BMC Medicine最新文献

{"title":"A systematic review and network meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from randomised controlled trials of immunomodulatory therapies.","authors":"Sophie E Beese, Malcolm J Price, Claire Tomlinson, Pawana Sharma, Isobel M Harris, Ada Adriano, Lauren M Quinn, Ritu Gada, Thomas J Horgan, Fiona Maggs, Martin Burrows, Krishnarajah Nirantharakumar, G Neil Thomas, Robert C Andrews, David J Moore, Parth Narendran","doi":"10.1186/s12916-025-04201-z","DOIUrl":"10.1186/s12916-025-04201-z","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes is characterised by the immune-mediated destruction of pancreatic beta cells. We aimed to determine the effectiveness of immunotherapies for preserving residual beta cell function in newly diagnosed (stage 3) type 1 diabetes.</p><p><strong>Methods: </strong>Searches were carried out in MEDLINE, Embase, Cochrane CENTRAL and trial registries until 31st Jul 2024. RCTs of immunotherapies to preserve beta cells in newly diagnosed type 1 diabetes were included. Data were extracted using a bespoke, piloted extraction sheet. Risk of bias was assessed using Cochrane Risk of Bias Tool 1. A random effects network meta-analysis was undertaken in R. The primary outcome was C-peptide. Interventions were analysed by class.</p><p><strong>Results: </strong>Sixty trials were included (4597 patients, 32 intervention classes). Forty-one trials of 42 interventions were eligible for network meta-analysis. Eleven interventions demonstrated statistically significantly higher levels of C-peptide than placebo at 12 months, mesenchymal stem cells (autologous and Wharton's jelly-derived cells), azathioprine, interferon-alpha (5000 IU), autologous dendritic cells, anti-TNF golimumab, low-dose ATG, 3 mg 1-course anti-CD3 teplizumab, baricitinib, cyclosporin and 9/11 mg 2-course anti-CD3 teplizumab but with substantial heterogeneity present (I² = 66%). Azathioprine ranked highest (median ranking 3rd); however, rankings demonstrated relatively wide confidence intervals and thus uncertainty in exact rank order of near adjacent therapies. Risk of bias assessment identified poor reporting, particularly in older trials, but few studies demonstrated high risk overall.</p><p><strong>Conclusions: </strong>Eleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity.</p><p><strong>Systematic review registration: </strong>The protocol for the systematic review was registered on PROSPERO, the international database of prospectively registered systematic reviews (registration: CRD42018107904).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"351"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538814","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 genetic spectrum features of 2261 Chinese children with epilepsy and intellectual disability.","authors":"Nan Pang, Chen Chen, Lifen Yang, Ciliu Zhang, Xiaolu Deng, Li Yang, Leilei Mao, Fangyun Liu, Guoli Wang, Haolin Duan, Xiaole Wang, Fei Yin, Fang He, Jing Peng","doi":"10.1186/s12916-025-04220-w","DOIUrl":"10.1186/s12916-025-04220-w","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy (EP) and intellectual disability (ID) are two highly correlated diseases that seriously impact neurodevelopment in children. Precision diagnosis of EP and ID remains challenging due to their clinical and genetic heterogeneity, necessitating a profound understanding of disease characteristics.</p><p><strong>Methods: </strong>We provide a clinical and genetic landscape of 2261 Chinese patients performed chromosome microarray analysis (CMA) or next-generation sequencing to uncover causal copy number variants (CNVs) or single-nucleotide variants (SNVs). Patients were stratified into three groups: EP (374 cases), ID (863 cases), and EP + ID (1024 cases).</p><p><strong>Results: </strong>We reported a 24.3% diagnostic yield from 496 causal CNVs and SNVs, including 182 novel variants, in which updated 33 previously reported VUS. Significant intergroup differences emerged: EP patients were predominantly caused by autosomal dominant SNVs, showing the highest rates of incomplete penetrance and family history. ID patients were more likely caused by CNVs and autosomal recessive SNVs, with the highest genetic heterogeneity. EP + ID patients displayed the earliest onset ages and highest diagnostic yields. We prioritized genes by diagnostic efficiency and revealed that X-linked SNVs disproportionately affected females, particularly in the EP + ID group, under current diagnostic paradigms. This real-world dataset informs genetic counseling, testing strategies, precision therapies, and long-term management for EP/ID.</p><p><strong>Conclusions: </strong>The clinical and genetic profiles from this study provided a reliable baseline reference for diagnosing EP and ID.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"388"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538900","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":"Smoking cessation for people accessing homeless support centres (SCeTCH): comparing the provision of an e-cigarette versus usual care in a cluster randomised controlled trial in Great Britain.","authors":"Lynne Dawkins, Kirstie Soar, Francesca Pesola, Allison Ford, Caitlin Notley, Rachel Brown, Emma Ward, Lauren McMillan, Debbie Robson, Anna Varley, Charlotte Mair, Jessica Lennon, Janine Brierley, Amy Edwards, Peter Hajek, Allan Tyler, Steve Parrott, Jinshuo Li, Linda Bauld, Bethany Gardner, Sharon Cox","doi":"10.1186/s12916-025-04167-y","DOIUrl":"10.1186/s12916-025-04167-y","url":null,"abstract":"<p><strong>Background: </strong>Smoking rates are exceptionally high among people experiencing homelessness. We aimed to test the effectiveness of an e-cigarette (EC) intervention designed to help people accessing homeless support services to stop smoking.</p><p><strong>Methods: </strong>A two-arm cluster randomised controlled trial. We recruited 32 homeless centres (clusters) across Great Britain. Participants were aged 18 + and known by centre staff to smoke. Randomisation of clusters (1:1; using various block sizes) to EC or usual care (UC) was generated in Stata by the trial statistician, concealed from researchers. Participants in EC clusters received a refillable EC, 4-week supply of e-liquid, and a fact sheet. UC participants received very brief advice on smoking, a support leaflet, and signposting to the stop smoking service. Interventions were delivered by centre staff. The primary outcome was sustained abstinence from smoking from 2 weeks post-baseline through to 24 weeks, verified by carbon monoxide (CO) measurements below 8 ppm. Secondary outcomes included CO-verified 7-day point prevalence abstinence. Analysis was intention-to-treat.</p><p><strong>Results: </strong>Between February 22, 2022, and June 22, 2023, 16 centres were randomised to EC (n = 239 participants) and 16 to UC (n = 238 participants). In UC, one participant died, and one withdrew consent. Final sample analysed: n = 239 (EC); n = 236 (UC). Sustained 24-week CO-validated smoking cessation rates were 5/239 (2.1%) with EC vs. 2/236 (0.8%) with UC (aRR: 2.43, 95%CI: 0.51-11.64). Seven-point prevalence abstinence was 15/239 (6.3%) in the EC arm vs. 5/236 (2.1%) in UC (aRR: 2.95, 95%CI: 1.05-8.29). Four adverse events were reported in the EC arm; three deemed EC-related and not serious; one serious and not EC-related.</p><p><strong>Conclusions: </strong>EC did not support sustained smoking abstinence for 24 weeks. Seven-day point prevalence abstinence rates suggest that cessation is possible, but more support may be needed to sustain this.</p><p><strong>Trial registration: </strong>The trial was preregistered on the ISTCTN registry #18566874. Registration date: 12/10/2021.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"394"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538896","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":"Differential effects of inulin and fructooligosaccharides on gut microbiota composition and glycemic metabolism in overweight/obese and healthy individuals: a randomized, double-blind clinical trial.","authors":"Jie Li, Feitong Liu, Yuemei Luo, Anisha Wijeyesekera, Shan Wang, Xiaojiao Chen, Yamei Lv, Jing Jin, Huafang Sheng, Guopan Wang, Yuanan Wei, Zhuang Li, Muxuan Chen, Hongwei Zhou","doi":"10.1186/s12916-025-04189-6","DOIUrl":"10.1186/s12916-025-04189-6","url":null,"abstract":"<p><strong>Background: </strong>Modulating the gut microbiota with prebiotics is a promising strategy for managing metabolic diseases. However, the clinical effects on glycemic metabolism across different populations remain uncertain. In this study, we conducted a randomized, double-blind investigation to examine the impact of inulin and fructooligosaccharides (FOS) on glycemic metabolism in overweight/obese and healthy adults.</p><p><strong>Methods: </strong>A total of 131 adults were included, with 44 receiving inulin, 43 receiving FOS, and 44 receiving placebo over a period of 4 weeks. Blood and fecal samples were collected before and after the intervention, and various metabolic parameters, gut microbiota composition, and metabolites were analyzed.</p><p><strong>Results: </strong>Placebo had no effect on glycemic metabolism or gut microbiota. