PLoS Medicine最新文献

{"title":"Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study.","authors":"Yu-Jung Jenny Wei, Almut G Winterstein, Siegfried Schmidt, Roger B Fillingim, Michael J Daniels, Steven T DeKosky, Stephan Schmidt","doi":"10.1371/journal.pmed.1004620","DOIUrl":"10.1371/journal.pmed.1004620","url":null,"abstract":"<p><strong>Background: </strong>The safety of pharmacokinetic opioid-antidepressant interactions may be affected by the sequence in which the drug is initiated. Previous literature showed that initiation of cytochrome P450 (CYP) 2D6-inhibiting versus CYP2D6-neutral antidepressants concomitantly with existing CYP2D6-metabolized opioids (i.e., antidepressant-triggered interaction) was associated with heightened risks of adverse outcomes (e.g., worsening pain). However, little is known about whether and to what extent the risks exist when CYP2D6-metabolized opioids are initiated on existing antidepressants (i.e., opioid-triggered interaction), a more common pattern of concomitant use of these two drugs. The study aims to examine the association of initiation of CYP2D6-metabolized opioids with risks of adverse outcomes among older nursing home residents who already received antidepressants.</p><p><strong>Methods and findings: </strong>We conducted a retrospective cohort study using a 100% Medicare nursing home sample linked to Medicare claims and Minimum Data Set (MDS) assessments from January 1, 2010, to December 31, 2021. Participants included long-term care residents 65 years of age or older who initiated CYP2D6-metabolized opioids while already receiving antidepressants for at least 30 days. The key exposure was the use of CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants concomitantly with CYP2D6-metabolized opioids, with day 1 of antidepressant-opioid concomitant use designated as cohort entry. Patients were followed from cohort entry until the end of 1 year, nursing home discharge, death, or study end (12/31/2021). Seven adverse outcomes included worsening pain, physical function, and depression, and counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose (OD). We identified 127,200 older nursing home long-term residents who initiated CYP2D6-metabolized opioids while already receiving antidepressants (mean [SD] age, 84.4 [8.7] years). After covariate adjustment via inverse probability of treatment weighting, use of CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants concomitantly with CYP2D6-metabolized opioids was associated with a higher risk of worsening pain (relative risk:1.04 [95% CI, 1.02, 1.06]; P < 0.001; risk difference (RD): 1.1% [95% CI, 0.6%, 1.6%]) and a higher incidence rate of pain-related hospitalizations (incidence rate ratio [IRR]:1.13 [95% CI, 1.04, 1.22]; P = 0.003; RD: 1.21 [95% CI, 0.39, 1.89] per 1,000 patient-years) and pain-related ED visits (IRR = 1.17 [95% CI, 1.07, 1.29]; P = 0.003; RD: 0.85 [95% CI, 0.29, 1.41] per 1,000 patient-years), with no difference in physical function, depression, OUD, and OD. Main study limitations included unmeasured confounding and limited generalizability.</p><p><strong>Conclusion: </strong>This cohort study of older nursing home residents showed that initiation of CYP2D6-metabolized opioids on existing ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004620"},"PeriodicalIF":15.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of lung function and severity grading in interstitial lung diseases (% predicted versus z-scores) and association with survival: A retrospective cohort study of 6,808 patients.","authors":"Piotr W Boros, Magdalena M Martusewicz-Boros, Katarzyna B Lewandowska","doi":"10.1371/journal.pmed.1004619","DOIUrl":"10.1371/journal.pmed.1004619","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary function tests (PFTs) are essential for predicting outcomes in interstitial lung disease (ILD). In 2022, an expert panel recommended using z-scores instead of the traditional % predicted cut-off values to interpret the severity of PFT abnormalities which may lead to discordant classifications in some patients. To assess the magnitude and prognostic impact of this phenomenon we compared these two approaches in predicting all-cause mortality in a large cohort of patients with ILDs.