users, selecting data sources, addressing missing data, exploring alternative modelling options, and assessing model performance. The steps are illustrated using an example from relapsing-remitting multiple sclerosis. Comprehensive R code is also provided.

Bladder cancer remains a leading cause of cancer death worldwide and is associated with substantial impacts on patient quality of life, morbidity, mortality, and cost to the healthcare system. Gross hematuria frequently precedes the diagnosis of bladder cancer. Non-muscle-invasive bladder cancer (NMIBC) is managed initially with transurethral resection of a bladder tumor (TURBT), followed by a risk stratified approach to adjuvant intravesical therapy (IVe), and is associated with an overall survival of 90%. However, cure rates remain lower for muscle invasive bladder cancer (MIBC) owing to a variety of factors. NMIBC and MIBC groupings are heterogeneous and have unique pathological and molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers and luminal and basal molecular subtypes of MIBC with distinct treatment responses. For NMIBC, IVe immunotherapy (primarily BCG) is the gold standard treatment for high grade and high risk NMIBC to reduce or prevent both recurrence and progression after initial TURBT; novel trials incorporate immune…

External validation studies are an important but often neglected part of prediction model research. In this article, the second in a series on model evaluation, Riley and colleagues explain what an external validation study entails and describe the key steps involved, from establishing a high quality dataset to evaluating a model’s predictive performance and clinical usefulness.

Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness that typically affects symmetrically distributed small and large joints. Without effective treatment, significant joint damage, disability, and work loss develop, owing to chronic inflammation of the joint lining (synovium). Over the past 25 years, the management of this condition has been revolutionized, resulting in substantially higher levels of disease remission and better long term outcomes. This improvement reflects a paradigm shift towards early and aggressive pharmacological intervention coupled with a proliferation in treatment choice, in turn related to enhanced pathobiological understanding and the advent of new drugs for rheumatoid arthritis. Following an overview of these developments from a historical perspective, and with a general audience in mind, this review focuses on newer, targeted treatments in an ever evolving landscape. The review highlights ongoing areas of debate and unmet need, including the…

Abstract Objective To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. Design Randomised, double blind, placebo controlled, phase 3 study. Setting 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. Participants 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. Interventions Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator’s choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases,…

OBJECTIVES: To determine the extent and content of academic publishers' and scientific journals' guidance for authors on the use of generative artificial intelligence (GAI). DESIGN: Cross sectional, bibliometric study. SETTING: Websites of academic publishers and scientific journals, screened on 19-20 May 2023, with the search updated on 8-9 October 2023. PARTICIPANTS: Top 100 largest academic publishers and top 100 highly ranked scientific journals, regardless of subject, language, or country of origin. Publishers were identified by the total number of journals in their portfolio, and journals were identified through the Scimago journal rank using the Hirsch index (H index) as an indicator of journal productivity and impact. MAIN OUTCOME MEASURES: The primary outcomes were the content of GAI guidelines listed on the websites of the top 100 academic publishers and scientific journals, and the consistency of guidance between the publishers and their affiliated journals. RESULTS: Among the top 100 largest publishers, 24% provided guidance on the use of GAI, of which 15 (63%) were…

This article provides updated guidance on methods for conducting rapid reviews of effectiveness, targeted at Cochrane and other stakeholders interested in the methodology of rapid reviews. The guidance, developed by the Cochrane Rapid Reviews Methods Group, builds upon previous interim guidance, and incorporates changes based on an evaluation of its application, a scope of the literature on rapid review methodology, and input from a diverse group of experts in rapid review methods. The guidance consists of 24 specific recommendations supporting the conduct of rapid reviews, applicable both within and outside Cochrane. It underscores the importance of considering the appropriateness of undertaking rapid reviews and advocates for a tailored, iterative approach to each review. Key defining features of rapid reviews, such as restricted methods, how the dimension of timelines factors into rapid reviews, and the involvement of knowledge users (eg, patient and public partners, healthcare providers, policy makers), are outlined. The paper presents a definition of a Cochrane rapid review and…

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and…

An external validation study evaluates the performance of a prediction model in new data, but many of these studies are too small to provide reliable answers. In the third article of their series on model evaluation, Riley and colleagues describe how to calculate the sample size required for external validation studies, and propose to avoid rules of thumb by tailoring calculations to the model and setting at hand.

