EClinicalMedicine最新文献

Background: Disease outbreaks significantly affect maternal and neonatal health. Variability in reporting health outcomes hinder evidence generation. We aimed to develop a core outcome set (COS) for maternal and neonatal health research and surveillance during emerging and ongoing epidemic threats and to agree on outcomes' definitions.

Methods: We conducted a systematic review of observational and experimental studies related to epidemics to identify outcomes, and a four-stage modified-Delphi consensus. 150 international stakeholders participated in online surveys, and 24 representatives in consensus meetings. The panels were diverse, with balanced representation of professional background, gender, and geography, including civil society representatives. Outcome were included if ≥ 80% of participants scored them as critically important and ≤10% rated them as not important.

Findings: The final COS includes seven main maternal outcomes-pregnancy outcome, maternal death, suspected symptomatic infection, confirmed infection, severe disease, preterm delivery, mode of birth; seven complementary maternal outcomes-antepartum haemorrhage, postpartum haemorrhage, hypertensive disorders of pregnancy, maternal sepsis, admission to intensive care unit/special units, respiratory support, depression and anxiety; 11 main neonatal outcomes-neonatal death, neonatal suspected symptomatic infection, confirmed infection, severe disease, vertical transmission, low birth weight, prematurity, congenital disorder, respiratory support, skin-to-skin contact, breastfeeding; and, four complementary neonatal outcomes-admission to neonatal intensive care unit/special units, respiratory failure, birth asphyxia, sepsis.

Interpretation: This COS could contribute to standardize maternal and neonatal outcomes selection and reporting in observational and experimental studies, facilitating efficient data comparison and timely evidence-based decision-making in the context of ongoing and emerging epidemic threats.

Funding: Bill & Melinda Gates Foundation (grant INV-041181) and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (HQHRP2422779).

Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence, yet there are few well-designed oral HPV epidemiology studies in general populations. This study assessed oral HPV prevalence and risk-factors among a general population in Europe and the United States (US).

Methods: The cross-sectional study was conducted between November 2020 and July 2023 in 105 dental offices in France, Germany, Spain, the United Kingdom (UK) and US. Participants were aged 18-60 and visiting dental clinics for routine examination. Participants provided oral gargle specimen for HPV DNA and genotyping and completed behavioral questionnaires. HPV DNA detection and genotyping was performed using SPF10/DEIA/LiPA25 at central laboratories.

Findings: Of 7674 participants, mean (SD) age was 40.0 (11.9), and 45.8% were males. Among men, any oral HPV prevalence ranged between countries from 6.6% to 15.0% and 1.8%-4.5% for high-risk (HR) types. Among women, any oral HPV prevalence ranged between countries from 3.6% to 6.8% and 0.2%-2.1% for HR types. HR infection among men was associated with older age (AOR 1.04; 95% CI: 1.02, 1.06); marijuana use (AOR 1.92; 95% CI: 1.19-3.11); increasing number of lifetime female oral sex partners; and by country, residing in the UK compared to Spain (AOR 2.89; 95% CI: 1.30-6.43). HR infection among women was associated with lifetime marijuana use (AOR 2.33; 95% CI: 1.18-4.60) and by country, residing in France compared to Spain (AOR 4.46; 95% CI: 1.26-15.77).

Interpretation: Oral HPV burden was highest among older men who may be at risk of developing OPSCC.

Funding: Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Background: The Middle East and North Africa (MENA) region is the most affected by hepatitis C virus (HCV) infection globally. This study aimed to estimate HCV incidence among people who inject drugs (PWID) in MENA and evaluate the impact of interventions.

Methods: A mathematical model was extended and applied to 13 countries with at least one data point on the population size of PWID and HCV antibody prevalence among PWID, generating estimates for the period 2024-2030. The model was calibrated using multiple datasets, primarily derived from systematic reviews and meta-analyses. Multivariable uncertainty analyses were conducted.

