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Background: Epileptic seizures during pregnancy may increase the risk of adverse pregnancy outcomes. Socioeconomic disparities in epilepsy incidence may extend to seizure control. We conducted a systematic review and meta-analysis to assess the association between epileptic seizures during pregnancy and adverse pregnancy outcomes. We also evaluated the association between socioeconomic and individual-level factors and seizure occurrence.

Methods and findings: We searched MEDLINE, Embase, CINAHL, and PsycINFO databases from inception to May 2025 for observational studies on pregnant women with epileptic seizures. We compared maternal and foetal outcomes in pregnant women with and without seizures and assessed the association between seizure occurrence and socioeconomic or individual-level factors. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies. Meta-analyses using random effects model were performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). From 13,381 identified publications, 25 studies (24,596 pregnancies) are included in this analysis. In pregnant women with epilepsy, women with seizures compared to those without had increased odds of caesarean birth (OR 1.62, 95% CI 1.14 to 2.30, p = 0.007), peripartum depression (OR 2.20, 95% CI 1.04 to 4.65, p = 0.04), and small for gestational age baby (OR 1.32, 95% CI 1.03 to 1.69, p = 0.03). The odds of preterm birth (OR 1.66, 95% CI 1.29 to 2.15, p < 0.001), low birthweight (OR 1.47, 95% CI 1.12 to 1.93, p = 0.006), and small for gestational age baby (OR 1.44, 95% CI 1.19 to 1.74, p < 0.001) were higher in women with seizures compared to women without epilepsy. The risk of seizures was greater in pregnant women with epilepsy with low income compared to those with higher income (OR 1.57, 95% CI 1.22 to 2.02, p < 0.001), and in women with focal epilepsy compared to those with generalised epilepsy (OR 1.84, 95% CI 1.54 to 2.20, p < 0.001). The number of studies for some outcomes was small, limiting subgroup analyses and detection of heterogeneity.

Conclusion: Epileptic seizures are associated with increased risks of adverse maternal and foetal outcomes. Risk assessment to identify women with epilepsy at highest risk of seizures is needed to optimise care.

The TARGET guidelines aim to improve transparency and consistency in reporting of observational studies that emulate target trials. In alignment with these goals, PLOS Medicine fully endorses the TARGET guidelines and now asks that new submissions of target trial emulation studies adhere to them.

A recent PLOS Medicine study shows that atrial fibrillation lowers the specificity of the biomarker NT-proBNP for heart failure. Adjusted thresholds and better echocardiography access are therefore required for NT-proBNP to remain as a high negative predictive value rule-out test in primary care.

Background: N-terminal pro-B-type natriuretic peptides (NT-proBNP) are important in the assessment of suspected heart failure (HF). However, NT-proBNP concentrations are elevated in atrial fibrillation (AF), creating diagnostic uncertainty. The aim of this study was to assess the diagnostic accuracy of NT-proBNP for HF in people with AF, overall and by age, sex and BMI.

Methods and findings: Retrospective study of all patients with a NT-proBNP test in their primary care electronic health record among English GP practices provided through the Clinical Practice Research Datalink (2004-2018) and linked to secondary care data. The accuracy of NT-proBNP for diagnosing HF within six months was assessed for people with and without AF at thresholds of 125, 400, 660 and 2,000 pg/mL, including by age, sex and BMI. Among 155,347 people who had an NT-proBNP test organized in primary care (median age 61 years), 17,403 (11.2%) had pre-existing AF. Of the 155,347 people included, 14,585 (9.4%) were subsequently diagnosed with HF, including 4,168/17,403 (23.9%) people with AF (median NT-proBNP = 1,852 pg/mL, interquartile range (IQR) [974, 3,459] pg/mL) and 10,417/137,944 (7.6%) without AF (1,110 pg/mL, IQR [434, 3,108] pg/mL). NT-proBNP discriminated better overall among people without AF (AUC = 0.877 (95% confidence interval (CI) [0.873, 0.881]) than with AF (AUC = 0.743 (95% CI [0.735, 0.751]). Among people with AF, NT-proBNP sensitivity and specificity at a 125 pg/mL threshold was 98.8% (95% CI [98.5%, 99.1]) and 13.2% (95% CI [12.6%, 13.7]) and at 400 pg/mL 93.2% (95% CI [92.4, 93.9]) and 35.5% (95% CI [34.7, 36.3]). Among people without AF the corresponding results were 92.9% (95% CI [92.4, 93.4]) and 53.8% (95% CI [53.6, 54.1]) at 125 pg/mL and 77.1% (95% CI [76.3, 77.9]) and 84.9% (95% CI [84.7, 85.1]) at 400 pg/mL. NT-proBNP discriminated less well among people with AF aged ≥65 years compared to <65years (e.g., AUC in people aged 65-75 years was 0.725, 95% CI [0.712, 0.739]). Increasing the threshold for a positive test among people with AF from 125 pg/mL to 660 pg/mL would reduce the number of false positive results by 26.0%, whilst retaining a negative predictive value of 91.5 (95% CI [90.8, 92.1]), albeit with a 10.6% increase in the proportion of those tested with AF having a missed or delayed HF diagnosis. The main limitation of the study is that it relies on routinely collected primary care data and people with an NT-proBNP result <400 pg/mL may not have been referred for further assessment, impacting upon the diagnostic accuracy below this threshold.

