The 100 most-cited articles in BMJ, 2022

OBJECTIVE: To investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Web of Science, PubMed, Medline, and Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 November 2021. REVIEW METHODS: Cohort studies and control arms of trials reporting complications of pregnancy in women with gestational diabetes mellitus were eligible for inclusion. Based on the use of insulin, studies were divided into three subgroups: no insulin use (patients never used insulin during the course of the disease), insulin use (different proportions of patients were treated with insulin), and insulin use not reported. Subgroup analyses were performed based on the status of the country (developed or developing), quality of the study, diagnostic criteria, and screening method. Meta-regression models were applied based on the proportion of patients who had received insulin. RESULTS: 156 studies with 7 506 061 pregnancies were included, and…

OBJECTIVE: To report the global, regional, and national burden of chronic obstructive pulmonary disease (COPD) and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Disease Study 2019. MAIN OUTCOME MEASURES: Data on the prevalence, deaths, and disability adjusted life years (DALYs) of COPD, and its attributable risk factors, were retrieved from the Global Burden of Disease 2019 project for 204 countries and territories, between 1990 and 2019. The counts and rates per 100 000 population, along with 95% uncertainty intervals, were presented for each estimate. RESULTS: In 2019, 212.3 million prevalent cases of COPD were reported globally, with COPD accounting for 3.3 million deaths and 74.4 million DALYs. The global age standardised point prevalence, death, and DALY rates for COPD were 2638.2 (95% uncertainty intervals 2492.2 to 2796.1), 42.5 (37.6 to 46.3), and 926.1 (848.8 to 997.7) per 100 000 population, which were 8.7%, 41.7%, and 39.8% lower than in 1990, respectively. In 2019,…

OBJECTIVE: To develop a reporting guideline for overviews of reviews of healthcare interventions. DESIGN: Development of the preferred reporting items for overviews of reviews (PRIOR) statement. PARTICIPANTS: Core team (seven individuals) led day-to-day operations, and an expert advisory group (three individuals) provided methodological advice. A panel of 100 experts (authors, editors, readers including members of the public or patients) was invited to participate in a modified Delphi exercise. 11 expert panellists (chosen on the basis of expertise, and representing relevant stakeholder groups) were invited to take part in a virtual face-to-face meeting to reach agreement (≥70%) on final checklist items. 21 authors of recently published overviews were invited to pilot test the checklist. SETTING: International consensus. INTERVENTION: Four stage process established by the EQUATOR Network for developing reporting guidelines in health research: project launch (establish a core team and expert advisory group, register intent), evidence reviews (systematic review of published overviews…

OBJECTIVES: To identify data availability, gaps, and patterns for population level prevalence of loneliness globally, to summarise prevalence estimates within World Health Organization regions when feasible through meta-analysis, and to examine temporal trends of loneliness in countries where data exist. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PsycINFO, and Scopus for peer reviewed literature, and Google Scholar and Open Grey for grey literature, supplemented by backward reference searching (to 1 September 2021) ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies based on nationally representative samples (n≥292), validated instruments, and prevalence data for 2000-19. Two researchers independently extracted data and assessed the risk of bias using the Joanna Briggs Institute checklist. Random effects meta-analysis was conducted in the subset of studies with relatively homogeneous research methods by measurement instrument, age group, and WHO region. RESULTS: Prevalence data were available for 113 countries or territories, according…

Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside the uterus, which in many patients is associated with debilitating painful symptoms. Patients with endometriosis are also at greater risk of infertility, emergence of fatigue, multisite pain, and other comorbidities. Thus, endometriosis is best understood as a condition with variable presentation and effects at multiple life stages. A long diagnostic delay after symptom onset is common, and persistence and recurrence of symptoms despite treatment is common. This review discusses the potential genetic, hormonal, and immunologic factors that lead to endometriosis, with a focus on current diagnostic and management strategies for gynecologists, general practitioners, and clinicians specializing in conditions for which patients with endometriosis are at higher risk. It examines evidence supporting the different surgical, pharmacologic, and non-pharmacologic approaches to treating…

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health…

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico, evaluation, but few have yet demonstrated real benefit to patient care. Early stage clinical evaluation is important to assess an AI system’s actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use, and pave the way to further large scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multistakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two round, modified Delphi process to collect and analyse expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 predefined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation &…

OBJECTIVE: To characterise the clinical features of monkeypox infection in humans. DESIGN: Descriptive case series. SETTING: A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022. PARTICIPANTS: 197 patients with polymerase chain reaction confirmed monkeypox infection. RESULTS: The median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71…

Abstract Objective To examine the association of physician burnout with the career engagement and the quality of patient care globally. Design Systematic review and meta-analysis. Data sources Medline, PsycINFO, Embase, and CINAHL were searched from database inception until May 2021. Eligibility criteria for selecting studies Observational studies assessing the association of physician burnout (including a feeling of overwhelming emotional exhaustion, feelings of cynicism and detachment from job defined as depersonalisation, and a sense of ineffectiveness and little personal accomplishment) with career engagement (job satisfaction, career choice regret, turnover intention, career development, and productivity loss) and the quality of patient care (patient safety incidents, low professionalism, and patient satisfaction). Data were double extracted by independent reviewers and checked through contacting all authors, 84 (49%) of 170 of whom confirmed their data. Random-effect models were used to calculate the pooled odds ratio, prediction intervals expressed the amount of…

Abstract Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. Methods A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of…

Abstract Objective To evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. Design Multicentre, randomised, double blind, phase 3 trial. Setting 66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021. Participants 659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment. Intervention Participants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m 2 plus paclitaxel 175 mg/m 2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m 2 continuous infusion on days 1-5). Main outcome measures Overall survival in all patients and in patients with combined positive…

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex,…

OBJECTIVE: To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. DESIGN: Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design. SETTING: Nationwide in the United States. PARTICIPANTS: 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment. INTERVENTIONS: Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence. MAIN OUTCOME MEASURES: The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others. RESULTS: 25 871 participants…

Abstract Objective To estimate associations between COVID-19 vaccination and Long Covid symptoms in adults who were infected with SARS-CoV-2 prior to vaccination. Design Observational cohort study using individual-level interrupted time series analysis. Setting Random sample from the community population of the UK. Participants 28,356 COVID-19 Infection Survey participants (mean age 46 years, 56% female, 89% white) aged 18 to 69 years who received at least their first vaccination after test-confirmed infection. Main outcome measures Presence of long Covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. Results Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (84% of participants). First vaccination was associated with an initial 12.8% decrease (95% confidence interval: −18.6% to −6.6%) in the odds of Long Covid, but increasing by 0.3% (−0.6% to +1.2%) per week after the first dose. Second vaccination was associated with an 8.8% decrease (−14.1% to −3.1%) in the odds…

OBJECTIVE: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. DESIGN: Self-controlled case series and matched cohort study. SETTING: National registries in Sweden. PARTICIPANTS: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. MAIN OUTCOMES MEASURES: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous…

OBJECTIVES: To use data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) to estimate mortality and disability trends for the population aged ≥70 and evaluate patterns in causes of death, disability, and risk factors. DESIGN: Systematic analysis. SETTING: Participants were aged ≥70 from 204 countries and territories, 1990-2019. MAIN OUTCOMES MEASURES: Years of life lost, years lived with disability, disability adjusted life years, life expectancy at age 70 (LE-70), healthy life expectancy at age 70 (HALE-70), proportion of years in ill health at age 70 (PYIH-70), risk factors, and data coverage index were estimated based on standardised GBD methods. RESULTS: Globally the population of older adults has increased since 1990 and all cause death rates have decreased for men and women. However, mortality rates due to falls increased between 1990 and 2019. The probability of death among people aged 70-90 decreased, mainly because of reductions in non-communicable diseases. Globally disability burden was largely driven by functional decline, vision and…

OBJECTIVE: To estimate the risks of incident mental health disorders in survivors of the acute phase of covid-19. DESIGN: Cohort study. SETTING: US Department of Veterans Affairs. PARTICIPANTS: Cohort comprising 153 848 people who survived the first 30 days of SARS-CoV-2 infection, and two control groups: a contemporary group (n=5 637 840) with no evidence of SARS-CoV-2, and a historical control group (n=5 859 251) that predated the covid-19 pandemic. MAIN OUTCOMES MEASURES: Risks of prespecified incident mental health outcomes, calculated as hazard ratio and absolute risk difference per 1000 people at one year, with corresponding 95% confidence intervals. Predefined covariates and algorithmically selected high dimensional covariates were used to balance the covid-19 and control groups through inverse weighting. RESULTS: The covid-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 (95% confidence interval 1.30 to 1.39); risk difference 11.06 (95% confidence interval 9.64 to 12.53) per 1000 people at one year), depressive disorders (1.39 (1.34 to…

OBJECTIVE: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN: Evaluator blinded, randomised controlled trial. SETTING: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control…

OBJECTIVE: To estimate the global burden of type 2 diabetes in adolescents and young adults (aged 15-39 years) from 1990 to 2019. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Disease Study 2019. Participants aged 15-39 years from 204 countries and territories, 1990-2019. MAIN OUTCOMES MEASURES: Age standardised incidence rate, age standardised disability adjusted life years (DALY) rate, and age standardised mortality rate for type 2 diabetes in people aged 15-39 years from 1990 to 2019, and proportional DALY attributable to different risk factors. RESULTS: From 1990 to 2019, significant increases in age standardised incidence rate and age standardised DALY rate were found for type 2 diabetes in adolescents and young adults globally (P<0.001). Age standardised incidence rate (per 100 000 population) increased from 117.22 (95% confidence interval 117.07 to 117.36) in 1990 to 183.36 (183.21 to 183.51) in 2019, and age standardised DALY rate (per 100 000 population) increased from 106.34 (106.20 to 106.48) in 1990 to 149.61 (149.47 to 149.75) in 2019. The age standardised…

Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments. This represents a major step toward destigmatizing the disorder, which was often doubted and deemed untreatable. FND is prevalent, generally affecting young and middle aged adults, and can cause severe disability in some individuals. An early diagnosis, with subsequent access to evidence based rehabilitative and/or psychological treatments, can promote recovery-albeit not all patients respond to currently available treatments. This review presents the latest advances in the use of validated rule-in examination signs to guide diagnosis, and the range of therapeutic approaches available to care for patients with FND. The article focuses on the two most frequently identified subtypes of FND: motor (weakness and/or movement disorders) and seizure type symptoms. Twenty two studies on motor and 27 studies on seizure type symptoms report high specificities of clinical signs (64-100%), and individual signs are reviewed. Rehabilitative interventions…

Abstract Background Post-acute sequelae of SARS-CoV-2 infection have commonly been described after COVID-19, but few population-based studies have examined symptoms six to 12 months after acute SARS-CoV-2 infection and their associations with general health recovery and working capacity. Methods This population-based retrospective cohort study in four geographically defined regions in southern Germany included persons aged 18-65 years with PCR confirmed SARS-CoV-2 infection between October 2020 and March 2021. Symptom frequencies (six to 12 months after versus before acute infection, expressed as prevalence differences [PD] and prevalence ratios [PR]), symptom severity and clustering, risk factors and associations with general health recovery, and working capacity were analysed. Findings Among a total of 11 710 subjects (mean age 44·1 years, 59·8% females, 3·5% previously admitted with COVID-19, mean follow-up time 8.5 months) the most prevalent symptoms with PDs >20% and PRs >5% were rapid physical exhaustion, shortness of breath, concentration difficulties, chronic fatigue, memory…

OBJECTIVE: To present a comprehensive review of the association between measures of body weight, waist, and fat, and different ratios of these measures, and the risk of type 2 diabetes. DESIGN: Systematic review and dose-response meta-analysis of cohort studies. DATA SOURCES: PubMed, Scopus, and Web of Science up to 1 May 2021. REVIEW METHODS: Cohort studies looking at the association between general or central adiposity and body fat content and the risk of type 2 diabetes in the general adult population were included. Two of the authors extracted the data in duplicate. Random effects dose-response meta-analyses were performed to estimate the degree of the associations. Curvilinear associations were modelled with a one stage weighted mixed effects meta-analysis. RESULTS: 216 cohort studies with 2.3 million individuals with type 2 diabetes among 26 million participants were identified. Relative risks were 1.72 (95% confidence interval 1.65 to 1.81; n=182 studies) for an increase in body mass index of 5 units, 1.61 (1.52 to 1.70; n=78) for a 10 cm larger waist circumference, 1.63…

OBJECTIVES: To study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease). DESIGN: Population based prospective cohort study (2009-21). SETTING: France, primary prevention research. PARTICIPANTS: 103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products. MAIN OUTCOMES MEASURES: Associations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models. RESULTS: Total artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18,…