</p><p><strong>Methods and findings: </strong>We retrospectively analyzed data from a tertiary referral center for patients with ILDs. Absolute FEV1, FVC, TLC, and TLCO values from patients' first presentations were transformed and presented as % predicted and z-scores using the most recent global lung initiative (GLI) reference values. Results were categorized for severity according to % predicted and z-score levels. Predictors of all-cause mortality over a 14-year follow-up were determined using Kaplan-Meier survival analysis and Cox proportional hazards regression. Between January 2009 and March 2023, 6,808 patients with ILDs were evaluated at the National TB and Lung Diseases Research Institute in Warsaw, Poland. Most were diagnosed with sarcoidosis, fibrotic ILD, or non-fibrotic ILD. At their first presentation, 13.2% had airway obstruction, 23.1% had low FVC (indicative of restriction by spirometry), and 45.6% had a reduced lung transfer factor (TLCO). Reclassification of spirometric indices occurred in 26.8% of patients for FEV1 and 24.6% for FVC among those with abnormal results, with most being reassigned to a less severe categories. For TLCO, 28.1% of patients with reduced values were reclassified, with most shifting to more severe categories. During the follow-up, 1,525 (22.4%) of patients died. Both low FVC and low TLCO predicted all-cause mortality, with z-score thresholds showing stronger associations with mortality. A one-unit decrease in the FVC z-score was associated with a 10.3% increase in the risk of death, while a one-unit decrease in TLCO z-score was linked to an over 30% increase in mortality risk. Limitations of this retrospective single-center study include lack of data on cause-specific mortality, potential residual confounding, and limited generalizability to non-Caucasian or younger populations.</p><p><strong>Conclusions: </strong>The recently recommended use of z-scores leads to significant reclassification of lung function results in patients with ILDs, largely driven by age. This approach is justified by its stronger prognostic associations. Severe TLCO impairment remains a robust predictor of mortality in ILDs.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004619"},"PeriodicalIF":15.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty-year outcomes after repeat doses of antenatal corticosteroids prior to 32 weeks' gestation: Follow-up of a randomised clinical trial.","authors":"Robyn W May, Anthony G B Walters, Greg D Gamble, Caroline A Crowther, Stuart R Dalziel, Carl L Eagleton, Christopher J D McKinlay, Barry J Milne, Jane E Harding","doi":"10.1371/journal.pmed.1004618","DOIUrl":"10.1371/journal.pmed.1004618","url":null,"abstract":"<p><strong>Background: </strong>For women who have received a course of antenatal corticosteroids ≥7 days prior and have ongoing risk of preterm birth within the next 7 days, repeat dose(s) of corticosteroids up to 32 weeks' gestation have been shown to reduce neonatal respiratory distress syndrome and serious health problems in the neonatal period but not other neonatal morbidities such as chronic lung disease, death, severe intraventricular haemorrhage or necrotising enterocolitis. Repeat antenatal corticosteroids were not associated with either benefit or harms in mid-childhood. However, this may have been too early to evaluate potential adverse effects on respiratory and other long-term outcomes. We aimed to assess if exposure to repeat dose(s) of antenatal corticosteroids administered to pregnant women up to 32 weeks' gestation has beneficial or harmful effects on respiratory and general health of the offspring in adulthood.</p><p><strong>Methods and findings: </strong>We assessed the adult offspring of New Zealand participants in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids for the Prevention of Neonatal Respiratory Disease (ACTORDS), a multicentre, placebo-controlled trial where women at risk of preterm birth within the next week, 7 or more days after having received a single course of corticosteroids were randomised to a repeat dose of intramuscular betamethasone or placebo, that could be repeated weekly if at ongoing preterm birth risk. Follow-up at 20 years included a health questionnaire and consent to access administrative data sources. The primary outcome was any asthma diagnosis. Secondary outcomes included neurodevelopmental, cardiovascular, mental and general health, functional difficulties and social outcomes. Of 352 infants born to 290 maternal trial participants, we assessed 214 (61%; 96 (45%) female) at mean (standard deviation) age 20.5 (1.5) years. The rate of any asthma diagnosis was similar in both groups (58/107 (54%) repeat bethamethasone versus 50/107 (47%) placebo; risk ratio adjusted for gestational age at trial entry, multiplicity and birth centre 1.13, 95% confidence interval, 0.87, 1.46). Differences between the groups for the secondary outcomes were generally small and confidence intervals included the possibility of no difference between groups.