BMJ medicine最新文献

{"title":"Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study.","authors":"Henock G Yebyo, Huldrych F Guenthard, Eva A Rehfuess, Nicola Serra, Sarah R Haile, Oliver Senn, Gregory M Lucas, Oliver Langselius, Jennifer E Thorne, Vincent C Marconi, Sally B Coburn, Raynell Lang, Jonathan A Colasanti, Michael J Silverberg, Sonia Napravnik, Mona Loutfy, Maile Karris, Timothy R Sterling, Greer A Burkholder, Keri N Althoff, Milo A Puhan","doi":"10.1136/bmjmed-2024-001132","DOIUrl":"10.1136/bmjmed-2024-001132","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.</p><p><strong>Design: </strong>Target trial and modelling study.</p><p><strong>Setting: </strong>North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-ACCORD integrates individual level data from >20 HIV cohorts across the US and Canada from people with HIV who have successfully linked into care.</p><p><strong>Participants: </strong>157 699 people with HIV enrolled in one of the cohorts of NA-ACCORD. 54 165 eligible individuals, aged 40-75 years, were enrolled in the target trial.</p><p><strong>Main outcome measures: </strong>The primary outcomes for the target trial were the 10 year effects of statins on cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcomes (type 2 diabetes, mild cognitive impairment, rhabdomyolysis, and myopathy). The secondary outcome was the 10 year risk threshold where the reduction in cardiovascular disease outweighed the increased risk of harm outcomes, showing an overall net benefit of statins.</p><p><strong>Results: </strong>Participants who first started receiving treatment with statins (statin initiators) had a 21% reduction in cardiovascular disease events (hazard ratio 0.79, 95% confidence interval (CI) 0.72 to 0.87) and a 26% reduction in the combined risk of stroke and myocardial infarction (0.74, 0.56 to 0.98), but a 12% increase in the risk of type 2 diabetes (1.12, 1.01 to 1.25) compared with participants who developed the indication but did not take statins (non-initiators). The effects on cognitive impairment (hazard ratio 1.13, 95% CI 0.82 to 1.56), myopathy (1.10, 0.76 to 1.61), and rhabdomyolysis (1.09, 0.68 to 1.75) were not statistically significant. On average, the benefit of statins exceeded harms for individuals with a 10 year baseline risk of cardiovascular disease of ≥13.8%. Subgroup specific thresholds included men (14.2%), women (11.1%), ages 40-64 years (13.8%) versus 65-75 years (15.1%), and CD4 count >200 cells/mm³ (13.6%) versus <200 cells/mm³ (15.3%). Varying weights for cardiovascular disease yielded thresholds ranging from 11.6% to 54.0%, whereas weights for harm outcomes resulted in thresholds ranging from 5.0% to >30.0%.</p><p><strong>Conclusions: </strong>In this study, statins benefitted individuals with HIV with a moderate or high risk of cardiovascular disease, but the threshold for net benefit varied by patient subgroup and preference, implying the need to customise statin treatment to individual risks, preferences, and treatment goals. Given the limitations of observational data, further controlled studies are needed to evaluate the efficacy and safety of statins in people with HIV receiving mode","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001132"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Design differences and variation in results between randomised trials and non-randomised emulations: meta-analysis of RCT-DUPLICATE data.","authors":"","doi":"10.1136/bmjmed-2023-000709corr1","DOIUrl":"https://doi.org/10.1136/bmjmed-2023-000709corr1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1136/bmjmed-2023-000709.].</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e000709corr1"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of stress management and relaxation interventions for management of hypertension and prehypertension: systematic review and network meta-analysis.","authors":"Katie E Webster, Monika Halicka, Russell J Bowater, Thomas Parkhouse, Dara Stanescu, Athitya Vel Punniyakotty, Jelena Savović, Alyson Huntley, Sarah Dawson, Christopher E Clark, Rachel Johnson, Julian Pt Higgins, Deborah M Caldwell","doi":"10.1136/bmjmed-2024-001098","DOIUrl":"10.1136/bmjmed-2024-001098","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess whether relaxation and stress management techniques are useful in reducing blood pressure in individuals with hypertension and prehypertension.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Systematic review and network meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources: &lt;/strong&gt;Medline, PsycInfo, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to 23 February 2024, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from inception to 27 February 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Eligibility criteria for selecting studies: &lt;/strong&gt;Studies published in English of adults with hypertension (blood pressure ≥140/90 mm Hg) or prehypertension (blood pressure ≥120/80 mm Hg but &lt;140/90 mm Hg). Studies that compared non-pharmacological interventions used to promote relaxation or reduce stress with each other, or with a control group (eg, no intervention, waiting list, or standard care). Where possible, network meta-analysis was used to compare the efficacy of the different interventions. Studies were assessed with the risk of bias 2 tool (RoB2), and those at high risk of bias were excluded from the primary analysis. The certainty of the evidence was assessed with CINeMA (Confidence in Network Meta-Analysis) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;182 studies were included (166 for hypertension and 16 for prehypertension). Results from a random effects network meta-analysis showed that, at short term follow-up (≤3 months), most relaxation interventions appeared to have a beneficial effect on systolic and diastolic blood pressure for individuals with hypertension. Between study heterogeneity was moderate (τ=2.62-4.73). Compared with a passive comparator (ie, no intervention, waiting list, or usual care), moderate reductions in systolic blood pressure were found for breathing control (mean difference -6.65 mm Hg, 95% credible interval -10.39 to -2.93), meditation (mean difference -7.71 mm Hg, -14.07 to -1.29), meditative movement (including tai chi and yoga, mean difference -9.58 mm Hg, -12.95 to -6.17), mindfulness (mean difference -9.90 mm Hg, -16.44 to -3.53), music (mean difference -6.61 mm Hg, -11.62 to -1.56), progressive muscle relaxation (mean difference -7.46 mm Hg, -12.15 to -2.96), psychotherapy (mean difference -9.83 mm Hg, -16.24 to -3.43), and multicomponent interventions (mean difference -6.78 mm Hg, -11.59 to -1.99). Reductions were also seen in diastolic blood pressure. Few studies conducted follow-up for more than three months, but effects on blood pressure seemed to lessen over time. Limited data were available for prehypertension; only two studies compared short term follow-up of relaxation therapies with a passive comparator, and the effects on systolic blood pressure were small (mean difference -3.84 mm Hg, 95% credible interval -6.25 to -1.43 for meditative movement; mean difference ","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001098"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loneliness and all cause mortality in Australian women aged 45 years and older: causal inference analysis of longitudinal data.","authors":"Neta HaGani, Philip Clare, Dafna Merom, Ben J Smith, Ding Ding","doi":"10.1136/bmjmed-2024-001004","DOIUrl":"10.1136/bmjmed-2024-001004","url":null,"abstract":"<p><strong>Objective: </strong>To examine the causal effects of loneliness on mortality among Australian women aged 45 years and older.</p><p><strong>Design: </strong>Causal inference analysis of longitudinal data.</p><p><strong>Participants: </strong>A population based sample of Australian women aged 45 years and older (n=11 412).</p><p><strong>Main outcome measures: </strong>Targeted maximum likelihood estimations were used to analyse the causal relationship between loneliness and all cause mortality over 18 years. The adjusted risk of death associated with the total number of loneliness waves (loneliness persistency) and the consecutive number of loneliness waves (loneliness chronicity) was presented using risk ratios and risk differences with 99.5% confidence intervals (CIs).</p><p><strong>Results: </strong>The association between the number of waves of reported loneliness and mortality risk showed a dose-dependent pattern. Compared with women who did not report loneliness in any wave, people who reported loneliness at two, four, and six waves had an incrementally higher risk of dying during the follow-up period: risk ratio 1.49 (99.5% CI 1.26 to 1.75) at two waves, 2.18 (1.79 to 2.66) at four waves, and 3.15 (2.35 to 4.23) at six waves. The risk difference showed a similar trend to the risk ratios with higher excess mortality among women who reported experiencing loneliness for six waves compared with those who did not report loneliness at all (10.86% (99.5% CI 10.58% to 11.15%)). Similar trends were found when loneliness was experienced across consecutive waves.</p><p><strong>Conclusions: </strong>Loneliness seems to be causally linked to mortality risk with a dose-dependent relationship. Acknowledging loneliness as an independent health risk underscores the importance of screening for loneliness and incorporating public health interventions into healthcare practices.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001004"},"PeriodicalIF":0.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits, burden, and harms of computer aided polyp detection with artificial intelligence in colorectal cancer screening: microsimulation modelling study.","authors":"Natalie Halvorsen, Cesare Hassan, Loredana Correale, Nastazja Pilonis, Lise M Helsingen, Marco Spadaccini, Alessandro Repici, Farid Foroutan, Per Olav Vandvik, Shanaz Sultan, Magnus Løberg, Mette Kalager, Yuichi Mori, Michael Bretthauer","doi":"10.1136/bmjmed-2025-001446","DOIUrl":"10.1136/bmjmed-2025-001446","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Objective: </strong>To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.</p><p><strong>Design: </strong>Microsimulation modelling study.</p><p><strong>Setting: </strong>Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.</p><p><strong>Population: </strong>Four cohorts of 100 000 European individuals aged 60-69 years.</p><p><strong>Intervention: </strong>The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.</p><p><strong>Main outcome measures: </strong>Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10 years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.</p><p><strong>Results: </strong>For 100 000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.</p><p><strong>Conclusion: </strong>With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001446"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Between promise and peril: role of suzetrigine as a non-opioid analgesic.","authors":"Jay Karri, Ryan S D'Souza, Steven P Cohen","doi":"10.1136/bmjmed-2025-001431","DOIUrl":"10.1136/bmjmed-2025-001431","url":null,"abstract":"","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001431"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between cardiometabolic comorbidities and mortality in adults with cancer: multinational cohort study.","authors":"Veronica Davila-Batista, Vivian Viallon, Emma Fontvieille, Anna Jansana, Mirjam Kohls, Nicola P Bondonno, Anne Tjønneland, Christina C Dahm, Christian S Antoniussen, Verena Katzke, Rashmita Bajrachaya, Matthias B Schulze, Claudia Agnoli, Fulvio Ricceri, Salvatore Panico, Raul Zamora-Ros, Miguel Rodriguez-Barranco, Pilar Amiano, Maria-Dolores Chirlaque, Conchi Moreno-Iribas, Keren Papier, Konstantinos K Tsilidis, Dagfinn Aune, Marc J Gunter, Elisabete Weiderpass, Mazda Jenab, Pietro Ferrari, Heinz Freisling","doi":"10.1136/bmjmed-2024-000909","DOIUrl":"10.1136/bmjmed-2024-000909","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Objective: </strong>To examine separate and joint associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer.</p><p><strong>Design: </strong>Multinational cohort study.</p><p><strong>Setting: </strong>Seven European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1 January 1992 to 31 December 2013.</p><p><strong>Participants: </strong>26 987 participants (54% women) who developed a first primary cancer. 2113 had a history of type 2 diabetes, 1529 had a history of cardiovascular disease, and 531 had a history of both, at the time of diagnosis of cancer.</p><p><strong>Main outcome measures: </strong>Hazard ratios (95% confidence intervals, CIs) for associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer, estimated with multivariable Cox regression models. Associations were also estimated by groups of five year relative survival of cancer (survival ≤40%, 40-80%, and ≥80%) according to Surveillance, Epidemiology, and End Results (SEER) statistics, and for the most common site specific cancers.</p><p><strong>Results: </strong>At the time of diagnosis of cancer, 84.5% (n=22 814) of participants had no history of a cardiometabolic disease, 7.8% (n=2113) had a history of type 2 diabetes, 5.7% (n=1529) had a history of cardiovascular disease, and 2.0% (n=531) had a history of both cardiovascular disease and type 2 diabetes. 12 782 deaths (10 492 cancer deaths) occurred over a mean follow-up period of 7.2 years. After multivariable adjustments, pre-existing comorbidities were positively associated with all cause mortality, with hazard ratios 1.25 (95% CI 1.17 to 1.34), 1.30 (1.21 to 1.39), and 1.60 (1.42 to 1.80) for participants with type 2 diabetes, cardiovascular disease, or both, respectively, compared with participants with no cardiometabolic comorbidity. Corresponding hazard ratios for cancer specific mortality were 1.13 (95% CI 1.05 to 1.22), 1.13 (1.04 to 1.23), and 1.33 (1.16 to 1.53), respectively. Associations for all cause mortality were stronger among participants with cancers with a five year relative survival ≥80%. In a subsample, duration of type 2 diabetes (P_interaction=0.73) or cardiovascular disease (P_interaction=0.24), categorised as <5 years or ≥5 years, did not modify associations between these comorbidities and all cause mortality.