OBJECTIVE: To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection. DESIGN: Retrospective cohort study. SETTING: UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results. PARTICIPANTS: Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490). MAIN OUTCOME MEASURES: revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was…

OBJECTIVE: To determine the comparative effectiveness and safety of psychological interventions for chronic low back pain. DESIGN: Systematic review with network meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, and CINAHL from database inception to 31 January 2021. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials comparing psychological interventions with any comparison intervention in adults with chronic, non-specific low back pain. Two reviewers independently screened studies, extracted data, and assessed risk of bias and confidence in the evidence. Primary outcomes were physical function and pain intensity. A random effects network meta-analysis using a frequentist approach was performed at post-intervention (from the end of treatment to <2 months post-intervention); and at short term (≥2 to <6 months post-intervention), mid-term (≥6 to <12 months post-intervention), and long term follow-up (≥12 months post-intervention). Physiotherapy care was the reference comparison…

Abstract Objective To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021. Review methods Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included. Data extraction and synthesis Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the…

The randomised trial is the preferred study design for evaluating the effectiveness and safety of interventions. Yet such trials can be prohibitively expensive, unethical, or take too long. When it is not possible to carry out a randomised trial, observational data can be used to answer similar questions. Here, we describe the process of using observational data to emulate a target trial, which applies the study design principles of randomised trials to observational studies that aim to estimate the causal effect of an intervention. The target trial provides a formal framework to help avoid self-inflicted biases common to observational studies.

Persistent human papillomavirus infection is the central cause of cervical cancer, the leading cause of cancer death among women worldwide. Clear evidence from both randomized trials and population based studies shows that vaccination against human papillomavirus reduces the incidence of cervical pre-cancer. These data suggest that the vaccine reduces the incidence of cervical cancer. However, human papillomavirus vaccine coverage is inadequate in all countries, especially in low and middle income countries where disease burden is highest. Supply side strategies to improve coverage include increasing the availability of low cost vaccines, school located delivery, single dose vaccine schedules, and development of vaccines that do not need refrigeration. Demand side strategies include enhancing provider recommendations, correcting misinformation, and public awareness campaigns. The near elimination of cervical cancer is achievable through increased uptake of human papillomavirus vaccination and efforts to increase screening for cervical cancer, especially when enacted to reduce…

OBJECTIVE: To quantify the risk of overall and type specific cardiovascular and cerebrovascular diseases as well as venous thromboembolism in women with a history of gestational diabetes mellitus. DESIGN: Systematic review and meta-analyses. DATA SOURCES: PubMed, Embase, and the Cochrane Library from inception to 1 November 2021 and updated on 26 May 2022. REVIEW METHODS: Observational studies reporting the association between gestational diabetes mellitus and incident cardiovascular and cerebrovascular diseases were eligible. Data, pooled by random effects models, are presented as risk ratios (95% confidence intervals). Certainty of evidence was appraised by the Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: 15 studies rated as moderate or serious risk of bias were included. Of 513 324 women with gestational diabetes mellitus, 9507 had cardiovascular and cerebrovascular disease. Of more than eight million control women without gestational diabetes, 78 895 had cardiovascular and cerebrovascular disease. Compared with women without gestational diabetes…

OBJECTIVE: To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States. DESIGN: Observational study. SETTING: US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021. PARTICIPANTS: Residents of 2558 counties from 48 US states. MAIN OUTCOME MEASURES: The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared. RESULTS: In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county…

OBJECTIVE: To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status. DESIGN: Test negative case-control study. SETTING: Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022. PARTICIPANTS: 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2. MAIN OUTCOME MEASURES: The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated. RESULTS: 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested…

Abstract Objective To assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). Design Retrospective cohort study. Setting England, UK, 1 December 2021 to 25 January 2022. Participants 1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible. Main outcome measures Death involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age,…

Abstract Objective To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group. Design Prospective, double blind, superiority, randomised placebo controlled trial. Setting Seven French teaching hospitals between 13 April 2015 and 12 March 2019. Eligibility criteria for participants Aged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine. Participants 156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders. Intervention Two 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment. Main outcome measures The primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3.…

OBJECTIVES: To investigate the survival benefit of transplantation versus dialysis for waitlisted kidney failure patients with a priori stratification. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Online databases MEDLINE, Ovid Embase, Web of Science, Cochrane Collection, and ClinicalTrials.gov were searched between database inception and 1 March 2021. INCLUSION CRITERIA: All comparative studies that assessed all cause mortality for transplantation versus dialysis in patients with kidney failure waitlisted for transplant surgery were included. Two independent reviewers extracted the data and assessed the risk of bias of included studies. Meta-analysis was done using the DerSimonian-Laird random effects model, with heterogeneity investigated by subgroup analyses, sensitivity analyses, and meta-regression. RESULTS: The search identified 48 observational studies with no randomised controlled trials (n=1 245 850 patients). In total, 92% (n=44/48) of studies reported a long term (at least one year) survival benefit associated with transplantation compared with dialysis.…

Abstract Objective To examine the effectiveness of physical activity interventions delivered or prompted by primary care health professionals for increasing moderate to vigorous intensity physical activity (MVPA) in adult patients. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Databases (Medline and Medline in progress, Embase, PsycINFO, CINAHL, SPORTDiscus, Sports Medicine and Education Index, ASSIA, PEDro, Bibliomap, Science Citation Index, Conference Proceedings Citation Index), trial registries (Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, TRoPHI), and grey literature (OpenGrey) sources were searched (from inception to September 2020). Eligibility criteria for selecting studies Randomised controlled trials of aerobic based physical activity interventions delivered or prompted by health professionals in primary care with a usual care control group or another control group that did not involve physical activity. Study selection and analysis Two independent reviewers screened the search results, extracted data from…

Nenggui Xu and colleagues call for more effective evidence dissemination of and research into promising acupuncture therapies

What you need to know • Long covid (prolonged symptoms following covid-19 infection) is common • The mainstay of management is supportive, holistic care, symptom control, and detection of treatable complications • Many patients can be supported effectively in primary care by a GP with a special interest This article updates and extends a previous BMJ Practice Pointer published in August 2020 when almost no peer reviewed research or evidence based guidance on the condition was available.1 In this update we outline how clinicians might respond to the questions that patients ask.

OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to…

OBJECTIVE: To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis. DESIGN: Systematic review and meta-analysis of randomised trials. DATA SOURCES: Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment. MAIN OUTCOME MEASURES: The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was -0.37 SMD. Serious adverse events were analysed as relative risks. METHODS: Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias…

OBJECTIVE: To assess the effects of plasma exchange on important outcomes in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). DESIGN: Systematic review and meta-analysis of randomised controlled trials. ELIGIBILITY CRITERIA: Randomised controlled trials investigating effects of plasma exchange in patients with AAV or pauci-immune rapidly progressive glomerulonephritis and at least 12 months' follow-up. INFORMATION SOURCES: Prior systematic reviews, updated by searching Medline, Embase, and CENTRAL to July 2020. RISK OF BIAS: Reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. SYNTHESIS OF RESULTS: Meta-analyses were conducted using random effects models to calculate risk ratios and 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. Outcomes were assessed after at least12 months of follow-up and included all-cause mortality, end stage kidney disease (ESKD), serious infections, disease relapse, serious adverse events, and quality of life.…

OBJECTIVE: To assess whether percutaneous transforaminal endoscopic discectomy (PTED) is non-inferior to conventional open microdiscectomy in reduction of leg pain caused by lumbar disc herniation. DESIGN: Multicentre randomised controlled trial with non-inferiority design. SETTING: Four hospitals in the Netherlands. PARTICIPANTS: 613 patients aged 18-70 years with at least six weeks of radiating leg pain caused by lumbar disc herniation. The trial included a predetermined set of 125 patients receiving PTED who were the learning curve cases performed by surgeons who did not do PTED before the trial. INTERVENTIONS: PTED (n=179) compared with open microdiscectomy (n=309). MAIN OUTCOME MEASURES: The primary outcome was self-reported leg pain measured by a 0-100 visual analogue scale at 12 months, assuming a non-inferiority margin of 5.0. Secondary outcomes included complications, reoperations, self-reported functional status as measured with the Oswestry Disability Index, visual analogue scale for back pain, health related quality of life, and self-perceived recovery. Outcomes were…

OBJECTIVES: To describe retracted papers originating from paper mills, including their characteristics, visibility, and impact over time, and the journals in which they were published. DESIGN: Cross sectional study. SETTING: The Retraction Watch database was used for identification of retracted papers from paper mills, Web of Science was used for the total number of published papers, and data from Journal Citation Reports were collected to show characteristics of journals. PARTICIPANTS: All paper mill papers retracted from 1 January 2004 to 26 June 2022 were included in the study. Papers bearing an expression of concern were excluded. MAIN OUTCOME MEASURES: Descriptive statistics were used to characterise the sample and analyse the trend of retracted paper mill papers over time, and to analyse their impact and visibility by reference to the number of citations received. RESULTS: 1182 retracted paper mill papers were identified. The publication of the first paper mill paper was in 2004 and the first retraction was in 2016; by 2021, paper mill retractions accounted for 772 (21.8%) of…

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The…

OBJECTIVE: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN: Observational study. SETTING: 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS: ) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS: O during the first 10 days of mechanical ventilation. CONCLUSIONS: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and…

OBJECTIVE: To compare maternal mortality in eight countries with enhanced surveillance systems. DESIGN: Descriptive multicountry population based study. SETTING: Eight countries with permanent surveillance systems using enhanced methods to identify, document, and review maternal deaths. The most recent available aggregated maternal mortality data were collected for three year periods for France, Italy, and the UK and for five year periods for Denmark, Finland, the Netherlands, Norway, and Slovakia. POPULATION: 297 835 live births in Denmark (2013-17), 301 169 in Finland (2008-12), 2 435 583 in France (2013-15), 1 281 986 in Italy (2013-15), 856 572 in the Netherlands (2014-18), 292 315 in Norway (2014-18), 283 930 in Slovakia (2014-18), and 2 261 090 in the UK (2016-18). OUTCOME MEASURES: Maternal mortality ratios from enhanced systems were calculated and compared with those obtained from each country's office of vital statistics. Age specific maternal mortality ratios; maternal mortality ratios according to women's origin, citizenship, or ethnicity; and cause specific maternal…

OBJECTIVE: To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN: Network meta-analysis. DATA SOURCES: Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES: We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated…

OBJECTIVE: To examine the association between consumption of ultra-processed foods and risk of colorectal cancer among men and women from three large prospective cohorts. DESIGN: Prospective cohort study with dietary intake assessed every four years using food frequency questionnaires. SETTING: Three large US cohorts. PARTICIPANTS: Men (n= 46 341) from the Health Professionals Follow-up Study (1986-2014) and women (n=159 907) from the Nurses' Health Study (1986-2014; n=67 425) and the Nurses' Health Study II (1991-2015; n=92 482) with valid dietary intake measurement and no cancer diagnosis at baseline. MAIN OUTCOME MEASURE: Association between ultra-processed food consumption and risk of colorectal cancer, estimated using time varying Cox proportional hazards regression models adjusted for potential confounding factors. RESULTS: 3216 cases of colorectal cancer (men, n=1294; women, n=1922) were documented during the 24-28 years of follow-up. Compared with those in the lowest fifth of ultra-processed food consumption, men in the highest fifth of consumption had a 29% higher risk of…

Abstract Objectives Myocarditis and pericarditis are adverse events of special interest after vaccination for COVID-19. Evidence syntheses were conducted on incidence rates, risk factors for myocarditis and pericarditis after COVID-19 mRNA vaccination, clinical presentation and short- and longer-term outcomes of cases, and proposed mechanisms and their supporting evidence. Design Systematic reviews and evidence reviews. Data sources Medline, Embase and the Cochrane Library were searched from October 2020 to January 10, 2022; reference lists and grey literature (to January 13, 2021). Review methods Large (>10,000) or population-based/multisite observational studies and surveillance data (incidence and risk factors) reporting on confirmed myocarditis or pericarditis after COVID-19 vaccination; case series (n≥5, presentation, short-term clinical course and longer-term outcomes); opinions/letters/reviews/primary studies focused on describing or supporting hypothesized mechanisms. A single reviewer completed screening and another verified 50% of exclusions, using a machine-learning…

OBJECTIVES: To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant. DESIGN: Test negative design. SETTING: Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022. PARTICIPANTS: After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included. MAIN OUTCOME MEASURES: Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously.…