</p><p><strong>Conclusions: </strong>In this follow-up of a randomised clinical trial, our data suggest neither major harm nor benefit for the offspring in early adulthood following exposure to repeat dose(s) of antenatal corticosteroids compared with a single course prior to 32 weeks' gestation. Smaller effects cannot be excluded and follow-up of adult offspring from other trials of repeat antenatal corticosteroids is recommended.</p><p><strong>Trial registration: </strong>International Standard Randomized Controlled Trial, number ISRCTN48656428.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004618"},"PeriodicalIF":15.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Power in numbers: Harnessing global data to unravel the alcohol-pancreatic cancer link.","authors":"Gilaad G Kaplan","doi":"10.1371/journal.pmed.1004615","DOIUrl":"10.1371/journal.pmed.1004615","url":null,"abstract":"<p><p>The global burden of pancreatic cancer is substantial, highlighting the need to identify modifiable risk factors. In a multi-country study, Sabine Naudin and colleagues demonstrate a clear association between alcohol consumption and the risk of pancreatic cancer.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004615"},"PeriodicalIF":15.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Determining optimal timing of birth for women with chronic or gestational hypertension at term: The WILL (When to Induce Labour to Limit risk in pregnancy hypertension) randomised trial.","authors":"Laura A Magee, Katie Kirkham, Sue Tohill, Eleni Gkini, Catherine A Moakes, Jon Dorling, Marcus Green, Jennifer A Hutcheon, Mishal Javed, Jesse Kigozi, Ben W M Mol, Joel Singer, Pollyanna Hardy, Clive Stubbs, James G Thornton, Peter von Dadelszen","doi":"10.1371/journal.pmed.1004627","DOIUrl":"10.1371/journal.pmed.1004627","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pmed.1004481.].</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004627"},"PeriodicalIF":15.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term exposure to ambient temperature variability and myocardial infarction hospital admissions: A nationwide case-crossover study in Sweden.","authors":"Wenli Ni, Massimo Stafoggia, Siqi Zhang, Petter Ljungman, Susanne Breitner, Jeroen de Bont, Tomas Jernberg, Dan Atar, Alexandra Schneider, Stefan Agewall","doi":"10.1371/journal.pmed.1004607","DOIUrl":"10.1371/journal.pmed.1004607","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Climate change threatens human health and general welfare via multiple dimensions. However, the associations of short-term exposure to temperature variability, a crucial aspect of climate change, with myocardial infarction (MI) hospital admissions remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;This population-based nationwide study employed a time-stratified, case-crossover design to investigate the association between ambient temperature variability and MI hospital admissions among 233,617 patients recorded in the SWEDEHEART registry in Sweden between 2005 and 2019. High-resolution (1 × 1 km) daily mean ambient temperature was assigned to patients' residential areas. Temperature variability was calculated as the difference between the same-day (as the MI event) ambient temperature and the average temperature over the preceding 7 days. An upward temperature shift represents a rise in the current day's temperature relative to the 7-day average, while a downward temperature shift indicates a corresponding decrease. A conditional logistic regression model with distributed lag non-linear model was applied to estimate the association between ambient temperature variability and total MI (encompassing all MI types), ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) hospital admissions at lag 0-6 days. Potential effect modifiers, such as sex, history of diseases, and season, were also examined. The patients had an average age of 70.6 years, and 34.5% of them were female. Our study found that an upward temperature shift was associated with increased risks of total MI (encompassing all MI types), STEMI, and NSTEMI hospital admissions at