PLoS Medicine最新文献

Background: Major fetal anomalies are an important cause of perinatal morbidity and mortality. While routine second-trimester ultrasound screening around 20 weeks is the current standard, advances in imaging have enabled earlier anatomical assessment in the first trimester. Despite increasing practice of early screening in England, there is no national policy recommending first-trimester anatomical evaluation, and little is known about its impact on detection rates at population level. Our aim was to examine if different policies of fetal anatomical ultrasound practice have an impact on earlier diagnosis of major fetal anomalies.

Methods and findings: We conducted a nationwide, population-based study linking data from a national survey of first-trimester ultrasound protocols in all NHS maternity units in England with congenital anomaly registration data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) for pregnancies between April 2017 and March 2019. NHS trusts were classified into four protocol groups: no anatomical assessment, basic, advanced, and extended anatomical protocols. We evaluated the proportion of 14 predefined major congenital anomalies detected prior to 16 weeks' gestation across these groups. A total of 1,030,224 pregnancies were included from 110 NHS trusts (84% response rate), with 5,895 fetuses affected by one of the anomalies of interest. First-trimester anatomical assessment was routinely conducted in 75% of trusts, though the scope varied. Overall, 32.7% (95% CI 31.5-33.9) of anomalies were detected before 16 weeks, with detection rates increasing stepwise by protocol detail: 27.7% (95% CI 25.4-30.0) in trusts with no protocol to 40.4% (95% CI 37.3-43.4) in those with extended protocols (p < 0.0001 for trend). Conditions such as acrania, exomphalos, and gastroschisis were commonly detected early regardless of protocol, whereas for anomalies such as spina bifida, limb reduction defects, and major cardiac malformations, detection was significantly higher in centers employing detailed first-trimester anatomical protocols. Due to data access restrictions and confidentiality considerations, analyses were conducted at the level of protocol group rather than individual hospitals. Hospital-level characteristics, including sonographer expertise and patient population risk, could not be adjusted for and may act as confounders.

Conclusions: More detailed first-trimester anatomical screening protocols are associated with significantly higher early detection rates of major fetal anomalies. While current practices vary considerably across England, this study provides population-level evidence suggesting that systematic first-trimester screening could improve the timeliness of anomaly detection. These findings support the consideration of standardized national guidance to reduce inequity and enhance prenatal care.

Just as tuberculosis services were recovering after the COVID-19 pandemic disruptions, abrupt funding cuts by G7 nations are putting progress at risk. These trends, while perilous, also reveal a turning point toward a more equitable, resilient, and self-reliant TB response, led by high-burden countries.

Background: There is growing evidence that access to joint replacement surgery is being restricted based on body mass index (BMI) despite any formal recommendations. Our aim was to investigate the association between BMI and patient outcomes after elective primary shoulder replacement surgery to inform future commissioning and national guidance.

Methods and findings: In this population-based cohort study, patients aged 18-100 years having elective primary shoulder replacement surgery were identified using linked national joint registry and hospital data from public and private hospitals in the United Kingdom (2018-22) and Denmark (2006-21). The main outcome measure was mortality within 365 days of surgery. Secondary outcome measures included mortality within 90 days, serious adverse events within 90 days, and revision surgery within 4.5 years of surgery. The association between BMI and patient outcomes was assessed using flexible parametric survival models and logistic regression models, adjusting for age, sex, deprivation, main surgical indication and American Society of Anaesthesiologists (ASA) score. 15,320 and 5,446 shoulder replacement procedures from within the United Kingdom and Denmark, respectively, met the inclusion criteria. In the United Kingdom, the average age was 72.2 years, 68.3% were female and the average BMI was 29.4 kg/m2. In Denmark, the average age was 70.5 years, 65.3% were female and the average BMI was 28.0 kg/m2. There was a decreased risk of 365-day mortality in obese (BMI 40 kg/m2) patients (hazard ratio (HR) 0.40 [95%CI 0.21, 0.73]) and an increased risk in underweight (BMI < 18.5 kg/m2) patients (HR 1.18 [95%CI 1.06, 1.32]), compared to patients with BMI 21.75 kg/m2. Underweight patients had an increased risk of 90-day mortality (HR 1.69 [95%CI 1.14, 2.52]), 90-day serious adverse events (odds ratio 1.36 [95%CI 1.05, 1.77]) and revision surgery (HR 1.70 [95%CI 1.25, 2.33]). Increasing BMI was not associated with a significantly increased risk of any secondary outcome. The main limitation of this study was the high proportion of missing BMI data and the small case numbers for the underweight study population (n = 131[UK], 70[Denmark]).

