BMJ medicine最新文献

{"title":"Polycystic ovary syndrome: pathophysiology and therapeutic opportunities.","authors":"Jiawen Dong, D Aled Rees","doi":"10.1136/bmjmed-2023-000548","DOIUrl":"10.1136/bmjmed-2023-000548","url":null,"abstract":"<p><p>Polycystic ovary syndrome is characterised by excessive levels of androgens and ovulatory dysfunction, and is a common endocrine disorder in women of reproductive age. Polycystic ovary syndrome arises as a result of polygenic susceptibility in combination with environmental influences that might include epigenetic alterations and in utero programming. In addition to the well recognised clinical manifestations of hyperandrogenism and ovulatory dysfunction, women with polycystic ovary syndrome have an increased risk of adverse mental health outcomes, pregnancy complications, and cardiometabolic disease. Unlicensed treatments have limited efficacy, mostly because drug development has been hampered by an incomplete understanding of the underlying pathophysiological processes. Advances in genetics, metabolomics, and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine, and steroidogenic pathways, including increased gonadotrophin releasing hormone pulsatility, androgen excess, insulin resistance, and changes in the gut microbiome. Many patients with polycystic ovary syndrome have high levels of 11-oxygenated androgens, with high androgenic potency, that might mediate metabolic risk. These advances have prompted the development of new treatments, including those that target the neurokinin-kisspeptin axis upstream of gonadotrophin releasing hormone, with the potential to lessen adverse clinical sequelae and improve patient outcomes.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000548"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/5b/bmjmed-2023-000548.PMC10583117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685694","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":"Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM.","authors":"Rohan Khera, Lovedeep Singh Dhingra, Arya Aminorroaya, Kelly Li, Jin J Zhou, Faaizah Arshad, Clair Blacketer, Mary G Bowring, Fan Bu, Michael Cook, David A Dorr, Talita Duarte-Salles, Scott L DuVall, Thomas Falconer, Tina E French, Elizabeth E Hanchrow, Scott Horban, Wallis Cy Lau, Jing Li, Yuntian Liu, Yuan Lu, Kenneth Kc Man, Michael E Matheny, Nestoras Mathioudakis, Michael F McLemore, Evan Minty, Daniel R Morales, Paul Nagy, Akihiko Nishimura, Anna Ostropolets, Andrea Pistillo, Jose D Posada, Nicole Pratt, Carlen Reyes, Joseph S Ross, Sarah Seager, Nigam Shah, Katherine Simon, Eric Yf Wan, Jianxiao Yang, Can Yin, Seng Chan You, Martijn J Schuemie, Patrick B Ryan, George Hripcsak, Harlan Krumholz, Marc A Suchard","doi":"10.1136/bmjmed-2023-000651","DOIUrl":"10.1136/bmjmed-2023-000651","url":null,"abstract":"<p><strong>Objective: </strong>To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.</p><p><strong>Design: </strong>Federated pharmacoepidemiological evaluation in LEGEND-T2DM.</p><p><strong>Setting: </strong>10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.</p><p><strong>Participants: </strong>4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.</p><p><strong>Exposure: </strong>The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.</p><p><strong>Main outcomes measures: </strong>The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.</p><p><strong>Results: </strong>4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.</p><p><strong>Conclusions: </strong>Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000651"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/09/bmjmed-2023-000651.PMC10565313.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41221741","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":"Effect of national guidance on survival for babies born at 22 weeks’ gestation in England and Wales: population based cohort study","authors":"Lucy K Smith, Emily van Blankenstein, Grenville Fox, Sarah E Seaton, Mario Martínez-Jiménez, Stavros Petrou, Cheryl Battersby","doi":"10.1136/bmjmed-2023-000579","DOIUrl":"https://doi.org/10.1136/bmjmed-2023-000579","url":null,"abstract":"Objectives To explore the effect of changes in national clinical recommendations in 2019 that extended provision of survival focused care to babies born at 22 weeks’ gestation in England and Wales. Design Population based cohort study. Setting England and Wales, comprising routine data for births and hospital records. Participants Babies alive at the onset of care in labour at 22 weeks+0 days to 22 weeks+6 days and at 23 weeks+0 days to 24 weeks+6 days for comparison purposes between 1 January 2018 and 31 December 2021. Main outcome measures Percentage of babies given survival focused care (active respiratory support after birth), admitted to neonatal care, and surviving to discharge in 2018-19 and 2020-21. Results For the 1001 babies alive at the onset of labour at 22 weeks' gestation, a threefold increase was noted in: survival focused care provision from 11.3% to 38.4% (risk ratio 3.41 (95% confidence interval 2.61 to 4.45)); admissions to neonatal units from 7.4% to 28.1% (3.77 (2.70 to 5.27)), and survival to discharge from neonatal care from 2.5% to 8.2% (3.29 (1.78 to 6.09)). More babies of lower birth weight and early gestational age received survival focused care in 2020-21 than 2018-19 (46% to 64% at <500g weight; 19% to 31% at 22 weeks+0 days to 22 weeks+3 days). Conclusions A change in national guidance to recommend a risk based approach was associated with a threefold increase in 22 weeks’ gestation babies receiving survival focused care. The number of babies being admitted to neonatal units and those surviving to discharge increased.","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"127 