Estimands can be used in studies of healthcare interventions to clarify the interpretation of treatment effects. The addendum to the ICH E9 harmonised guideline on statistical principles for clinical trials (ICH E9(R1)) describes a framework for using estimands as part of a study. This paper provides an overview of the estimands framework, as outlined in the addendum, with the aim of explaining why estimands are beneficial; clarifying the terminology being used; and providing practical guidance on using estimands to decide the appropriate study design, data collection, and estimation methods. This article illustrates how to use the estimands framework by applying it to an ongoing trial in emergency bowel surgery. Estimands can be a useful way of clarifying the exact research question being evaluated in a study, both to avoid misinterpretation and to ensure that study methods are aligned to the overall study objectives.

Abstract Objectives To estimate the burden, trends, and inequalities of type 1 diabetes mellitus (T1DM) among older adults at global, regional, and national level from 1990 to 2019. Design Population based study. Population Adults aged ≥65 years from 21 regions and 204 countries and territories (Global Burden of Disease and Risk Factors Study 2019) from 1990 to 2019. Main outcome measures Primary outcomes were T1DM related age standardised prevalence, mortality, disability adjusted life years (DALYs), and average annual percentage change. Results The global age standardised prevalence of T1DM among adults aged ≥65 years increased from 400 (95% uncertainty interval (UI) 332 to 476) per 100 000 population in 1990 to 514 (417 to 624) per 100 000 population in 2019, with an average annual trend of 0.86% (95% confidence interval (CI) 0.79% to 0.93%); while mortality decreased from 4.74 (95% UI 3.44 to 5.9) per 100 000 population to 3.54 (2.91 to 4.59) per 100 000 population, with an average annual trend of −1.00% (95% CI −1.09% to −0.91%), and age standardised DALYs decreased from 113…

OBJECTIVE: To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). DESIGN: Nationwide population based study. SETTING: Longitudinal cohort study in Korea. PARTICIPANTS: 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. MAIN OUTCOME MEASURES: The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. RESULTS: Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in…

The understanding of acute respiratory distress syndrome (ARDS) has evolved greatly since it was first described in a 1967 case series, with several subsequent updates to the definition of the syndrome. Basic science advances and clinical trials have provided insight into the mechanisms of lung injury in ARDS and led to reduced mortality through comprehensive critical care interventions. This review summarizes the current understanding of the epidemiology, pathophysiology, and management of ARDS. Key highlights include a recommended new global definition of ARDS and updated guidelines for managing ARDS on a backbone of established interventions such as low tidal volume ventilation, prone positioning, and a conservative fluid strategy. Future priorities for investigation of ARDS are also highlighted.

Abstract Objective To determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious renal events compared with either drug class alone among patients with type 2 diabetes, and to assess the effect of the combination on the individual components of major adverse cardiovascular events, heart failure, and all cause mortality. Design Population based cohort study using a prevalent new-user design, emulating a trial. Setting UK Clinical Practice Research Datalink linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. Participants Two prevalent new-user cohorts were assembled between January 2013 and December 2020, with follow-up until the end of March 2021. The first cohort included 6696 patients who started GLP-1 receptor agonists and added on SGLT-2 inhibitors, and the second included 8942 patients who started SGLT-2 inhibitors and added on GLP-1 receptor agonists.…

Evidence syntheses adhering to systematic literature searching techniques are a cornerstone of evidence based healthcare. Beyond term based searching in electronic databases, citation searching is a prevalent search technique to identify relevant sources of evidence. However, for decades, citation searching methodology and terminology has not been standardised. An evidence guided, four round Delphi consensus study was conducted with 27 international methodological experts in order to develop the Terminology, Application, and Reporting of Citation Searching (TARCiS) statement. TARCiS comprises 10 specific recommendations, each with a rationale and explanation on when and how to conduct and report citation searching in the context of systematic literature searches. The statement also presents four research priorities, and it is hoped that systematic review teams are encouraged to incorporate TARCiS into standardised workflows.

OBJECTIVE: To compare the effectiveness of interventions for the management of long covid (post-covid condition). DESIGN: Living systematic review. DATA SOURCES: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023. ELIGIBILITY CRITERIA: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care. RESULTS: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range…

OBJECTIVES: To evaluate the effectiveness of safeguards to prevent large language models (LLMs) from being misused to generate health disinformation, and to evaluate the transparency of artificial intelligence (AI) developers regarding their risk mitigation processes against observed vulnerabilities. DESIGN: Repeated cross sectional analysis. SETTING: Publicly accessible LLMs. METHODS: In a repeated cross sectional analysis, four LLMs (via chatbots/assistant interfaces) were evaluated: OpenAI's GPT-4 (via ChatGPT and Microsoft's Copilot), Google's PaLM 2 and newly released Gemini Pro (via Bard), Anthropic's Claude 2 (via Poe), and Meta's Llama 2 (via HuggingChat). In September 2023, these LLMs were prompted to generate health disinformation on two topics: sunscreen as a cause of skin cancer and the alkaline diet as a cancer cure. Jailbreaking techniques (ie, attempts to bypass safeguards) were evaluated if required. For LLMs with observed safeguarding vulnerabilities, the processes for reporting outputs of concern were audited. 12 weeks after initial investigations, the…

OBJECTIVE: To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. DESIGN: Scandinavian cohort study. SETTING: Denmark, Norway, and Sweden, 2007-21. PARTICIPANTS: Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. MAIN OUTCOME MEASURES: Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. RESULTS: The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per…

OBJECTIVES: To examine how the lifetime risks of atrial fibrillation and of complications after atrial fibrillation changed over time. DESIGN: Danish, nationwide, population based cohort study. SETTING: Population of Denmark from 1 January 2000 to 31 December 2022. PARTICIPANTS: 3.5 million individuals (51.7% women and 48.3% men) who did not have atrial fibrillation at 45 years of age or older were followed up until incident atrial fibrillation, migration, death, or end of follow-up, whichever came first. All 362 721 individuals with incident atrial fibrillation (46.4% women and 53.6% men), but with no prevalent complication, were further followed up until incident heart failure, stroke, or myocardial infarction. MAIN OUTCOME MEASURES: 2011-22). RESULTS: The lifetime risk of atrial fibrillation increased from 24.2% in 2000-10 to 30.9% in 2011-22 (difference 6.7% (95% confidence interval 6.5% to 6.8%)). After atrial fibrillation, the most frequent complication was heart failure with a lifetime risk of 42.9% in 2000-10 and 42.1% in 2011-22 (-0.8% (-3.8% to 2.2%)). Individuals with…

Abstract Objective To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19. Design Population based study. Setting UK. Participants 1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019. Main outcome measures The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and…

OBJECTIVE: To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. DESIGN: Population based matched cohort study. SETTING: Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. POPULATION: Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. MAIN OUTCOME MEASURES: The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. RESULTS: Compared with non-use, any antipsychotic use was associated with…

### Key messages Vaccine misinformation on social media has strong effects on behaviour, and the evidence base for interventions to reduce these effects is limited, but better approaches to evidence generation are possible, say Kai Ruggeri and colleagues Effective population level vaccination campaigns are fundamental to public health.123 Counter campaigns, which are as old as the first vaccines,4 disrupt uptake and can threaten public health globally.4 In 2019, public health researchers linked increases in measles cases with the proliferation of global anti-vaccine campaigns.5 Some of these campaigns originated offline but were later amplified and expedited through social media, resulting in real world harms.6 Though crises and genuine safety concerns can also lower vaccine uptake,78 the return of measles after aggressive anti-vaccine campaigns prompted the World Health Organisation to list vaccine hesitancy among the greatest threats to global health (box 1).14 Box 1 ### Vaccine hesitancy Here, we use the term “vaccine hesitancy” as originally defined by WHO9: a “delay in…