Conclusions: Increasing BMI was associated with lower 365-day mortality, and no poorer outcomes after elective primary shoulder replacement surgery. This surgery is safe and effective in obese patients and access to shoulder replacements should not be restricted based on BMI alone. Clinicians and hospitals should be aware that underweight patients appear more at risk of mortality, serious adverse events and revision surgery after shoulder replacement.

Background: Assisted dying and euthanasia (ADE) for patients with psychiatric disorders or dementia have increased in jurisdictions where the practice is legal. In this study, we examine trends in euthanasia cases involving patients with these conditions in Belgium, where the law makes a distinction based on whether a patient's death is not expected in the foreseeable future (>12 months)-a common situation in cases of dementia or psychiatric disorders.

Methods and findings: We use data on all cases of euthanasia reported to the Federal Commission for the Control and Evaluation of Euthanasia from 2002 (when the legislation was introduced) to 2023 (N = 33,592). Psychiatric disorders and dementia represent 1.27% and 0.92% of all cases, respectively. Using time-series zero-inflated negative binomial regression, we model trends by first examining interactions between euthanasia reasons and year, then extending to three-way interactions with patients' characteristics. The model calculates change in count and is replicated with an offset to account for demographic changes and generate rates. Our results show that euthanasia for psychiatric disorders and dementia showed distinct trends over time. Although slightly increasing, euthanasia for psychiatric disorders followed trends similar to the other types of euthanasia (count = 1.00 [95%CI: 0.98; 1.03]-rate = 1.02 [95%CI: 0.99; 1.04]), while euthanasia cases for dementia increased faster than other types of euthanasia (count = 1.03 [95%CI: 1.00; 1.06]-rate = 1.04 [95%CI: 1.01;1.07]). Trends in euthanasia for dementia and psychiatric disorders coincide with demographic changes. While euthanasia rates for psychiatric disorders were initially higher among women, the rate among men has been increasing over time. Regional trends show higher overall euthanasia rates in the Dutch-speaking population, but with faster increases in the French-speaking population. A key limitation of this study is the lack of information on patients' socio-economic profiles.

Conclusions: In Belgium, between 2002 and 2023, there are distinct trends for euthanasia for non-terminal illnesses. Euthanasia for psychiatric disorders followed similar trends as euthanasia for terminal illnesses, whereas euthanasia cases involving cognitive conditions increased at a faster rate. Furthermore, there were gender and regional differences, which diminished over time.

Background: Uncertainties persist regarding the precise shape of the smoking-outcome curves across various cardiovascular and mortality endpoints. This study aims to elucidate the relationships among smoking burden, intensity, and cessation duration across multiple cardiovascular outcomes.

Methods and findings: Cox proportional hazard models were constructed to evaluate the association between pack-years, cigarettes per day (CPD), and years since cessation with cardiovascular outcomes in participants from 22 prospective cohort studies within the Cross-Cohort Collaboration Tobacco Working Group. We evaluated myocardial infarction (MI), stroke, coronary heart disease (CHD; MI, coronary revascularization, or coronary death), cardiovascular disease (CVD; stroke or cardiovascular death), heart failure (HF), atrial fibrillation (AFib), CHD mortality, CVD mortality, and all-cause mortality. Median follow-up varied across outcomes, with 14.4 years for MI (17,570 events), 19.3 years for CHD (30,625 events), 18.6 years for CVD (54,078 events), and approximately 19.4-19.9 years for mortality outcomes (CHD mortality: 17,429 events; CVD mortality: 33,120 events; all-cause mortality: 125,044 events). Spline terms were used to investigate the nonlinear association of continuous smoking/cessation measures with the examined outcomes. Models were adjusted for demographic, socioeconomic, and other cardiovascular risk factors. The study included 323,826 adults (148,635 non-mortality and 176,396 mortality outcomes with 25 and 16 million person-years at risk, respectively). Compared to never-smokers, current smokers had significantly increased risks for CVD (hazard ratio (HR) 1.74, 95% confidence intervals (CIs) [1.66,1.83] in men; HR 2.07, 95% CI [2.00,2.14] in women) and all-cause mortality (HR 2.17, 95% CI [2.09,2.25] in men; HR 2.43, 95% CI [2.38,2.48] in women; all p < 0.001). Compared with never-smokers, participants with 2-5 CPD demonstrated substantially elevated cardiovascular risks, with HR ranging from 1.26 (95% CI [1.09,1.45], p = 0.002) for AFib to 1.57 (95% CI [1.39,1.78], p < 0.001) for HF. Smoking 2-5 CPD was associated with increased CVD mortality (HR 1.57, 95% CI [1.41,1.75]), and all-cause mortality (HR 1.60, 95% CI [1.52,1.69]; both p < 0.001). Smoking 11-15 CPD conferred a higher risk of CVD (HR 1.87, 95% CI [1.69,2.06]) and all-cause mortality (HR 2.30, 95% CI [2.14,2.47]; both p < 0.001). The increased risk associated with the evaluated outcomes was steeper for the initial 20 pack-years and 20 CPD, respectively, compared to further smoking exposure. The most substantial reduction in risk across all outcomes was observed within the first 10 years after smoking cessation. However, the progressive risk reduction continues over extended time periods, with former smokers demonstrating over 80% lower relative risk than those of current smokers within 20 years of cessation. Limitations include potential exposu

Introduction: In 2023, almost 200,000 children under 15 years died from tuberculosis, most without appropriate treatment. Treatment decision algorithms (TDAs), developed to facilitate rapid anti-tuberculosis treatment initiation in children, were recommended by the World Health Organization (WHO) in 2022, conditional on validation in different cohorts and settings. We performed a retrospective external evaluation of WHO TDAs using an individual participant dataset (IPD).

Methods and findings: The IPD comprised four paediatric cohorts, restricted to children with presumptive pulmonary TB < 10 years, and including children in high-risk groups (children living with HIV "CLHIV", children with severe acute malnutrition "SAM", and children <2 years). All children in the IPD were retrospectively evaluated using both TDA A (an algorithm including chest X-ray) and TDA B (without chest X-ray), excluding the triage step. The diagnostic accuracy against a composite reference standard (confirmed and unconfirmed tuberculosis versus unlikely tuberculosis) was determined and reported as sensitivities and specificities. Of 1,886 children included (RaPaed-TB: n = 740, Umoya: n = 474, TB-Speed HIV: n = 204, TB-Speed Decentralisation: n = 468), the median age was 2.9 years (interquartile range [IQR]:1.3,5.5), 741 (39.3%) were <2 years, 382 (20.3%) were CLHIV, and 284 (15.1%) had SAM. 281 (14.9%) had confirmed tuberculosis, 672 (35.6%) were classified as unconfirmed tuberculosis (clinically diagnosed, microbiological investigations negative), and 933 (49.5%) as unlikely tuberculosis. For TDAs A and B, algorithm sensitivity was 84.3% (95% CI: 74.8, 90.6) and 90.6% (95% CI: 83.8, 94.7), respectively, with a specificity of 50.6% (95% CI: 30.4, 70.7) and 30.8% (95% CI: 21.5, 42.0), respectively. For TDA A, estimated sensitivity in children in high-risk groups was lower than those with low-risk (83.0%, 95% CI: 79.4%, 86.1%; versus 88.0%, 95% CI: 84.8%, 90.6%), while having a gain in specificity (50.0%, 95% CI: 44.9%, 55.1%; versus 36.6%, 95% CI: 32.7%, 40.7%). Trends were similar for TDA B. As for limitations, most diagnostic tuberculosis studies in children, including two of those included in the IPD, are performed at secondary or tertiary hospitals with higher levels of healthcare and thus the target population might differ somewhat from the IPD, potentially limiting the generalisability of our results.

Conclusions: This retrospective external evaluation of WHO TDAs in a large IPD shows high sensitivity but sub-optimal specificity for both TDAs, in line with the meta-analyses that generated the algorithms. Prospective studies that evaluate the entire TDA, including triage step are needed. Additionally, the integration of novel diagnostic tools within the TDAs should aim to enhance the accuracy, especially the specificity.

Recent research has examined factors contributing to the successful transition of middle-income countries away from international health aid. Three factors are especially important: effective leadership, using domestic resources to close the financing gap created by loss of aid, and realigning country systems to new sources of domestic funding.

Background: Evidence on the diagnostic yield of genome-wide non-invasive prenatal testing (GW-NIPT) is growing, but its comparative clinical and economic impact as a first-tier screening strategy for fetal chromosomal abnormalities remains unassessed. We compared GW-NIPT with targeted NIPT and first-trimester combined testing (FCT), in a Dutch setting where all pregnancies also undergo a routine second-trimester anomaly ultrasound scan (scan), to guide policymakers on optimal prenatal screening approaches.

Methods and findings: We developed a decision-analytic model for a cohort of 175,000 pregnancies, reflecting the Dutch obstetric population. All strategies screened for common trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome); GW-NIPT additionally considered rare autosomal trisomies and structural aberrations. Model inputs were based on the TRIDENT-2 study data and historical FCT data. Base-case unit costs were €166 (scan), €191 (FCT), and €350 (NIPT). Sensitivity analyses were conducted to account for uncertainties in model parameters and potential country-specific variations. Outcomes included total screening costs, number of fetal chromosomal abnormalities diagnosed, number of invasive procedures, and expected procedure-related euploid fetal losses. We summarized economic results as cost per diagnosed case and incremental cost per additional diagnosis across strategies. GW-NIPT yielded the highest number of diagnoses (545) versus targeted NIPT (514) and FCT (452), and the lowest cost per diagnosed case (€152,785), compared with targeted NIPT (€159,852) and FCT (€170,050). Invasive tests required per diagnosis were lower for GW-NIPT and targeted NIPT (both 6) than for FCT (13), implying a lower risk of procedure-related miscarriage (iatrogenic miscarriage). Sensitivity analyses indicated that test uptake and unit costs strongly influenced outcomes. GW-NIPT remained the most favorable in terms of cost per diagnosis for NIPT prices up to €467. Key limitations include the use of a decision-analytic model without quality-of-life outcomes and the lack of comparisons against explicit cost-effectiveness thresholds. Therefore, the results should be interpreted as relative clinical and economic comparisons rather than cost-effectiveness judgements.

Conclusions: Among the strategies evaluated, first-tier GW-NIPT had the greatest diagnostic yield and the lowest cost per diagnosis, improving detection rates and supporting reproductive autonomy at lower costs. Implementation decisions should also consider local pricing, laboratory capacity, and counseling resources. Future research that links screening outcomes to long-term health consequences (e.g., quality-adjusted life years or life-years), healthcare utilization, costs, and psychosocial outcomes will enable formal cost-effectiveness evaluations and support further refinement of prenatal screening policy.

Background: Poverty alleviation is a major global development goal. Vaccines have the potential to provide financial risk protection (FRP) by preventing illnesses and associated healthcare costs. We estimate the lifetime FRP benefits generated by major vaccines among individuals vaccinated between 2000 and 2030 in low- and middle-income countries (LMICs).

Methods and findings: We developed a microsimulation model to quantify the number of cases of catastrophic health expenditure (CHE) averted by a range of vaccines in 52 Gavi-eligible countries, stratified by wealth quintile. Vaccines protecting against five pathogens were considered, i.e., hepatitis B (routine and birth dose vaccine), Haemophilus influenzae type B, rotavirus, measles (routine and supplementary campaign vaccine), and Streptococcus pneumoniae. Model inputs were obtained from secondary data sources, including infection reduction rates under various immunization coverage scenarios, out-of-pocket health expenditures, transportation costs, wage losses, and healthcare utilization associated with disease treatment and consumption expenditures. CHE cases were defined as exceeding 10% of annual consumption, with sensitivity analyses conducted using thresholds of 25% and 40%, as well as impoverishing health expenditures were estimated. All vaccines, singly and collectively, showed a large impact on FRP and could avert ~200 million CHE cases across 52 Gavi-eligible countries from 2000 to 2030. Importantly, about half of all CHE cases were prevented among the poorest quintiles. When evaluated at a 10% threshold for CHE, the first dose of measles vaccine stood out in averting around 1,400 CHE cases per 10,000 vaccinated individuals in the poorest quintile, that is a total of 44 million CHE cases averted. A key limitation is the assumption of uniform disease risks in the absence of vaccination across quintiles, which may underestimate benefits for poorer groups.

Conclusions: Vaccines can provide substantial FRP benefits, particularly among the most disadvantaged populations. Sustained investments to ensure vulnerable populations receive vaccinations in LMICs can therefore not only improve health outcomes but also contribute to poverty reduction.