Conclusions: NT-proBNP discriminates more accurately for HF among people without AF than with AF. A higher referral threshold could be considered in AF to account for higher median NT-proBNP levels but this would also increase missed HF diagnoses.

[This corrects the article DOI: 10.1371/journal.pmed.1004631.].

Background: Although opioids are usually not recommended for young people they are often prescribed. It is not clear whether family-level factors are related to the risk of opioid use among adolescents and young adults. The aim of this study is to examine the association between parental opioid prescriptions and risk of opioid use in young people.

Methods and findings: A prospective cohort study, including 21,470 adolescents and young adults (13-29 years) participating in the third (2006-2008) or fourth (2017-2019) survey of the population-based Young-HUNT or HUNT Study, Norway, paired with at least one participating parent. Opioid prescriptions were obtained by a linkage to the Norwegian Prescription Database. Parents' opioid prescriptions were defined as '0', '1', and '≥2' prescriptions over a period of 5 years. Analyses were also stratified according to parental chronic musculoskeletal (MSK) pain status (no, yes) assessed by the Standardised Nordic Questionnaire. Two outcomes were assessed: 1) any opioid prescription, and 2) persistent opioid prescriptions (i.e., at least three out of four quarters of the year). Analyses were adjusted for parental age, parental education level, parental body mass index, offspring age, and offspring participation survey. Follow-up started at the date of survey participation and ended at the date of prescription, emigration/death, or 7-year follow-up. If the mother or father had ≥2 opioid prescriptions, the hazard ratios (HR) for persistent opioid prescriptions in offspring were 2.60 (95% CI [1.86, 3.65]) and 2.37 (95% CI [1.56, 3.60]), respectively, compared to offspring whose parents did not receive any opioid prescriptions. There was no clear evidence that parental chronic MSK pain status influenced these associations. Comparing offspring of mothers with ≥2 versus no opioid prescriptions, the HR for any opioid prescription was 1.30 (95% CI [1.15, 1.47]) if the mother reported chronic MSK pain and 1.31 (95% CI [1.06, 1.62]) if she did not. Corresponding HRs associated with fathers' opioid prescription were 1.19 (95% CI [1.01, 1.41]) if the father reported chronic MSK pain and 1.21 (95% CI [0.98, 1.50]) if he did not. Residual confounding due to unmeasured factors cannot be excluded.

Conclusions: Parental opioid prescription is related to an increased risk for opioid initiation and persistent use in offspring, irrespective of parental history of chronic MSK pain. These findings suggest that family-based strategies should be considered when managing pain and opioid use in young people.

Background: The World Health Organization (WHO) launched the Acceleration Plan to STOP Obesity, highlighting the urgent need for timely implementation of proven interventions. Fiscal policies, including taxes on sugar-sweetened beverages (SSB) and non-essential energy-dense foods (NEDF), are among the most cost-effective strategies to reduce obesity rates. Delays in adopting or strengthening these measures can undermine their impact, and the consequences of postponing such policies remain unmeasured. We aimed to estimate the expected impact of delaying doubling the SSB and NEDF tax in Mexico.

Methods and findings: We simulated a closed cohort of Mexican adults aged 20 years and over from 2021 to 2040. The simulated sample corresponded to the combination of the 2020-22 Health and Nutrition Surveys, which contained anthropometric and demographic information representative at a national level. We projected annual average Body Mass Index (BMI), obesity prevalence, deaths averted, and years lived without obesity (YLWO) under four scenarios: status quo and doubling the current tax on SSB and NEDF in 2025, 2030, and 2035. BMI was projected from 2021 to 2040 using Hall's microsimulation weight change model, and a Mexican projection of total energy intake. To simulate deaths, we estimated the probability of all-cause mortality by BMI category from the National Population Council projections of the Mexican population by age and year. By 2040, doubling the taxes in 2025 resulted in an obesity prevalence of 41.6% (95% Uncertainty Interval [40.2,43.1]) in contrast to the status quo scenario (44.5%, 95% Uncertainty Interval [43.2,45.8]), and 170,600 deaths averted (95% Uncertainty Interval [130,900, 210,200]) and 25,031,900 (95% Uncertainty Interval [19,048,500, 31,015,300]) YLWO gained. A delayed intervention in 2035 resulted in an obesity prevalence of 41.7% (95% Uncertainty Interval [40.4,43.1]), 38,900 deaths averted (95% Uncertainty Interval [29,600, 48,200]), and 4,473,700 (95% Uncertainty Interval [3,378,900, 5,568,500]) YLWO gained. Our results apply only to individuals aged 20 years or older in 2021, excluding cohorts reaching age 20 between 2022 and 2040.

Conclusions: Our results emphasize the urgency of advancing WHO's Acceleration Plan to STOP Obesity. Postponing evidence-based interventions is estimated to exacerbate the burden of obesity, mortality, and suffering.