Abstract Objectives To replicate previous analyses on the effectiveness of the English human papillomavirus (HPV) vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) using 12 additional months of follow-up, and to investigate effectiveness across levels of socioeconomic deprivation. Design Observational study. Setting England, UK. Participants Women aged 20-64 years resident in England between January 2006 and June 2020 including 29 968 with a diagnosis of cervical cancer and 335 228 with a diagnosis of CIN3. In England, HPV vaccination was introduced nationally in 2008 and was offered routinely to girls aged 12-13 years, with catch-up campaigns during 2008-10 targeting older teenagers aged <19 years. Main outcome measures Incidence of invasive cervical cancer and CIN3. Results In England, 29 968 women aged 20-64 years received a diagnosis of cervical cancer and 335 228 a diagnosis of CIN3 between 1 January 2006 and 30 June 2020. In the birth cohort of women offered vaccination routinely at age 12-13 years, adjusted age…

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the…

Polypharmacy is common in older adults and is associated with adverse drug events, cognitive and functional impairment, increased healthcare costs, and increased risk of frailty, falls, hospitalizations, and mortality. Many barriers exist to deprescribing, but increased efforts have been made to develop and implement deprescribing interventions that overcome them. This narrative review describes intervention components and summarizes findings from published randomized controlled trials that have tested deprescribing interventions in older adults with polypharmacy, as well as reports on ongoing trials, guidelines, and resources that can be used to facilitate deprescribing. Most interventions were medication reviews in primary care settings, and many contained components such as shared decision making and/or a focus on patient care priorities, training for healthcare professionals, patient facing education materials, and involvement of family members, representing great heterogeneity in interventions addressing polypharmacy in older adults. Just over half of study interventions were…

OBJECTIVE: To determine the effect of opioid and stimulant Risk Mitigation Guidance (RMG) dispensations on mortality and acute care visits during the dual public health emergencies of overdose and covid-19. DESIGN: Population based retrospective cohort study. SETTING: British Columbia, Canada. PARTICIPANTS: 5882 people with opioid or stimulant use disorder who received RMG prescriptions for opioids (n=5356) and/or stimulants (n=1061) (535 received both) from 27 March 2020 to 31 August 2021. MAIN OUTCOME MEASURES: All cause and overdose specific mortality and acute care visits in the week after RMG opioid or stimulant dispensation. RMG recipients were matched 1:1 with controls through use of high dimensional propensity score matching. Marginal structural models, executed on weekly time steps, were used to measure the effect of dispensations on outcomes. RESULTS: RMG opioid dispensations of one day or more were associated with reduced all cause mortality (adjusted hazard ratio 0.39, 95% confidence interval 0.25 to 0.60) and overdose related mortality (0.45, 0.27 to 0.75) in the…

OBJECTIVE: To examine the association of ultra-processed food consumption with all cause mortality and cause specific mortality. DESIGN: Population based cohort study. SETTING: Female registered nurses from 11 US states in the Nurses' Health Study (1984-2018) and male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018). PARTICIPANTS: 74 563 women and 39 501 men with no history of cancer, cardiovascular diseases, or diabetes at baseline. MAIN OUTCOME MEASURES: Multivariable Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for the association of ultra-processed food intake measured by semiquantitative food frequency questionnaire every four years with all cause mortality and cause specific mortality due to cancer, cardiovascular, and other causes (including respiratory and neurodegenerative causes). RESULTS: 30 188 deaths of women and 18 005 deaths of men were documented during a median of 34 and 31 years of follow-up, respectively. Compared with those in the lowest quarter of ultra-processed…

OBJECTIVE: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term). DESIGN: Nationwide cohort study. SETTING: Sweden. PARTICIPANTS: weeks between 1998 and 2012. MAIN OUTCOME MEASURES: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment. RESULTS: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had…

OBJECTIVE: To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts. DATA SYNTHESIS AND STUDY QUALITY: Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with…

OBJECTIVE: To examine and interpret trends in UK cancer incidence and mortality for all cancers combined and for the most common cancer sites in adults aged 35-69 years. DESIGN: Retrospective secondary data analysis. DATA SOURCES: Cancer registration data, cancer mortality and national population data from the Office for National Statistics, Public Health Wales, Public Health Scotland, Northern Ireland Cancer Registry, NHS England, and the General Register Office for Northern Ireland. SETTING: 23 cancer sites were included in the analysis in the UK. PARTICIPANTS: Men and women aged 35-69 years diagnosed with or who died from cancer between 1993 to 2018. MAIN OUTCOME MEASURES: Change in cancer incidence and mortality age standardised rates over time. RESULTS: The number of cancer cases in this age range rose by 57% for men (from 55 014 cases registered in 1993 to 86 297 in 2018) and by 48% for women (60 187 to 88 970) with age standardised rates showing average annual increases of 0.8% in both sexes. The increase in incidence was predominantly driven by increases in prostate (male)…

OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid). DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial. SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub. PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287). INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. MAIN…

Global temperatures will continue to rise due to climate change, with high temperature periods expected to increase in intensity, frequency, and duration. Infectious diseases, including vector-borne diseases such as dengue fever and malaria, waterborne diseases such as cholera, and foodborne diseases such as salmonellosis are influenced by temperature and other climatic variables, thus contributing to higher disease burden and associated healthcare costs, particularly in socioeconomically disadvantaged regions. Targeted efforts and investments are therefore needed to support low and middle income countries to prepare for and respond to the increasing infectious disease threats posed by rising temperatures. This can be facilitated by the development and refinement of robust disease and entomological surveillance and early warning systems with integration of climatic information that promote enhanced understanding of the geographic distribution of disease risk. To enhance healthcare workforce capacity and capability to respond to these public health threats, medical curricula and…

Type 1 diabetes is an autoimmune condition resulting in insulin deficiency and eventual loss of pancreatic β cell function requiring lifelong insulin therapy. Since the discovery of insulin more than 100 years ago, vast advances in treatments have improved care for many people with type 1 diabetes. Ongoing research on the genetics and immunology of type 1 diabetes and on interventions to modify disease course and preserve β cell function have expanded our broad understanding of this condition. Biomarkers of type 1 diabetes are detectable months to years before development of overt disease, and three stages of diabetes are now recognized. The advent of continuous glucose monitoring and the newer automated insulin delivery systems have changed the landscape of type 1 diabetes management and are associated with improved glycated hemoglobin and decreased hypoglycemia. Adjunctive therapies such as sodium glucose cotransporter-1 inhibitors and glucagon-like peptide 1 receptor agonists may find use in management in the future. Despite these rapid advances in the field, people living in…

OBJECTIVE: To review the international literature and assess the ways healthcare systems are mitigating and can mitigate their carbon footprint, which is currently estimated to be more than 4.4% of global emissions. DESIGN: Systematic review of empirical studies and grey literature to examine how healthcare services and institutions are limiting their greenhouse gas (GHG) emissions. DATA SOURCES: Eight databases and authoritative reports were searched from inception dates to November 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Teams of investigators screened relevant publications against the inclusion criteria (eg, in English; discussed impact of healthcare systems on climate change), applying four quality appraisal tools, and results are reported in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses). RESULTS: Of 33 737 publications identified, 32 998 (97.8%) were excluded after title and abstract screening; 536 (72.5%) of the remaining publications were excluded after full text review. Two additional papers were identified, screened,…

OBJECTIVE: To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives. DESIGN: Population based study. SETTING: 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer's Global Cancer Observatory, and mortality data from the World Health Organization. POPULATION: Men aged 35-84 years from 26 eligible countries. RESULTS: Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in…

ABSTRACT Objective To assess the risk of intracranial meningioma associated with the use of selected progestogens. Design National case-control study. Setting French National Health Data System (ie, Système National des Données de Santé ). Participants Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls). Main outcome measures Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma…

Abstract Objective To estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes. Design Population based cohort study. Setting Contiguous US. Participants 59 761 494 Medicare fee-for-service beneficiaries aged ≥65 years during 2000-16. Calibrated PM2.5predictions were linked to each participant’s residential zip code as proxy exposure measurements. Main outcome measures Risk of the first hospital admission during follow-up for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, thoracic and abdominal aortic aneurysms, or a composite of these CVD subtypes. A causal framework robust against confounding bias and bias arising from errors in exposure measurements was developed for exposure-response estimations. Results Three year average PM2.5exposure was associated with increased relative risks of first hospital admissions for ischemic heart disease, cerebrovascular disease, heart failure,…

