[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.
Background: Social media (SM) platforms have become increasingly prevalent in adolescents' lives, and concerns have arisen regarding their potential contribution to depression. This study examined whether excessive SM use contributes to rising adolescent depression rates and evaluated potential mitigation strategies.
Methods and findings: We developed an individual-based microsimulation model of 18.6 million French adolescents born 1990-2012, tracking depression outcomes from 2000-2022 (analyses conducted August 2024-July 2025). The model incorporated 95 parameters, including demographics, SM use patterns, and established depression risk factors (childhood adversities, chronic physical conditions, physical inactivity, obesity, substance use). The main outcome was cumulative depression cases, and secondary outcomes were suicide deaths, health-adjusted life expectancy (HALE) loss, and associated costs. The model was well-calibrated and validated adequately against US-specific data. It showed that excessive SM use likely played an important role in the recent increase in rates of adolescent depression. Among French adolescents, simulations indicated that excessive SM use was associated with an additional cumulative lifetime 590,000 depression cases (95%CI [400,000, 760,000]), 799 suicide deaths (95%CI [547, 1,028]), 137,000 (95%CI [94,000, 176,000]) HALE loss years, and 3.94 (95%CI [2.70, 5.07]) billion euros, compared to scenarios without SM platforms. Key limitations are that microsimulation modeling cannot establish causality from observational data and the reliance on duration-based exposure measures without capturing content type or engagement quality.
Conclusions: In this study, we estimated that limiting SM use to 1 h per day for all adolescents, replacing 30 min of SM use with 30 min of physical activity, or stopping its use for adolescents most at-risk for depression, would be associated with a reduction in cumulative lifetime prevalence of depression by 14.7%, 12.9%, and 12.0%, respectively, and diminished associated costs. Targeted SM interventions could potentially reduce adolescent depression burden, though real-world implementation and effectiveness require validation.
Emulating a target trial when conducting an observational study of interventions can reduce the likelihood of design-related biases. The TARGET guideline aims to improve the reporting transparency of observational studies emulating a target trial and help readers appraise and apply the results.
Background: Tumor infiltrating lymphocytes (TILs) are prognostic in triple-negative breast cancer, but not estrogen receptor (ER) positive cancers which comprise 70%-80% of breast cancers. This is due to the relatively low immune infiltration in ER-positive tumors. However, few studies have explored the prognostic impact of lower abundance TILs evaluated using spatial methods. The objective of this study was to explore whether the distribution of lymphocytes with respect to tumor cells predicts prognosis.
Methods and findings: In this retrospective cohort study, we used multiplex immunofluorescent (IF)-stained images of tissue microarray cores (stained for cytokeratin [Ck], CD8, and FoxP3) obtained from 1,467 study participants to compute distance-based visual morphometry for epithelial and immune cells, including two new metrics, proximity and consistency. Proximity and consistency are defined as functions of the mean and variance of nearest neighbor distances between Ck+ tumor cells and CD8+ T cells. Prognostic significance of proximity and consistency were compared to lymphocyte counts using log-rank tests of differences in Kaplan-Meier survival curves and Cox proportional hazards models. Better recurrence-free survival (RFS) was observed for both ER+ and ER- breast cancers with high proximity and consistency of CD8+ T cells. Among ER- breast cancers, proximity had the highest RFS hazard ratio (HR 1.84, 95% CI [1.18, 2.87]; p = 0.0069) compared to count and consistency. Among ER-positive participants, RFS hazard ratios for proximity and consistency were 2.04 (95% CI [1.39, 2.98]; p = 0.0003) and 1.82 (95% CI [1.23, 2.69]; p = 0.0026), respectively. These associations were stronger than those observed for lymphocyte count (HR 1.35, 95% CI [0.92, 1.98]; p = 0.1289). Independent prognostic value was demonstrated by controlling clinical and demographic variables such as age, tumor grade, stage, ER status, progesterone receptor status, and human epidermal growth factor receptor 2 status. These IF-derived spatial metrics were also associated with established TILs metrics and RNA expression-based measures of tumor adaptive immune response. Though these results are promising, our exploration of the tumor immune microenvironment was limited by the small number of immune markers available for our data.
Conclusions: Spatial characteristics described by proximity and consistency are frequently associated with recurrence irrespective of ER status. The prognostic significance of proximity in ER+ breast cancer implies that spatial parameters may identify individuals who would benefit from immune therapy; up to 75% of breast cancers experience T cell proximity suggestive of immune susceptibility.
Open science often centers around publications and data transparency. We highlight how and why disseminating results to study participants is essential for maximizing the values and benefits of open science.
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