Findings: Incidence rate among PWID in the 13 countries combined was 10.4 per 100 person-years (95% UI: 8.0-14.1), with an estimated 42,364 new infections annually (95% UI: 27,990-57,540), accounting for 16.9% (95% UI: 8.3-28.2) of all cases in these countries. These figures varied widely across countries. A 75% reduction in needle/syringe sharing decreased viremic chronic infection prevalence by 14.2% (95% UI: 11.3-17.1), incidence rate by 33.8% (95% UI: 30.2-40.5), and annual new infections by 24.4% (95% UI: 17.7-30.1). A 10% reduction in PWID numbers and a 20% reduction in injection frequency decreased chronic infection prevalence by 1.7% (95% UI: 1.4-2.5), incidence rate by 4.2% (95% UI: 3.9-4.4), and annual new infections by 11.1% (95% UI: 10.9-11.9). Achieving 75% direct-acting antiviral treatment coverage by 2030 decreased chronic infection prevalence by 65.3% (95% UI: 64.8-65.8), incidence rate by 34.5% (95% UI: 29.6-40.3), and annual new infections by 25.3% (95% UI: 19.9-29.3). Combinations of interventions reduced these epidemiologic outcomes by up to 80%.

Interpretation: MENA experiences considerable HCV incidence among PWID. While the interventions showed potential, only large-scale or multi-intervention strategies can achieve meaningful reductions in HCV transmission.

Funding: This publication was made possible by NPRP grant number 12S-0216-190,094 from the Qatar National Research Fund (a member of Qatar Foundation). The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions, or policies of World Health Organization.

Prenatal and intrapartum invasive tests are possible mechanisms of mother to child transmission (MTCT) of hepatitis B virus (HBV). The viral activity can affect the MTCT risk after invasive tests, but the evidence is scarce. This scoping review discussed the effects of prenatal or intrapartum invasive tests on the risk of HBV MTCT. The risk of MTCT after amniocentesis was low among hepatitis B infected pregnant individuals with negative hepatitis B e antigen (HBeAg) statuses or HBV DNA < 7 log₁₀ IU/mL, and comparable to those that did not undergo prenatal invasive tests. Amniocentesis could increase the risk of MTCT among women with seropositive HBeAg statuses or HBV DNA ≥ 7 log₁₀ IU/mL, but there were no MTCT among these women who received antiviral treatment. Data on CVS, cordocentesis and intrapartum invasive tests were insufficient to conclude their effects on MTCT. We also reviewed 50 international clinical practice guidelines. Most of them did not have recommendations on the management of hepatitis B infected pregnant individuals requiring prenatal or intrapartum invasive tests and significant discrepancies existed among the remaining guidelines. A workflow and two pragmatic approaches were discussed to assist clinical management. Furthermore, we would like to encourage future research to provide comprehensive data on the factors influencing the MTCT rate (such as maternal HBV DNA viral load and HBeAg status, availability and timing of neonatal birth dose immunizations, transplacental or transamniotic invasive tests, complications of the invasive tests and the use of antiviral prophylaxis).

Progress towards achieving global elimination of hepatitis B virus (HBV) by 2030 remains unsatisfactory. Prevention of mother to child transmission is crucial but current Clinical Practice Guidelines (CPGs) gave diverse recommendations, creating confusion and leading to significant challenges in the practical implementation across various regions owing to global inequity. We reviewed 47 CPGs on the management of hepatitis B during pregnancy against twelve important clinical questions. Of 47 guidelines, 80.9% (38/47) supported the universal approach to HBV screening. To select women for antiviral prophylaxis, 78.7% (37/47) recommended the use of HBV DNA levels, while 31.9% (15/47) recommended the use of HBeAg. Of 37 guidelines recommending HBV DNA levels, 94.6% (35/37) recommended a viral load threshold of >200,000 IU/mL to initiate antiviral prophylaxis. Of 16 guidelines addressing the mode of delivery, 87.5% (14/16) encouraged vaginal birth. Of 30 guidelines addressing breastfeeding, 60% (18/30) recommended breastfeeding. However, controversies were found in the optimal timing of HBV disease evaluation during pregnancy and the ideal timing to stop antiviral prophylaxis after delivery. Of 36 guidelines addressing the timing to initiate antiviral prophylaxis, 25% (9/36) advised starting prophylaxis between 24 and 28 weeks, while 75% (27/36) suggested other timings or provided vague descriptions. Of 38 guidelines addressing birth-dose vaccination, 42% (16/38) emphasized the importance of "vaccination as soon as possible after birth." These deficiencies and discrepancies among CPGs could significantly impede global HBV elimination.

Background: Heart Failure (HF) quality of care (QoC) is associated with clinical outcomes. Therefore, we investigated differences in HF QoC across worldwide regions (with differing national income) and the association of quality indicators with outcomes.

Methods: We examined the quality of care (QoC) in acute heart failure (HF) patients across different regions using quality indicators (QIs) from the European Society of Cardiology (ESC) and the American Heart Association (AHA) to evaluate QoC. The analysis included 17,632 patients enrolled from 358 medical centres in 44 countries between 23 July 2014 and 24 March 2017, all part of the prospective REPORT-HF cohort study. We investigated how QoC varied by region and its relationship with mortality rates at 30 days and 1 year after hospital discharge. For each QI, percentage attainment of QI among eligible patients was calculated and compared across regions.

Findings: Among 17,632 patients (median age: 67 years; 61% women) followed up for a median of two years, we assessed 16 QIs. QIs that were least often achieved included measurement of natriuretic peptides, performance of echocardiography, treatment with guideline medical therapy, and a scheduled follow-up consultation after discharge. QI achievement was significantly lower in lower-than higher-income countries. Higher (≥50% vs. <50%) achievement of cumulative QIs was associated with lower 30-day (hazard ratio [HR] 0.58, 95% Confidence Interval [CI] 0.40-0.83; p < 0.001), and 1-year mortality (HR 0.58, 95% CI 0.50-0.68; p < 0.001).

Interpretation: QoC is lower in lower-than higher-income countries and lower QoC is associated with worse outcomes. Improving QoC by addressing structural barriers and quality improvement programs may improve the outcomes of patients with HF.

Funding: Novartis.

Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete. The international consensus-based CONSORT-DEFINE (Consolidated Standards for Reporting Trials Dose-finding Extension) statement, an extension of the CONSORT statement for randomised trials, was developed to improve the reporting of EPDF trials. The CONSORT-DEFINE statement introduced 21 new items and modified 19 existing CONSORT items.This CONSORT-DEFINE Explanation and Elaboration (E&E) document provides important information to enhance understanding and facilitate the implementation of the CONSORT-DEFINE checklist. For each new or modified checklist item, we provide a detailed description and its rationale with supporting evidence, and present examples from EPDF trial reports published in peer-reviewed scientific journals. When reporting the results of EPDF trials, authors are encouraged to consult the CONSORT-DEFINE E&E document, together with the CONSORT and CONSORT-DEFINE statement papers, and adhere to their recommendations. Widespread adoption of the CONSORT-DEFINE statement is likely to enhance the reporting quality of EPDF trials, thus facilitating the peer review of such studies and their appraisal by researchers, regulators, ethics committee members, and funders.

Funding: This work is a further extension of the CONSORT-DEFINE study, which was funded by the UK Medical Research Council (MRC)-National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1). The Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec 22/100 004), which has contributed to accelerating the advancement and successful completion of this work.

Background: Suicide is a leading cause of death for young people. Half of young adult suicides are by firearm, and many involve alcohol consumption. We aimed to assess the impact of the minimum legal drinking age (MLDA) of 21 years on rates of alcohol positive firearm and non-firearm suicide.

Methods: We used a regression discontinuity approach with data from the National Violent Death Reporting System (NVDRS) 2005-2021, among U.S suicide decedents in 14 states aged 16-35 years. The primary outcomes were the change in the proportion of tests positive for alcohol and the change in rates of alcohol positive suicide per 100,000 population at the MLDA.

Findings: Across 14 states and 169 state-years, there were 434 alcohol positive suicides at age 20 and 684 alcohol positive suicides at age 21. The percentage of suicides with a positive alcohol test increased from 29.5% at age 20 to 38.7% at age 21 (p < 0.001), with a larger increase among firearm suicides relative to non-firearm suicides. Accounting for age-related trends, the total alcohol positive suicide rate increased by 1.52 per 100,000 (p < 0.001) at the MLDA, mostly due to an increase in alcohol positive firearm suicide. Compared to the expected rate in the absence of the MLDA, there was a 47.5% (95% CI 24.1%-81.8%) excess in firearm suicides, equivalent to 137 (95% CI 82-191) excess deaths. There was no discontinuity in the rate of alcohol negative firearm suicides at age 21. Blood alcohol content was not affected by the MLDA but was higher for firearm suicides across all ages.

Interpretation: There was a large increase in the rate of alcohol positive suicide at the minimum legal drinking age (MLDA), driven by firearm suicide. Policies and programmes should aim to weaken the link between alcohol and firearms among those at or just above legal drinking age to prevent suicide.

Funding: The Commonwealth Fund and The Joyce Foundation.