OBJECTIVES: To determine the effect of labour epidural on severe maternal morbidity (SMM) and to explore whether this effect might be greater in women with a medical indication for epidural analgesia during labour, or with preterm labour. DESIGN: Population based study. SETTING: All NHS hospitals in Scotland. PARTICIPANTS: 567 216 women in labour at 24+0 to 42+6 weeks' gestation between 1 January 2007 and 31 December 2019, delivering vaginally or through unplanned caesarean section. MAIN OUTCOME MEASURES: The primary outcome was SMM, defined as the presence of ≥1 of 21 conditions used by the US Centers for Disease Control and Prevention (CDC) as criteria for SMM, or a critical care admission, with either occurring at any point from date of delivery to 42 days post partum (described as SMM). Secondary outcomes included a composite of ≥1 of the 21 CDC conditions and critical care admission (SMM plus critical care admission), and respiratory morbidity. RESULTS: Of the 567 216 women, 125 024 (22.0%) had epidural analgesia during labour. SMM occurred in 2412 women (4.3 per 1000 births,…

Publications of living systematic reviews (LSRs) are increasing rapidly. Guidance facilitating transparent, complete, and accurate reporting of LSRs is needed. This paper reports the development of an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for LSRs (PRISMA-LSR). The PRISMA-LSR extension includes the PRISMA-LSR checklist, the PRISMA-LSR flow diagram, reporting recommendations for the LSR status, and an explanation and elaboration document. This extension has been developed as an “add-on” to the PRISMA 2020 statement, meaning it should be used in addition to the PRISMA 2020 statement. The PRISMA-LSR extension is expected to benefit authors, editors, peer reviewers, and users of LSRs through transparent, complete, and accurate reporting of LSRs.

OBJECTIVE: To quantify time dependent probabilities of outcomes in patients after in-hospital cardiac arrest as a function of duration of cardiopulmonary resuscitation, defined as the interval between start of chest compression and the first return of spontaneous circulation or termination of resuscitation. DESIGN: Retrospective cohort study. SETTING: Multicenter prospective in-hospital cardiac arrest registry in the United States. PARTICIPANTS: 348 996 adult patients (≥18 years) with an index in-hospital cardiac arrest who received cardiopulmonary resuscitation from 2000 through 2021. MAIN OUTCOME MEASURES: Survival to hospital discharge and favorable functional outcome at hospital discharge, defined as a cerebral performance category score of 1 (good cerebral performance) or 2 (moderate cerebral disability). Time dependent probabilities of subsequently surviving to hospital discharge or having favorable functional outcome if patients pending the first return of spontaneous circulation at each minute received further cardiopulmonary resuscitation beyond the time point were…

OBJECTIVE: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of…

Abstract Objective To determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters. Design Nationwide, register based study. Setting Swedish national registers, 1 January 2001 to 31 December 2018. Participants 86 551 women with a first ever diagnosis of perinatal depression ascertained through specialised care and use of antidepressants, and 865 510 women who did not have perinatal depression were identified and matched based on age and calendar year at delivery. To address familial confounding factors, comparisons were made between 270 586 full sisters (women with perinatal depression (n=24 473) and full sisters who did not have this disorder (n=246 113)), who gave at least one singleton birth during the study period. Main outcome measures Primary outcome was death due to any cause. Secondary outcome was cause specific deaths (ie, unnatural and natural causes). Multivariable Cox regression was used to estimate hazard ratios of mortality comparing women with perinatal…

OBJECTIVE: To compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in adults aged 40-69 years with type 2 diabetes. DESIGN: Population based cohort study. SETTING: Korean National Health Insurance Service data, 2013-21. PARTICIPANTS: 110 885 propensity score matched pairs of adults with type 2 diabetes aged 40-69 years who were initiators of either an SGLT-2 inhibitor or a DPP-4 inhibitor. MAIN OUTCOME MEASURES: The primary outcome was new onset dementia. Secondary outcomes were dementia requiring drug treatment and individual types of dementia, including Alzheimer's disease and vascular dementia. Control outcomes were genital infections (positive), and osteoarthritis related clinical encounters and cataract surgery (negative). Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox models. Follow-up time stratified analyses (>2 years and ≤2 years) and subgroup analyses by age, sex, concomitant use of metformin, and baseline cardiovascular risk were performed. RESULTS: 110…