</p><p><strong>Conclusions: </strong>In this study, cardiovascular disease or type 2 diabetes, or a combination of both, before a diagnosis of cancer, was associated with increased mortality (all cause mortality, and cancer and cardiovascular disease specific mortality). These findings support a direct role of cardiometabolic comorbidities on the prognosis of cancer.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e000909"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of antibiotics in early life and development of diseases in childhood: nationwide registry study.","authors":"Sarah Brandt, Jonathan Thorsen, Morten Arendt Rasmussen, Bo Chawes, Klaus Bønnelykke, Martin J Blaser, Astrid Sevelsted, Jakob Stokholm","doi":"10.1136/bmjmed-2024-001064","DOIUrl":"10.1136/bmjmed-2024-001064","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between the use of antibiotics in early life and the development of immune mediated diseases in children and adolescents.</p><p><strong>Design: </strong>Nationwide registry study.</p><p><strong>Setting: </strong>National Danish registries: Danish Civil Registration System identified children born in Denmark; information on the use of antibiotics from the Danish National Prescription Registry; disease outcomes from the Danish National Prescription Registry and the Danish National Patient Registry; and relevant covariates from the Danish Medical Birth Register and the Employment Classification Module. Study period from 1 January 1998 to 31 December 2016.</p><p><strong>Participants: </strong>Of 648 507 children born in Denmark in 1998-2006, 518 483 resided in Denmark during their first year of life, had no disease outcomes before the age of one year, and formed the final study population. The sibling population was 272 753 (126 632 sibships).</p><p><strong>Main outcome measures: </strong>Risk of developing immune mediated diseases (asthma, allergy, eczema, coeliac disease, juvenile arthritis, and type 1 diabetes) and overweight in the total population and in a sibling matched cohort (to mitigate the influence of familial factors and unmeasured confounding), by survival analysis with Cox regression.</p><p><strong>Results: </strong>Children were followed up for a mean of 13.2 years (standard deviation 3.12). Among the total study population, 40.3% (n=209 013) of children were prescribed systemic antibiotics before the age of one year. Use of antibiotics was associated with an increased risk of several immune mediated diseases (adjusted hazard ratios 1.20-1.53). A dose-response relation was found. When analysing sibling pairs, only asthma and eczema outcomes (adjusted hazard ratios 1.07-1.35) were associated with the use of antibiotics. No specific trends about the timing of use or type of antibiotic were found.</p><p><strong>Conclusions: </strong>In this study, use of antibiotics in early life was linked with immune mediated diseases in childhood and adolescence, but familial and unmeasured factors within the family might provide partial explanations. The study emphasises the need to better understand the interactions between antibiotics, familial susceptibility, and immune mediated pathogenesis to identify potential preventive strategies.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001064"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness and prescribing trends of modified release versus immediate release indapamide in patients with hypertension: cohort study.","authors":"Vincent Ka Chun Yan, Chengsheng Ju, Thomas MacLennan MacDonald, Isla S Mackenzie, Robert Flynn, Bryan Williams, Yang Chen, Esther W Chan, Jacob George, Li Wei","doi":"10.1136/bmjmed-2024-000857","DOIUrl":"10.1136/bmjmed-2024-000857","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the prescribing trends of indapamide, a thiazide-like diuretic, and the long term comparative effectiveness of modified release versus immediate release indapamide.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Setting: </strong>IQVIA Medical Research Data UK database, incorporating data from The Health Improvement Network database, 1 January 2005 to 31 December 2020.</p><p><strong>Participants: </strong>Of 1 904 289 patients with hypertension, 86 388 started indapamide treatment during the study period. 30 021 patients received modified release and 56 367 immediate release indapamide.</p><p><strong>Main outcome measures: </strong>Monthly prescribing trends of modified release and immediate release indapamide are described. A pragmatic trial was emulated to compare the five year risks of composite cardiovascular events (myocardial infarction and stroke) and death between modified release and immediate release indapamide. Intention-to-treat and per protocol effects of treatment were estimated with pooled logistic regression models. Confounding and selection bias were accounted for by multivariable adjustments and inverse probability weights.</p><p><strong>Results: </strong>1 38 414 patients who used indapamide were identified among 1 904 289 patients with hypertension. A greater increase was seen in the proportion of users of immediate release indapamide (from 0.43% in 2005 to 2.31% in 2020) than in users of modified release indapamide (from 0.71% to 0.79%). 86 388 patients (30 021 and 56 367 who started modified release and immediate release indapamide, respectively) were eligible for the trial emulation. In the intention-to-treat analysis, no difference was found in the risk of cardiovascular events (hazard ratio 0.99, 95% confidence interval (CI) 0.90 to 1.08) or death (hazard ratio 0.97, 0.92 to 1.02) between modified release and immediate release indapamide. In the per protocol analysis, a lower risk of cardiovascular events was found with modified release indapamide than with immediate release indapamide (risk difference -0.39%, 95% CI -0.71% to -0.06%; hazard ratio 0.81, 95% CI 0.68 to 0.98), which was mainly driven by myocardial infarction (risk difference -0.36%, 95% CI -0.64% to -0.08%; hazard ratio 0.80, 95% CI 0.64 to 1.01). Similar risks of death (hazard ratio 1.03, 95% CI 0.90 to 1.17) were found for the two formulations.</p><p><strong>Conclusions: </strong>In patients treated with indapamide for hypertension, starting treatment with modified release or immediate release indapamide had similar risks for cardiovascular events or all cause mortality. In an exploratory secondary analysis, sustained treatment with modified release preparations was associated with a lower the risk of cardiovascular events but not all cause mortality compared with immediate release preparations. These findings need to be confirmed in prospective studies.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e000857"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bladder drugs and risk of dementia: Danish nationwide active comparator study.","authors":"Nelsan Pourhadi, Janet Janbek, Christiane Gasse, Thomas Munk Laursen, Amani Meaidi, Christina Jensen-Dahm, Gunhild Waldemar","doi":"10.1136/bmjmed-2024-001125","DOIUrl":"10.1136/bmjmed-2024-001125","url":null,"abstract":"<p><strong>Objective: </strong>To assess the association between cumulative use of anticholinergic bladder drugs and risk of all cause dementia compared with non-use and use of the β3 agonist bladder drug, mirabegron.</p><p><strong>Design: </strong>Danish nationwide active comparator study.</p><p><strong>Setting: </strong>National Danish registries, 1 January 2000 to 31 December 2022.</p><p><strong>Participants: </strong>1 29 254 individuals with dementia were matched by age and sex to 646 270 controls without dementia, identified from a cohort of 2.26 million individuals aged 60-75 years between 2000 and 2022 with no previous dementia. Two separate nested case-control populations were studied: the general population and an active comparator population of 58 242 new users of bladder drugs (2198 developed dementia and were matched to 10 990 controls). Information on medication use was based on filled prescriptions and defined daily doses.</p><p><strong>Main outcome measures: </strong>Conditional logistic regression provided incidence rate ratios for associations between anticholinergic bladder drugs and dementia compared with non-use and mirabegron use adjusted for educational level, cardiovascular disease, diabetes, hypertension, dyslipidaemia, and Charlson Comorbidity Index.</p><p><strong>Results: </strong>Compared with non-use, ever use of anticholinergic bladder drugs was associated with an increased risk of dementia, with an incidence rate ratio of 1.44 (95% confidence interval (CI) 1.40 to 1.48). The incidence rate ratio increased with increasing cumulative drug use, from 1.31 (95% CI 1.27 to 1.36) for 1-90 defined daily doses to 1.68 (1.59 to 1.76) for >365 defined daily doses. Compared with non-use, all types of anticholinergic bladder drugs were associated with increased incidence rate ratios for dementia: tolterodine 1.43 (95% CI 1.38 to 1.49), solifenacin 1.37 (1.29 to 1.46), trospium 1.52 (1.37 to 1.67), and fesoterodine 1.48 (1.26 to 1.74). The increased risk of dementia with use of anticholinergic bladder drugs was not seen when compared directly with the use of the β3 agonist mirabegron (incidence rate ratio 0.82, 95% CI 0.74 to 0.92), irrespective of the type of anticholinergic drug.</p><p><strong>Conclusions: </strong>In this study, all types of anticholinergic bladder drugs were associated with an increased risk of dementia compared with non-use, but not when applying the active comparator of the β3 agonist bladder drug mirabegron. These findings highlight the relevance of using an active comparator. Future research should evaluate the risk of cognitive impairment and dementia for both types of bladder drugs.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"4 1","pages":"e001125"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}