OBJECTIVE: To evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and death. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 databases, including 38 sources of published studies and preprints. STUDY SELECTION: Randomised controlled trials, cohort studies, and case-control studies. METHODS: 38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022 to 31 July 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1−odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the…

OBJECTIVE: To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC). DESIGN: Multiphase, prospective mixed methods study. SETTING: Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021. PARTICIPANTS: 13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire. MAIN OUTCOME MEASURES: Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale…

### What you need to know Extreme preterm birth, defined as birth before 28 weeks’ gestational age (box 1),1 affects about two to five in every 1000 pregnancies, and varies slightly by country and by definitions used. Severe maternal morbidity, including sepsis and peripartum haemorrhage, affects around a quarter of mothers delivering at these gestations.2 For the babies, survival and morbidity rates vary, particularly by gestational age at delivery but also according to other risk factors (birth weight and sex, for example) and by country.34 In this update, we focus on high income countries and provide a broad overview of extreme preterm birth epidemiology, recent changes, and best practices in obstetric and neonatal management, including new treatments such as antenatal magnesium sulphate or changes in delivery management such as delayed cord clamping and placental transfusion. We cover short and long term medical, psychological, and experiential consequences for individuals born extremely preterm, their mothers and families, as well as preventive measures that may reduce the…

OBJECTIVE: To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer. DESIGN: Prospectively registered systematic review and meta-analysis of literature. DATA SOURCES: Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors. ELIGIBILITY CRITERIA: Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm). RESULTS: 68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence…

OBJECTIVE: To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty. DESIGN: Randomised, blinded, placebo controlled trial with follow-up at 90 days. SETTING: Five Danish hospitals, September 2018 to March 2020. PARTICIPANTS: 485 adult participants undergoing total knee arthroplasty. INTERVENTION: A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia. MAIN OUTCOME MEASURES: The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain.…

Nicola M McKeown and colleagues advocate for the importance of translating the health impact of high fibre diets to patients and clients, with emphasis placed on incorporating a variety of plant based foods to achieve dietary fibre recommendations

OBJECTIVE: To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022. DESIGN: Contact tracing study, linking data on case-contact pairs and on probable exposure dates. SETTING: Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom. PARTICIPANTS: 2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022. MAIN OUTCOME MEASURES: The incubation period and serial interval of a monkeypox infection using two bayesian time delay models-one corrected for interval censoring (ICC-interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC-interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models. RESULTS: The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of…

OBJECTIVE: To determine the effect of the introduction of low dose computed tomography screening in 2013 on lung cancer stage shift, survival, and disparities in the stage of lung cancer diagnosed in the United States. DESIGN: Quasi-experimental study using Joinpoint modeling, multivariable ordinal logistic regression, and multivariable Cox proportional hazards modeling. SETTING: US National Cancer Database and Surveillance Epidemiology End Results program database. PARTICIPANTS: Patients aged 45-80 years diagnosed as having non-small cell lung cancer (NSCLC) between 1 January 2010 and 31 December 2018. MAIN OUTCOME MEASURES: Annual per cent change in percentage of stage I NSCLC diagnosed among patients aged 45-54 (ineligible for screening) and 55-80 (potentially eligible for screening), median all cause survival, and incidence of NSCLC; multivariable adjusted odds ratios for year-to-year changes in likelihood of having earlier stages of disease at diagnosis and multivariable adjusted hazard ratios for changes in hazard of death before versus after introduction of screening.…

Abstract Objectives To evaluate measurement discrepancies by race between pulse oximetry and arterial oxygen saturation (as measured in arterial blood gas) among inpatients not in intensive care. Design Multicenter, retrospective cohort study using electronic medical records from general care medical and surgical inpatients. Setting Veteran Health Administration, a national and racially diverse integrated health system in the United States, from 2013 to 2019. Participants Adult inpatients in general care (medical and surgical), in Veteran Health Administration medical centers. Main outcomes measures Occult hypoxemia (defined as arterial blood oxygen saturation (SaO 2 ) of <88% despite a pulse oximetry (SpO 2 ) reading of ≥92%), and whether rates of occult hypoxemia varied by race and ethnic origin. Results A total of 30 039 pairs of SpO 2 -SaO 2 readings made within 10 minutes of each other were identified during the study. These pairs were predominantly among non-Hispanic white (21 918 (73.0%)) patients; non-Hispanic black patients and Hispanic or Latino patients accounted for 6498…

OBJECTIVE: To examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia. DESIGN: Prospective cohort study. SETTING: Civil service departments in London (Whitehall II study, study inception in 1985-88). PARTICIPANTS: 10 095 participants, aged 35 to 55 at baseline. MAIN OUTCOME MEASURE: Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death. RESULTS: The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95%…

Pregnancy is an independent risk factor for severe covid-19. Vaccination is the best way to reduce the risk for SARS-CoV-2 infection and limit its morbidity and mortality. The current recommendations from the World Health Organization, Centers for Disease Control and Prevention, and professional organizations are for pregnant, postpartum, and lactating women to receive covid-19 vaccination. Pregnancy specific considerations involve potential effects of vaccination on fetal development, placental transfer of antibodies, and safety of maternal vaccination. Although pregnancy was an exclusion criterion in initial clinical trials of covid-19 vaccines, observational data have been rapidly accumulating and thus far confirm that the benefits of vaccination outweigh the potential risks. This review examines the evidence supporting the effectiveness, immunogenicity, placental transfer, side effects, and perinatal outcomes of maternal covid-19 vaccination. Additionally, it describes factors associated with vaccine hesitancy in pregnancy. Overall, studies monitoring people who have received…

Objective To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment. Design Systematic review and meta-analysis Data sources PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021. Review methods Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of…

Monkeypox, a virus first discovered in monkeys in 1958 and that spread to humans in 1970, is now being seen in small but rising numbers in Western Europe and North America. Elisabeth Mahase summarises what we know so far

Abstract Objectives To characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016. Design Individual participant data analysis. Population 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants. Main outcome measures Responses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models. Results The random effects mean difference between drug and placebo favored drug (1.75 points, 95%…

Similarly to idiopathic pulmonary fibrosis (IPF), other interstitial lung diseases can develop progressive pulmonary fibrosis (PPF) characterized by declining lung function, a poor response to immunomodulatory therapies, and early mortality. The pathophysiology of disordered lung repair involves common downstream pathways that lead to pulmonary fibrosis in both IPF and PPF. The antifibrotic drugs, such as nintedanib, are indicated for the treatment of IPF and PPF, and new therapies are being evaluated in clinical trials. Clinical, radiographic, and molecular biomarkers are needed to identify patients with PPF and subgroups of patients likely to respond to specific therapies. This article reviews the evidence supporting the use of specific therapies in patients with IPF and PPF, discusses agents being considered in clinical trials, and considers potential biomarkers based on disease pathogenesis that might be used to provide a personalized approach to care.