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136199165","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":"Quality of reporting of adverse events in clinical trials of covid-19 drugs: systematic review.","authors":"Karima Madi,&nbsp;Clara Flumian,&nbsp;Pascale Olivier,&nbsp;Agnès Sommet,&nbsp;François Montastruc","doi":"10.1136/bmjmed-2022-000352","DOIUrl":"https://doi.org/10.1136/bmjmed-2022-000352","url":null,"abstract":"Objective To assess the quality of reporting of adverse events in clinical trials of covid-19 drugs based on the CONSORT (Consolidated Standards of Reporting Trials) harms extension and according to clinical trial design, and to examine reporting of serious adverse events in drug trials published on PubMed versus clinical trial summaries on ClinicalTrials.gov. Design Systematic review. Data sources PubMed and ClinicalTrials.gov registries were searched from 1 December 2019 to 17 February 2022. Eligibility criteria for selecting studies Randomised clinical trials evaluating the efficacy and safety of drugs used to treat covid-19 disease in participants of all ages with suspected, probable, or confirmed SARS-CoV-2 infection were included. Clinical trials were screened on title, abstract, and text by two authors independently. Only articles published in French and English were selected. The Cochrane risk of bias tool for randomised trials (RoB 2) was used to assess risk of bias. Results The search strategy identified 1962 randomised clinical trials assessing the efficacy and safety of drugs used to treat covid-19, published in the PubMed database; 1906 articles were excluded after screening and 56 clinical trials were included in the review. Among the 56 clinical trials, no study had a high score for quality of reporting of adverse events, 60.7% had a moderate score, 33.9% had a low score, and 5.4% had a very low score. All clinical trials with a very low score for quality of reporting of adverse events were randomised open label trials. For reporting of serious adverse events, journal articles published on PubMed under-reported 51% of serious adverse events compared with clinical trial summaries published on ClinicalTrials.gov. Conclusions In one in three published clinical trials on covid-19 drugs, the quality of reporting of adverse events was low or very low. Differences were found in the number of serious adverse events reported in journal articles versus clinical trial summaries. During the covid-19 pandemic, risk assessment of drugs in clinical trials of covid-19 drugs did not comply with good practice recommendations for publication of results. Systematic review registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) EUPAS45959.","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000352"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/02/bmjmed-2022-000352.PMC10537984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124522","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":"Transparent reporting of adaptive clinical trials using concurrently randomised cohorts.","authors":"Ian C Marschner, Mark Jones, James A Totterdell, Robert K Mahar, Thomas L Snelling, Steven Y C Tong","doi":"10.1136/bmjmed-2023-000497","DOIUrl":"10.1136/bmjmed-2023-000497","url":null,"abstract":"<p><p>Adaptive clinical trials have designs that evolve over time because of changes to treatments or changes to the chance that participants will receive these treatments. These changes might introduce confounding that biases crude comparisons of the treatment arms and makes the results from standard reporting methods difficult to interpret for adaptive trials. To deal with this shortcoming, a reporting framework for adaptive trials was developed based on concurrently randomised cohort reporting. A concurrently randomised cohort is a subgroup of participants who all had the same treatments available and the same chance of receiving these treatments. The reporting of pre-randomisation characteristics and post-randomisation outcomes for each concurrently randomised cohort in the study is recommended. This approach provides a transparent and unbiased display of the degree of baseline balance and the randomised treatment comparisons for adaptive trials. The key concepts, terminology, and recommendations underlying concurrently randomised cohort reporting are presented, and its routine use in adaptive trial reporting is advocated.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000497"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/d4/bmjmed-2023-000497.PMC10510920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175421","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":"Preconception contraceptive use and miscarriage: prospective cohort study.","authors":"Jennifer J Yland, Amelia K Wesselink, Sonia Hernandez-Diaz, Krista Huybrechts, Elizabeth E Hatch, Tanran R Wang, David Savitz, Wendy Kuohung, Kenneth J Rothman, Lauren A Wise","doi":"10.1136/bmjmed-2023-000569","DOIUrl":"10.1136/bmjmed-2023-000569","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the association between preconception contraceptive use and miscarriage.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting: </strong>Residents of the United States of America or Canada, recruited from 2013 until the end of 2022.</p><p><strong>Participants: </strong>13 460 female identified participants aged 21-45 years who were planning a pregnancy were included, of whom 8899 conceived. Participants reported data for contraceptive history, early pregnancy, miscarriage, and potential confounders during preconception and pregnancy.</p><p><strong>Main outcome measure: </strong>Miscarriage, defined as pregnancy loss before 20 weeks of gestation.</p><p><strong>Results: </strong>Preconception use of combined and progestin-only oral contraceptives, hormonal intrauterine devices, copper intrauterine devices, rings, implants, or natural methods was not associated with miscarriage compared with use of barrier methods. Participants who most recently used patch (incidence rate ratios 1.34 (95% confidence interval 0.81 to 2.21)) or injectable contraceptives (1.44 (0.99 to 2.12)) had higher rates of miscarriage compared with recent users of barrier methods, although results were imprecise due to the small numbers of participants who used patch and injectable contraceptives.</p><p><strong>Conclusions: </strong>Use of most contraceptives before conception was not appreciably associated with miscarriage rate. Individuals who used patch and injectable contraceptives had higher rates of miscarriage relative to users of barrier methods, although these results were imprecise and residual confounding was possible.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000569"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/d0/bmjmed-2023-000569.PMC10496668.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626432","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":"Stop smoking, keep walking, . . . and other stories","authors":"","doi":"10.1136/bmj.p1993","DOIUrl":"https://doi.org/10.1136/bmj.p1993","url":null,"abstract":"The human genome encodes approximately 20 000 proteins. Understandably enough, investigations have concentrated on genes and proteins whose function is known.However, thehuman “unknome,” the one fifth of humangeneswhosepurpose remains mysterious, shouldn’t be ignored. Many of these genes are conserved across species. In experiments with fruit flies, removing one of these mystery genes caused the insects to die. The compilers of a new database of genes with unknown functions hope it will widen the focus of genetic research (PLoS Biol doi:10.1371/journal.pbio.3002222).","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80405852","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":"A persistent sore throat","authors":"Takanori Yamaguchi, Kei Suzuki","doi":"10.1136/bmj-2023-074870","DOIUrl":"https://doi.org/10.1136/bmj-2023-074870","url":null,"abstract":"Takanori Yamaguchi, Kei Suzuki This man in his 30s had a sore throat for two months and was initially thought to have viral pharyngitis. He then developed fever and enlarged, painful cervical lymph nodes. On examination, white patches were visible on the soft palate (fig 1). Biopsy of these patches excluded malignancy. Results from serum Treponema pallidumhaemagglutination and rapidplasma reagin (RPR) testswere positive (RPR: 120units) and secondary syphilis was diagnosed. Antibody test results for HIV-1 and 2 were negative. The man had condomless sex and mutual oral sex with a sex worker three months before presentation. He had no other sexual partners and no history of sexually transmitted diseases.","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76140091","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":"NSAIDs and contraceptives: critical thinking on a harmful drug interaction","authors":"K. Abbasi","doi":"10.1136/bmj.p2041","DOIUrl":"https://doi.org/10.1136/bmj.p2041","url":null,"abstract":"As an early career doctor I prescribed diclofenac liberally. It was my go-to anti-inflammatory drug for patients in hospital. My prescribing habit wasn’t influenced by evidence but by learnt behaviour. It was the drug others prescribed. Ibuprofen was one of the other options, and during my stint in rheumatology a consultant hadwarnedmeof people taking ibuprofen “like smarties” but being unaware of the risk of renal failure. If not ibuprofen, then diclofenac, or another non-steroidal anti-inflammatory drug. Perhaps the evidencewasn’t then clear about the effects of prescribing NSAIDs to women using hormonal contraception? Perhaps I should have paid more attention? Perhaps I would have been better served by critical appraisal and knowledge synthesis and translation, skills I had barely acquired?","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78439850","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":"Advances in the management of type 2 diabetes in adults.","authors":"Rodolfo J Galindo, Jennifer M Trujillo, Cecilia C Low Wang, Rozalina G McCoy","doi":"10.1136/bmjmed-2022-000372","DOIUrl":"10.1136/bmjmed-2022-000372","url":null,"abstract":"<p><p>Type 2 diabetes is a chronic and progressive cardiometabolic disorder that affects more than 10% of adults worldwide and is a major cause of morbidity, mortality, disability, and high costs. Over the past decade, the pattern of management of diabetes has shifted from a predominantly glucose centric approach, focused on lowering levels of haemoglobin A_1c (HbA_1c), to a directed complications centric approach, aimed at preventing short term and long term complications of diabetes, and a pathogenesis centric approach, which looks at the underlying metabolic dysfunction of excess adiposity that both causes and complicates the management of diabetes. In this review, we discuss the latest advances in patient centred care for type 2 diabetes, focusing on drug and non-drug approaches to reducing the risks of complications of diabetes in adults. We also discuss the effects of social determinants of health on the management of diabetes, particularly as they affect the treatment of hyperglycaemia in type 2 diabetes.</p>","PeriodicalId":72433,"journal":{"name":"BMJ medicine","volume":"2 1","pages":"e000372"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/3c/bmjmed-2022-000372.PMC10481754.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186511","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}