PLoS Medicine最新文献

{"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}

{"title":"The comparative effectiveness and safety of fluticasone-salmeterol via metered-dose versus dry powder inhalers for COPD: A new user cohort study.","authors":"Brandon J Demkowicz, Kevin Rader, Shirley V Wang, Aaron S Kesselheim, William B Feldman","doi":"10.1371/journal.pmed.1004596","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004596","url":null,"abstract":"<p><strong>Background: </strong>Fluticasone-salmeterol is available in both metered-dose and dry powder inhaler formulations for the treatment of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers are associated with substantially higher greenhouse gas emissions than dry powder inhalers; however, data on their comparative effectiveness and safety in COPD remain limited. We aimed to compare the effectiveness and safety of fluticasone-salmeterol delivered via metered-dose inhaler (Advair HFA) versus dry powder inhaler (Advair Diskus) among patients with COPD treated in routine care.</p><p><strong>Methods and findings: </strong>We conducted a retrospective cohort study using Optum's de-identified Clinformatics DataMart (January 1, 2007 to November 30, 2023). The study included 202,052 commercially insured patients aged 40 years or older with COPD who had continuous insurance coverage for 180 days prior to cohort entry and had not initiated any inhaled corticosteroid-long-acting β₂-agonist during that period. Patients receiving fluticasone-salmeterol via a metered-dose inhaler (exposure) were compared to those receiving these drugs via a dry powder inhaler (referent), with stabilized inverse probability of treatment weighting applied for covariate adjustment. The primary effectiveness outcome was the incidence of first moderate or severe COPD exacerbation within 365 days of cohort entry. The primary safety outcome was the incidence of first pneumonia hospitalization during the same period. Use of fluticasone-salmeterol via metered-dose inhaler was associated with a similar hazard of first moderate or severe COPD exacerbation (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.99 to 1.08) and first pneumonia hospitalization (HR, 1.06; 95% CI, 0.98 to 1.14) compared to the dry powder inhaler. Primary study limitations include potential residual confounding despite weighting and short follow-up times.</p><p><strong>Conclusions: </strong>In this cohort study comparing two brand-name fluticasone-salmeterol inhalers prescribed for COPD in routine clinical practice, effectiveness and safety outcomes were similar for patients receiving metered-dose and dry powder versions.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004596"},"PeriodicalIF":15.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080670","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":"Safety and tolerability of intravenous liposomal GM1 in patients with Parkinson disease: A single-center open-label clinical phase I trial (NEON trial).","authors":"Stefan Halbherr, Stefanie Lerch, Sebastian Bellwald, Petra Polakova, Bettina Bannert, Marie Roumet, Roch-Philippe Charles, Martin A Walter, Corrado Bernasconi, Valérie Lisa Halbherr, Camille Peitsch, Pascal C Baumgartner, Céline Kaufmann, Vanessa Aires, Heinrich P Mattle, Alain Kaelin-Lang, Andreas Hartmann, Michael Schuepbach","doi":"10.1371/journal.pmed.1004472","DOIUrl":"10.1371/journal.pmed.1004472","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Parkinson disease (PD) is a chronic progressive neurodegenerative disorder leading to motor and non-motor impairment, often resulting in severe loss of quality of life. There are symptomatic treatments without effect on the progression of PD. A disease-modifying treatment that could ideally stop the neurodegenerative process is direly needed. Monosialotetrahexosylganglioside (GM1) is a promising molecule with neuroprotective effects in preclinical models of PD and has yielded encouraging results in patients with PD in a randomized placebo-controlled trial. Talineuren (TLN) is a liposomal formulation of GM1 that has been shown to cross the blood-brain barrier in animals. We assessed the safety and pharmacokinetics (PK) of TLN in patients with PD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We prospectively enrolled 12 patients with PD into a single-center, open-label phase I trial to assess the safety and tolerability of weekly infusions with TLN. The maximum suitable dose of TLN was determined by dose escalation in three patients. All three patients tolerated the predetermined maximal dose of 720 mg. Subsequently, these and nine additional patients received weekly infusions at the maximum suitable dose of 720 mg TLN over two months (1 patient stopped prematurely). PK were determined for the additional nine patients as a secondary outcome measure. Cmax was reached 4 h after infusion start for all but one participant, who reached Cmax after 1 h, while the median plasma half-life was reached at 12.6 h. All adverse events were continuously assessed as the primary objective and coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Clinical manifestations of PD were assessed as secondary outcomes using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), including a levodopa challenge test at baseline and end. In addition to weekly history taking, scales to measure mood, behavior, quality of life, sleepiness, non-motor symptoms of PD, and cognition were used as further secondary outcomes as well as assessing the Levodopa-Equivalent Daily Dose (LEDD). Overall, 304 adverse events (mean: 25.33; 6-75 events per patient) occurred, 267 of which were mild (mean: 22.25; 3-72 events per patient). 