Chronic pain conditions are common and have a considerable impact on health and wellbeing. This impact can be reduced by cognitive behavioral therapy (CBT), the most commonly applied psychological approach to chronic pain. At the same time, CBT continues to develop, and now includes what is sometimes called "third wave" CBT. In this review, we examine the evidence for application of acceptance and commitment therapy (ACT), a principal example of this new wave or latest generation of treatment approaches, in people with chronic pain. We identified 25 randomized controlled trials of ACT for adults with chronic pain. Across the included trials, small to large effect sizes favoring ACT were reported for key outcomes including pain interference, disability, depression, and quality of life. Evidence from three studies provided some support for the cost effectiveness of ACT for chronic pain. Evidence also supported the mediating role of theoretically consistent processes of change (psychological flexibility) in relation to treatment outcomes. Investigation of moderators and predictors of…

OBJECTIVES: To evaluate the potential for long distance airborne transmission of SARS-CoV-2 in indoor community settings and to investigate factors that might influence transmission. DESIGN: Rapid systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, medRxiv, Arxiv, and WHO COVID-19 Research Database for studies published from 27 July 2020 to 19 January 2022; existing relevant rapid systematic review for studies published from 1 January 2020 to 27 July 2020; and citation analysis in Web of Science and Cocites. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Observational studies reporting on transmission events in indoor community (non-healthcare) settings in which long distance airborne transmission of SARS-CoV-2 was the most likely route. Studies such as those of household transmission where the main transmission route was likely to be close contact or fomite transmission were excluded. DATA EXTRACTION AND SYNTHESIS: Data extraction was done by one reviewer and independently checked by a second reviewer. Primary outcomes were SARS-CoV-2 infections through long…

OBJECTIVES: To compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids, nutritional supplements (zinc), progesterone (intramuscular, oral, or vaginal), prophylactic antibiotics, prophylactic tocolytics, combinations of interventions, placebo or no treatment (control) to prevent spontaneous preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth or short cervical length. DESIGN: Systematic review with bayesian network meta-analysis. DATA SOURCES: The Cochrane Pregnancy and Childbirth Group's Database of Trials, the Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of pregnant women who are at high risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. No language or date restrictions were applied. OUTCOMES: Seven maternal…

OBJECTIVE: To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics. DESIGN: Multicentre, open label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. MAIN OUTCOME MEASURE: Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months. RESULTS:…

OBJECTIVE: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events. DESIGN: Population based historical rate comparison study and self-controlled case series analysis. SETTING: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data. PARTICIPANTS: 8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population. MAIN OUTCOME MEASURES: Outcomes were incidence of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test…

Yu-Tong Fei and colleagues examine the problems with designing and implementing trials of acupuncture

OBJECTIVE: To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States. DESIGN: Multicenter observational case-control study with a test negative design. SETTING: Hospitals in 18 US states. PARTICIPANTS: 4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls). MAIN OUTCOME MEASURES: The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary…

Abstract Objective To examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care. Design Systematic review and meta-analysis of randomised controlled trials. Eligibility criteria for selection of studies Randomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up. Data sources Trials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021. Data extraction and synthesis Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated. Main outcome measures Primary…

Gavin Yamey and colleagues say that a new, urgent push for global vaccine equity could help avert suffering and deaths, protect economies, and prevent new virus variants

ABSTRACT OBJECTIVES To determine whether population-level implementation of a test-and- treat approach to correction of sub-optimal vitamin D status (25-hydroxyvitamin D [25(OH)D] <75 nmol/L) influences risk of all-cause acute respiratory infection (ARI) or coronavirus disease 2019 (COVID-19). DESIGN Phase 3 open-label randomised controlled trial (CORONAVIT) utilising trials-within-cohorts (TwiCs) methodology. SETTING United Kingdom. PARTICIPANTS 6200 adults aged 16 years or older, who were not already taking vitamin D supplements at baseline. INTERVENTIONS Offer of a postal finger-prick test of blood 25(OH)D concentration with provision of a 6-month supply of higher-dose vitamin D (3200 IU/day, n=1550) or lower-dose vitamin D (800 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). Follow-up was from 17 th December 2020 to 16 th June 2021. MAIN OUTCOME MEASURES The primary outcome was the proportion of participants experiencing at least one doctor- or swab test-confirmed ARI of any cause. Secondary outcomes…

OBJECTIVES: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. DESIGN: Retrospective cohort study. SETTING: Italy, 27 December 2020 to 7 November 2021. PARTICIPANTS: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference.…

Abstract Objective To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes. Design Population based cohort study using an active comparator, new user design. Setting The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. Participants Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14 259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third…

Approaches to youth development that enhance connectedness and opportunities for young people are key to adolescent health and wellbeing argue Robert Blum and colleagues

Better understanding is essential for health system planning

Thorough validation is pivotal for any prediction model before it can be advocated for use in medical practice. For time-to-event outcomes such as breast cancer recurrence, death from other causes is a competing risk. Model performance measures must account for such competing events. In this article, we present a comprehensive yet accessible overview of performance measures for this competing event setting, including the calculation and interpretation of statistical measures for calibration, discrimination, overall prediction error, and clinical usefulness by decision curve analysis. All methods are illustrated for patients with breast cancer, with publicly available data and R code.

