{"title":"Decline in US Overdose Deaths May Be Tied to Fentanyl Disruption.","authors":"Samantha Anderer","doi":"10.1001/jama.2025.23028","DOIUrl":"https://doi.org/10.1001/jama.2025.23028","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Limited Evidence Supporting Melatonin Use in Most Children.","authors":"Samantha Anderer","doi":"10.1001/jama.2025.23029","DOIUrl":"https://doi.org/10.1001/jama.2025.23029","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne W T van der Wel,Joop S E Laven,Bas B van Rijn
{"title":"Prevention of Pregnancy Complications in Polycystic Ovary Syndrome With Myo-inositol Supplementation-Reply.","authors":"Anne W T van der Wel,Joop S E Laven,Bas B van Rijn","doi":"10.1001/jama.2025.22971","DOIUrl":"https://doi.org/10.1001/jama.2025.22971","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"180 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heather E Whitson,Nicole R Fowler,Michelle M Mielke
{"title":"Blood-Based Biomarkers for Alzheimer Disease: Preventing Unintended Consequences.","authors":"Heather E Whitson,Nicole R Fowler,Michelle M Mielke","doi":"10.1001/jama.2025.26049","DOIUrl":"https://doi.org/10.1001/jama.2025.26049","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philip L Molyneaux,Nesrin Mogulkoc,Hakan Gunen,Anna Doboszynska,Michael Kreuter,Blue Neustifter,Vandana Mathur,James Cassella,
ImportanceFor patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed.ObjectiveTo determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough.Design, Setting, and ParticipantsIn this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025.InterventionPatients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks.Main Outcomes and MeasuresThe primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6.ResultsOf the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2% (from 31.5 to 11.9; P < .001), respectively, compared with placebo (16.9%; from 29.4 to 28.1 coughs/h). For the key secondary outcome of patient-reported cough frequency at week 6, the relative and absolute changes were -31.4% (from 2.3 to 1.5; P = .14), -40.6% (from 2.6 to 1.4; P = .004), and -40.2% (from 2.4 to 1.4; P < .005) in the 27-mg, 54-mg, and 108-mg groups, respectively, compared with -21.9% (from 2.6 to 1.9) with placebo.Conclusions and RelevanceFor patients with IPF-associated chronic cough, all 3 doses of nalbuphine ER reduced objective cough frequency and the 2 higher doses improved patient-reported cough frequency at 6 weeks.Trial RegistrationClinicalTrials.gov Identifier: NCT05964335.
{"title":"Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial.","authors":"Philip L Molyneaux,Nesrin Mogulkoc,Hakan Gunen,Anna Doboszynska,Michael Kreuter,Blue Neustifter,Vandana Mathur,James Cassella, ","doi":"10.1001/jama.2025.26179","DOIUrl":"https://doi.org/10.1001/jama.2025.26179","url":null,"abstract":"ImportanceFor patients with idiopathic pulmonary fibrosis (IPF), cough impairs quality of life; effective treatments for IPF-associated cough are needed.ObjectiveTo determine if nalbuphine extended release (ER), a κ opioid receptor agonist and μ-opioid receptor antagonist, decreases cough compared with placebo in patients with IPF-associated cough.Design, Setting, and ParticipantsIn this randomized, double-blind, placebo-controlled phase 2b trial conducted at 52 sites in 10 countries, patients with IPF, chronic cough for at least 8 weeks, and a Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) score of 4 or higher were enrolled from February 2024 to February 2025, with last follow-up in April 2025. Statistical analyses were conducted from May to August 2025.InterventionPatients were randomized 1:1:1:1 to receive nalbuphine ER at doses of 27 mg, 54 mg, or 108 mg or placebo twice daily for 6 weeks.Main Outcomes and MeasuresThe primary outcome was the relative change from baseline in 24-hour cough frequency (coughs/h), measured with a digital cough monitor, for nalbuphine ER compared with placebo at week 6. The key secondary outcome was the relative change from baseline in the patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores indicate lesser cough frequency) at week 6.ResultsOf the 223 patients screened, 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively) and 160 were included in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female). The baseline mean (SD) cough count was 28.3 (27.4) coughs/h. In the nalbuphine ER 27 mg, 54 mg, and 108 mg twice-daily groups, the mean relative decrease in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P = .008), 53.4% (from 28.0 to 14.9; P < .001), and 60.2% (from 31.5 to 11.9; P < .001), respectively, compared with placebo (16.9%; from 29.4 to 28.1 coughs/h). For the key secondary outcome of patient-reported cough frequency at week 6, the relative and absolute changes were -31.4% (from 2.3 to 1.5; P = .14), -40.6% (from 2.6 to 1.4; P = .004), and -40.2% (from 2.4 to 1.4; P < .005) in the 27-mg, 54-mg, and 108-mg groups, respectively, compared with -21.9% (from 2.6 to 1.9) with placebo.Conclusions and RelevanceFor patients with IPF-associated chronic cough, all 3 doses of nalbuphine ER reduced objective cough frequency and the 2 higher doses improved patient-reported cough frequency at 6 weeks.Trial RegistrationClinicalTrials.gov Identifier: NCT05964335.","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca L Siegel,Nikita Sandeep Wagle,Ahmedin Jemal
{"title":"Leading Cancer Deaths in People Younger Than 50 Years.","authors":"Rebecca L Siegel,Nikita Sandeep Wagle,Ahmedin Jemal","doi":"10.1001/jama.2025.25467","DOIUrl":"https://doi.org/10.1001/jama.2025.25467","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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