23 were considered related to the study treatment (0-8 events per patient). Very mild-to-severe acute infusion reactions at the second, third, or fourth administration of TLN within the first minutes of the infusion occurred in seven patients. All reported back or neck pain. Other acute infusion reactions were urticaria, plethora, nausea, and chest pain. These adverse reactions disappeared within minutes of stopping the infusion and did not recur when TLN administration was resumed at a very low rate. Beyond the fourth administration, infusions could be given at increased rates up to 370 ml/h, and no acute reaction occurred anymore. The mechanism of this acute infusion reaction rem","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004472"},"PeriodicalIF":15.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042533","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":"Change in willingness for surgery and risk of joint replacement after an education and exercise program for hip/knee osteoarthritis: A longitudinal cohort study of 55,059 people.","authors":"Belinda J Lawford, Ali Kiadaliri, Martin Englund, Kim L Bennell, Rana S Hinman, Michelle Hall, Andrea Dell'Isola","doi":"10.1371/journal.pmed.1004577","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004577","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Numerous studies report that education and exercise interventions can shift people's willingness to undergo joint replacement surgery for osteoarthritis. We aimed to investigate whether becoming unwilling to undergo surgery following an education and exercise intervention for hip and knee osteoarthritis is associated with lower probability of receiving actual surgery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;This was a register-based cohort study including people from the Swedish Osteoarthritis Register who underwent a 3-month education and exercise intervention for knee or hip osteoarthritis. Participants self-reported their willingness to have joint replacement surgery ('yes' or 'no') and were grouped based on their response pre- and post-intervention (always willing for surgery; became unwilling for surgery; never willing for surgery; became willing for surgery). Data on joint replacement surgery was obtained through the Swedish Arthroplasty Register. The probability and hazard of surgery occurring, as well as the mean time without surgery was calculated up to 5-years (primary outcome) and 9-years (secondary outcome) post-intervention. We adjusted for age, sex, body mass index (BMI), education, joint pain, quality of life, walking difficulties, number of prior visits with an orthopedic surgeon, prior joint surgeries in the knee or hip (other than joint replacement), and comorbidities. 55,059 people were included, 69% were female (N = 37,739), with a mean age 66years (standard deviation [SD] = 9.3), and a BMI of 27.5 (SD = 4.9). In total, 70% (N = 38,386) were never willing for surgery, 14% (N = 7,736) were always willing for surgery, 10% (N = 5,649) became unwilling for surgery, and 6% (N = 3,288) became willing for surgery. Compared to those who were always willing for surgery, participants who became unwilling had a 20% (95% confidence interval [CI]: 18, 22%) lower probability of having surgery by 5-years post-intervention. This corresponded to delaying surgery by 1.1 (95% CI: 1.0, 1.1) years. Compared to those who were always willing for surgery, the hazard of surgery occurring at 1-year post-intervention was lower in those who became unwilling (hazard ratio (HR) 0.5 [95% CI: 0.4, 0.5]), though was then higher at 5-years (HR 1.4 [95% CI: 1.2, 1.7]). Estimates remained stable from 5 to 9 years. Limitations of our study include the inability to account for all potential confounders, and to infer the contribution of the intervention to change in willingness for surgery due to the absence of a control group. Data were collected in Sweden, generalisability to other countries may be limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Becoming unwilling for joint replacement surgery following an education and exercise program for hip and knee osteoarthritis could reduce the number of joint replacement surgeries by 20% at 5 years post-intervention, with the possibility of maintaining most of this reduction up to 9 years","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004577"},"PeriodicalIF":15.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005117","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}