Chronic migraine is a neurologic disorder associated with considerable disability, lost productivity, and a profound economic burden worldwide. The past five years have seen a dramatic expansion in new treatments for this often challenging condition, among them calcitonin gene related peptide antagonists and neuromodulatory devices. This review outlines the epidemiology of and diagnostic criteria and risk factors for chronic migraine. It discusses evidence based drug and non-drug treatments, their advantages and disadvantages, and the principles of patient centered care for adults with chronic migraine, with attention to differential diagnosis and comorbidities, clinical reasoning, initiation and monitoring, cost, and availability. It discusses the international guidelines on drug treatment for chronic migraine and evaluates non-drug treatments including behavioral and complementary therapies and lifestyle modifications. Finally, it discusses the management of chronic migraine in special populations, including pediatrics, pregnancy, and older people, and considers future questions…

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for…

Review of gender identity services for children and young people Hilary Cass chairIndependent Review into Gender Identity Services for Children and Young PeopleContemporary clinical practice presents us with day-to-day challenges which are a far cry from many of the didactic topics we covered at medical school.These include advising on treatment options when the underpinning evidence base is weak, complex issues of risk and safeguarding, ethical dilemmas about how to ensure best interests of vulnerable individuals, service safety in the face of workforce shortages, and polarised societal views on what the NHS can and should do.Clinicians working with children and young people with gender-related distress face every one of these dilemmas.

OBJECTIVES: To evaluate the effectiveness of an intervention, with and without a height adjustable desk, on daily sitting time, and to investigate the relative effectiveness of the two interventions, and the effectiveness of both interventions on physical behaviours and physical, biochemical, psychological, and work related health and performance outcomes. DESIGN: Cluster three arm randomised controlled trial with follow-up at three and 12 months. SETTING: Local government councils in Leicester, Liverpool, and Greater Manchester, UK. PARTICIPANTS: 78 clusters including 756 desk based employees in defined offices, departments, or teams from two councils in Leicester, three in Greater Manchester, and one in Liverpool. INTERVENTIONS: Clusters were randomised to one of three conditions: the SMART Work and Life (SWAL) intervention, the SWAL intervention with a height adjustable desk (SWAL plus desk), or control (usual practice). MAIN OUTCOMES MEASURES: The primary outcome measure was daily sitting time, assessed by accelerometry, at 12 month follow-up. Secondary outcomes were…

OBJECTIVES: To determine the prevalence and frequency of using any tobacco product and each of a detailed set of tobacco products, how tobacco use and frequency of use vary across countries, world regions, and World Bank country income groups, and the socioeconomic and demographic gradients of tobacco use and frequency of use within countries. DESIGN: Secondary analysis of nationally representative, cross-sectional, household survey data from 82 low and middle income countries collected between 1 January 2015 and 31 December 2020. SETTING: Population based survey data. PARTICIPANTS: 1 231 068 individuals aged 15 years and older. MAIN OUTCOME MEASURES: Self-reported current smoking, current daily smoking, current smokeless tobacco use, current daily smokeless tobacco use, pack years, and current use and use frequencies of each tobacco product. Products were any type of cigarette, manufactured cigarette, hand rolled cigarette, water pipe, cigar, oral snuff, nasal snuff, chewing tobacco, and betel nut (with and without tobacco). RESULTS: The smoking prevalence in the study sample was…

OBJECTIVE: To describe the association between mistreatment, burnout, and having multiple marginalized identities during undergraduate medical education. DESIGN: Cross sectional survey and retrospective cohort study. SETTING: 140 US medical schools accredited by the Association of American Medical Colleges. PARTICIPANTS: 30 651 graduating medical students in 2016 and 2017. MAIN OUTCOME MEASURES: Self-reported sex, race or ethnicity, and sexual orientation groups were considered, based on the unique combinations of historically marginalized identities held by students. Multivariable linear regression was used to determine the association between unique identity groups and burnout along two dimensions (exhaustion and disengagement) as measured by the Oldenburg Burnout Inventory for Medical Students while accounting for mistreatment and discrimination. RESULTS: Students with three marginalized identities (female; non-white; lesbian, gay, or bisexual (LGB)) had the largest proportion reporting recurrent experiences of multiple types of mistreatment (88/299, P<0.001) and discrimination…

OBJECTIVE: To estimate the effectiveness of physical activity monitor (PAM) based interventions among adults and explore reasons for the heterogeneity. DESIGN: Systematic review and meta-analysis. STUDY SELECTION: The electronic databases MEDLINE, Embase, SPORTDiscus, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on 4 June 2021. Eligible randomised controlled trials compared interventions in which adults received feedback from PAMs with control interventions in which no feedback was provided. No restrictions on type of outcome measurement, publication date, or language were applied. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were used to synthesise the results. The certainty of evidence was rated by the Grading of Recommendations Assessment and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: The three primary outcomes of interest were physical activity, moderate to vigorous physical activity, and sedentary time. RESULTS: 121 randomised controlled trials…

OBJECTIVE: To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England. DESIGN: Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England. SETTING: Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data. POPULATION: Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021. MAIN OUTCOME MEASURES: For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020. RESULTS: After 1 March 2020, substantial…

Rapid, convenient, and full access to personal electronic health records is a key part of empowering patients to manage their health and collaborate with healthcare, argue Maria Hägglund and colleagues

OBJECTIVE: To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, and Embase from inception to 1 December 2021. REVIEW METHODS: Randomised controlled trials comparing different types and intensities of statins, including placebo, in adults with type 1 or type 2 diabetes mellitus were included. The primary outcome was changes in levels of non-HDL-C, calculated from measures of total cholesterol and HDL-C. Secondary outcomes were changes in levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, three point major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and death related to cardiovascular disease), and discontinuations because of adverse events. A bayesian network meta-analysis of statin intensity (low, moderate, or high) with random effects evaluated the…

Testicular cancer is a curable cancer. The success of physicians in curing the disease is underpinned by multidisciplinary advances. Cisplatin-based combination chemotherapy and the refinement of post-chemotherapy surgical procedures and diagnostic strategies have greatly improved long term survival in most patients. Despite such excellent outcomes, several controversial dilemmas exist in the approaches to clinical stage I disease, salvage chemotherapy, post-chemotherapy surgical procedures, and implementing innovative imaging studies. Relapse after salvage chemotherapy has a poor prognosis and the optimal treatment is not apparent. Recent research has provided insight into the molecular mechanisms underlying cisplatin resistance. Phase 2 studies with targeted agents have failed to show adequate efficacy; however, our understanding of cisplatin resistant disease is rapidly expanding. This review summarizes recent advances and discusses relevant issues in the biology and management of testicular cancer.

In survival analysis, competing events preclude the occurrence of the event of interest. The censoring of competing events is common in medical studies but leads to biased cumulative incidence estimators. Competing risks methods, such as the non-parametric Aalen-Johansen method or the semi-parametric Fine and Gray model, alleviate this bias and should be preferred above the Kaplan-Meier method and the Cox model, respectively. As an illustrative example, in a large European cohort, we report on the differences in the cumulative incidence estimates of graft failure after kidney transplantation, caused by censoring for recipient death.

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary…

Neuropsychiatric symptoms (NPSs) such as affective disorders, psychosis, behavioral changes, and cognitive impairment are common in Parkinson's disease (PD). However, NPSs remain under-recognized and under-treated, often leading to adverse outcomes. Their epidemiology, presentation, risk factors, neural substrate, and management strategies are incompletely understood. While psychological and psychosocial factors may contribute, hallmark PD neuropathophysiological changes, plus the associations between exposure to dopaminergic medications and occurrence of some symptoms, suggest a neurobiological basis for many NPSs. A range of psychotropic medications, psychotherapeutic techniques, stimulation therapies, and other non-pharmacological treatments have been studied, are used clinically, and are beneficial for managing NPSs in PD. Appropriate management of NPSs is critical for comprehensive PD care, from recognizing their presentations and timing throughout the disease course, to the incorporation of different therapeutic strategies (ie, pharmacological and non-pharmacological) that…

OBJECTIVE: , can reduce the development of type 2 diabetes among adults with impaired glucose tolerance. DESIGN: Double blinded, multicentre, randomised, placebo controlled trial. SETTING: Three hospitals in Japan, between June 2013 and August 2019. PARTICIPANTS: People aged 30 years and older who had impaired glucose tolerance defined by using a 75 g oral glucose tolerance test and glycated haemoglobin level. INTERVENTIONS: Participants were randomised to receive active vitamin D (eldecalcitol 0.75 μg per day; n=630) or matching placebo (n=626) for three years. MAIN OUTCOMES: The primary endpoint was incidence of diabetes. Prespecified secondary endpoints were regression to normoglycaemia and incidence of type 2 diabetes after adjustment for confounding factors at baseline. In addition, bone densities and bone and glucose metabolism markers were assessed. RESULTS: Of the 1256 participants, 571 (45.5%) were women and 742 (59.1%) had a family history of type 2 diabetes. The mean age of participants was 61.3 years. The mean serum 25-hydroxyvitamin D concentration at baseline was 20.9…

### What you need to know Gout is a painful and debilitating condition with long term complications, including joint damage and renal stones. Although gout flares are often treated with NSAIDs, colchicine or steroids, those with gout often continue to have flares which could have been prevented with lifestyle modification or urate lowering medication. However, only a third of people with gout receive urate lowering therapies (ULTs), and only a third of those have their serum urate level managed effectively.1 This article summarises the recommendations from the new National Institute for Health and Care Excellence (NICE) guideline, focusing on the diagnosis and management of gout.2 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Committee’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Diagnosis and assessment Most people with gout…

OBJECTIVE: To examine the relative effectiveness of a fourth dose of the Pfizer-BioNTech mRNA (BNT162b2) vaccine compared with three vaccine doses over the span of 10 weeks. DESIGN: Retrospective, test negative, case-control study, with a matched analysis and an unmatched multiple tests analysis. SETTING: Nationally centralised database of Maccabi Healthcare Services, an Israeli national health fund for 2.5 million people; from 10 January 2022 (seven days after the fourth dose was first given to eligible individuals) to 13 March 2022, an omicron dominant period in Israel. PARTICIPANTS: 97 499 Maccabi Healthcare Services members aged 60 years and older, who were eligible to receive a fourth vaccine dose and obtained at least one polymerase chain reaction (PCR) test during the study. MAIN OUTCOME MEASURES: Breakthrough SARS-CoV-2 infection, defined as a positive PCR test performed seven or more days after inoculation with the BNT162b2 vaccine; and breakthrough SARS-CoV-2 infection resulting in severe covid-19 disease, defined as hospital admission or death related to covid-19.…

OBJECTIVE: To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19. DESIGN: Observational cohort study with the OpenSAFELY platform. SETTING: With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings. PARTICIPANTS: Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.…

Systematic reviews should incorporate as much relevant evidence as possible to reduce bias and research waste and increase reliability of results. Clinical trials registers are a key resource for identifying potentially eligible studies, particularly those that are unpublished, and therefore searching these registers is mandated for best practice systematic reviews. However, the process of searching can be challenging and no clear and consistent guidance on how best to do this exists. This paper provides step-by-step guidance on how to conduct systematic searches for studies using clinical trials registers, with a case study to illustrate each step. The guidance encompasses where to search and how to formulate the search strategy, conduct the search, download results, screen records, obtain data, update searches, and report on these searches.

OBJECTIVE: To identify drug classes and individual selective serotonin reuptake inhibitors (SSRIs) with high rates of remission and low risk of adverse events in the treatment of panic disorder with or without agoraphobia. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Medline, and ClinicalTrials.gov from inception to 17 June 2021. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials that included adults aged ≥18 years with a diagnosis of panic disorder, compared drugs used to treat the panic disorder, and measured the outcomes of interest, including remissions, dropouts, and adverse events. METHODS: Risk of bias in the included studies was assessed using the revised Cochrane risk of bias tool for randomised trials. Direct meta-analyses were performed using random effects models. A two stage network meta-analysis with surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of drug classes and individual SSRIs. RESULTS: 87 studies including a total of 12 800 participants and 12 drug classes were…

OBJECTIVE: To jointly analyse two food dimensions, the Food Standards Agency Nutrient Profiling System (FSAm-NPS), used to derive the Nutri-Score front-of-pack label, and the NOVA classification in relation to mortality. DESIGN: Prospective cohort study. SETTING: Moli-sani Study, Italy 2005-10. PARTICIPANTS: 22 895 participants (mean age 55 (SD 12) years; 48% men). MAIN OUTCOMES MEASURES: Associations between dietary exposures and mortality risk, assessed using multivariable cause specific Cox proportional hazard models controlled for known risk factors. RESULTS: A total of 2205 deaths occurred during 272 960 person years of follow-up. In the highest quarter of the FSAm-NPS index compared with the lowest quarter, multivariable adjusted hazard ratios for all cause and cardiovascular mortality were 1.19 (95% confidence interval 1.04 to 1.35; absolute risk difference 4.3%, 95% confidence interval 1.4% to 7.2%) and 1.32 (1.06 to 1.64; 2.6%, 0.3% to 4.9%), respectively. The hazard ratios were 1.19 (1.05 to 1.36; absolute risk difference 9.7%, 5.0% to 14.3%) and 1.27 (1.02 to 1.58; 5.0%,…