lag 0 day, with odds ratios (OR, 95% confidence intervals [CIs]) of 1.009 (1.005, 1.013; p &lt; 0.001), 1.014 (1.006, 1.022; p &lt; 0.001), and 1.007 (1.001, 1.012; p = 0.014) per 1 °C increase, respectively. These associations attenuated and became non-significant over lags 1-6 days. Furthermore, a downward temperature shift was associated with increased risks of hospital admissions for total MI (encompassing all MI types) at a lag of 2 days with an OR (95% CI): 1.003 (1.001, 1.005; p = 0.014), and for STEMI at lags 2 and 3 days with ORs (95% CI): 1.006 (1.002, 1.010; p = 0.001) and 1.005 (1.001, 1.008; p = 0.011), per 1 °C decrease, respectively. Conversely, higher downward temperature shifts were associated with decreased risks of total MI (encompassing all MI types) and NSTEMI at lag 0 day. No significant associations were observed at other lag days for downward temperature shifts. Males and patients with diabetes had higher MI hospitalization risks from upward temperature shift exposure, while downward temperature shift exposure in cold seasons posed greater MI hospitalization risks. A methodological limitation was the use of ambient temperature variability as a proxy for personal exposure, which, while practical for l","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004607"},"PeriodicalIF":15.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focussing on the origins of preterm birth: Why understanding aetiology is critical to optimising outcomes.","authors":"Jennifer Jardine, Laura Goodfellow, Caroline Ovadia, Anna L David, Catherine Williamson","doi":"10.1371/journal.pmed.1004601","DOIUrl":"10.1371/journal.pmed.1004601","url":null,"abstract":"<p><p>Preterm birth is a central determinant of infant morbidity and mortality. Efforts to reduce its incidence must address the disparate underlying causes.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004601"},"PeriodicalIF":15.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of poly-metabolite scores for diets high in ultra-processed food: An observational study and post-hoc randomized controlled crossover-feeding trial.","authors":"Leila Abar, Eurídice Martínez Steele, Sang Kyu Lee, Lisa Kahle, Steven C Moore, Eleanor Watts, Caitlin P O'Connell, Charles E Matthews, Kirsten A Herrick, Kevin D Hall, Lauren E O'Connor, Neal D Freedman, Rashmi Sinha, Hyokyoung G Hong, Erikka Loftfield","doi":"10.1371/journal.pmed.1004560","DOIUrl":"10.1371/journal.pmed.1004560","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ultra-processed food (UPF) accounts for a majority of calories consumed in the United States, but the impact on human health remains unclear. We aimed to identify poly-metabolite scores in blood and urine that are predictive of UPF intake.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Of the 1,082 Interactive Diet and Activity Tracking in AARP (IDATA) Study (clinicaltrials.gov ID NCT03268577) participants, aged 50-74 years, who provided biospecimen consent, n = 718 with serially collected blood and urine and one to six 24-h dietary recalls (ASA-24s), collected over 12-months, met eligibility criteria and were included in the metabolomics analysis. Ultra-high performance liquid chromatography with tandem mass spectrometry was used to measure &gt;1,000 serum and urine metabolites. Average daily UPF intake was estimated as percentage energy according to the Nova system. Partial Spearman correlations and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to estimate UPF-metabolite correlations and build poly-metabolite scores of UPF intake, respectively. Scores were tested in a post-hoc analysis of a previously conducted randomized, controlled, crossover-feeding trial (clinicaltrials.gov ID NCT03407053) of 20 subjects who were admitted to the NIH Clinical Center and randomized to consume ad libitum diets that were 80% or 0% energy from UPF for 2 weeks immediately followed by the alternate diet for 2 weeks; eligible subjects were between 18-50 years old with a body mass index of &gt;18.5 kg/m2 and weight-stable. IDATA participants were 51% female, and 97% completed ≥4 ASA-24s. Mean intake was 50% energy from UPF. UPF intake was correlated with 191 (of 952) serum and 293 (of 1,044) 24-h urine metabolites (FDR-corrected P-value &lt; 0.01), including lipid (n = 56 serum, n = 22 24-h urine), amino acid (n = 33, 61), carbohydrate (n = 4, 8), xenobiotic (n = 33, 70), cofactor and vitamin (n = 9, 12), peptide (n = 7, 6), and nucleotide (n = 7, 10) metabolites. Using LASSO regression, 28 serum and 33 24-h urine metabolites were selected as predictors of UPF intake; biospecimen-specific scores were calculated as a linear combination of selected metabolites. Overlapping metabolites included (S)C(S)S-S-Methylcysteine sulfoxide (rs = -0.23, -0.19), N2,N5-diacetylornithine (rs = -0.27 for serum, -0.26 for 24-h urine), pentoic acid (rs = -0.30, -0.32), and N6-carboxymethyllysine (rs = 0.15, 0.20). Within the cross-over feeding trial, the poly-metabolite scores differed, within individual, between UPF diet phases (P-value for paired t test &lt; 0.001). IDATA Study participants were older US adults whose diets may not be reflective of other populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Poly-metabolite scores, developed in IDATA participants with varying diets, are predictive of UPF intake and could advance epidemiological research on UPF and health. Poly-metabolite scores should be evaluated and iteratively improved in ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004560"},"PeriodicalIF":15.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol intake and pancreatic cancer risk: An analysis from 30 prospective studies across Asia, Australia, Europe, and North America.","authors":"Sabine Naudin, Molin Wang, Niki Dimou, Elmira Ebrahimi, Jeanine Genkinger, Hans-Olov Adami, Demetrius Albanes, Ana Babic, Matt Barnett, David Bogumil, Hui Cai, Chu Chen, A Heather Eliassen, Jo L Freudenheim, Gretchen Gierach, Edward L Giovannucci, Marc J Gunter, Niclas Håkansson, Mayo Hirabayashi, Tao Hou, Brian Z Huang, Wen-Yi Huang, Harindra Jayasekara, Michael E Jones, Verena A Katzke, Woon-Puay Koh, James V Lacey, Ylva Trolle Lagerros, Susanna C Larsson, Linda M Liao, Kenneth Lo, Erikka Loftfield, Robert J MacInnis, Satu Männistö, Marjorie L McCullough, Anthony Miller, Roger L Milne, Steven C Moore, Lorelei A Mucci, Marian L Neuhouser, Alpa V Patel, Elizabeth A Platz, Anna Prizment, Kim Robien, Thomas E Rohan, Carlotta Sacerdote, Sven Sandin, Norie Sawada, Minouk Schoemaker, Xiao-Ou Shu, Rashmi Sinha, Linda Snetselaar, Meir J Stampfer, Rachael Stolzenberg-Solomon, Cynthia A Thomson, Anne Tjønneland, Caroline Y Um, Piet A van den Brandt, Kala Visvanathan, Sophia S Wang, Renwei Wang, Elisabete Weiderpass, Stephanie J Weinstein, Emily White, Walter Willett, Alicja Woslk, Brian M Wolpin, Shiaw-Shyuan S Yaun, Chen Yuan, Jian-Min Yuan, Wei Zheng, Paul Brennan, Stephanie A Smith-Warner, Pietro Ferrari","doi":"10.1371/journal.pmed.1004590","DOIUrl":"10.1371/journal.pmed.1004590","url":null,"abstract":"<p><strong>Background: </strong>Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.</p><p><strong>Methods and findings: </strong>Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America. A total of 2,494,432 participants without cancer at baseline (62% women, 84% European ancestries, 70% alcohol drinkers [alcohol intake ≥ 0.1 g/day], 47% never smokers) were recruited between 1980 and 2013 at the median age of 57 years and 10,067 incident pancreatic cancer cases were recorded. In age- and sex-stratified Cox proportional hazards models adjusted for smoking history, diabetes status, body mass index, height, education, race and ethnicity, and physical activity, pancreatic cancer hazard ratios (HR) and 95% confidence intervals (CI) were estimated for categories of alcohol intake and in continuous for a 10 g/day increase. Potential heterogeneity by sex, smoking status, geographic regions, and type of alcoholic beverage was investigated. Alcohol intake was positively associated with pancreatic cancer risk, with HR30-to-<60 g/day and HR≥60 g/day equal to 1.12 (95% CI [1.03,1.21]) and 1.32 (95% CI [1.18,1.47]), respectively, compared to intake of 0.1 to <5 g/day. A 10 g/day increment of alcohol intake was associated with a 3% increased pancreatic cancer risk overall (HR: 1.03; 95% CI [1.02,1.04]; pvalue < 0.001) and among never smokers (HR: 1.03; 95% CI [1.01,1.06]; pvalue = 0.006), with no evidence of heterogeneity by sex (pheterogeneity = 0.274) or smoking status (pheterogeneity = 0.624). Associations were consistent in Europe-Australia (HR10 g/day = 1.03, 95% CI [1.00,1.05]; pvalue = 0.042) and North America (HR10 g/day = 1.03, 95% CI [1.02,1.05]; pvalue < 0.001), while no association was observed in cohorts from Asia (HR10 g/day = 1.00, 95% CI [0.96,1.03]; pvalue = 0.800; pheterogeneity = 0.003). Positive associations with pancreatic cancer risk were found for alcohol intake from beer (HR10 g/day = 1.02, 95% CI [1.00,1.04]; pvalue = 0.015) and spirits/liquor (HR10 g/day = 1.04, 95% CI [1.03,1.06]; pvalue < 0.001), but not wine (HR10 g/day = 1.00, 95% CI [0.98,1.03]; pvalue = 0.827). The differential associations across geographic regions and types of alcoholic beverages might reflect differences in drinking habits and deserve more investigations.</p><p><strong>Conclusions: </strong>Findings from this large-scale pooled analysis support a modest positive association between alcohol intake and pancreatic cancer risk, irrespective of sex and smoking status. Associations were particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004590"},"PeriodicalIF":15.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of a reduced dose of ready-to-use therapeutic food in community-based management of severe acute malnutrition: A non-inferiority randomized controlled trial in the Democratic Republic of Congo.","authors":"Julien Ntaongo Alendi, Cécile Salpeteur, Steve Botomba, Alemayehu Argaw, Victor Nikièma, Jean-Baptiste Mayavanga, Benjamin Guesdon, Marie Petry, Uwimana Sebinwa, Sophie Bruneau, Aimée Mupuala Masaya, Florence Mbiya Muadi, Samuel Mampunza Ma Miezi, Marie-Claire Muyer","doi":"10.1371/journal.pmed.1004606","DOIUrl":"10.1371/journal.pmed.1004606","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The reduced Ready-to-use Therapeutic Food (RUTF) dose strategy was demonstrated effective in recovering children with Severe Acute Malnutrition (SAM) in ideal conditions and in a context of food security. The present study was conducted to provide further evidence on the effectiveness of reduced RUTF dose in a context of high food insecurity and post conflict humanitarian crisis, and with routine health staff.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;An individually randomized non-inferiority trial was conducted in 968 children aged 6-59 months suffering from SAM without medical complications in 14 health centers in the Bonzola and Nzaba health zones of Kasaï Oriental, Democratic Republic of Congo (DRC). Children were randomly assigned to either a control group receiving the standard WHO (World Health Organization) RUTF dose at the time or an intervention group receiving a reduced RUTF dose starting from the third week of treatment. The primary outcome was weight gain velocity from admission to discharge from treatment, while secondary outcomes included anthropometry measurements, programmatic outcomes and relapse. Mixed effects linear and logistic regression models with the health center as random intercept were used to compare differences between the two study groups. Close to 94% of the children were from severely food insecure households. There was no difference in weight gain velocity between the two groups (4.88 ± 2.36 g/kg/d reduced dose group versus 5.09 ± 2.28 g/kg/d standard dose group; difference -0.09 g/kg/d (95% CI [-0.33, 0.15]; p = 0.46). Programmatic outcomes were also similar between the two groups: recovery rate (64.3% versus 67.0%), loss to follow-up (4.69% versus 5.23%), defaulter rate (2.65% and 1.88%), relapse rate over 3 months (2.86% versus 2.40%) and mean length of stay (42 versus 43 days). Nevertheless, the rate of mid-upper arm circumference (MUAC) gain from the third week onwards was lower in the reduced-dose group than in the standard-dose group, with a mean difference of -0.13 mm/week (95% CI [-0.25, -0.01]; p = 0.04). There was no difference in terms of serious adverse events, in the reduced versus standard dose: weight loss (2.24% versus 1.26%), weight stagnation (14.9% versus 17.0%), and medical complications (4.08% versus 3.77%). Important effect modifiers identified were: child sex, child age, season of admission and missed treatment visits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The strategy of a reduced RUTF dose starting from the third week of treatment is as effective as the standard dose strategy on weight gain velocity and programmatic outcomes in a context of severe food insecurity. However, MUAC gain velocity was lower in the reduced dose group. Future studies should investigate the effectiveness of a reduced dose strategy among sub group of children with high risk factors. Trial registration: International Standard Randomized Controlled Trial Network (ISRCTN15258669).&lt;","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004606"},"PeriodicalIF":15.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}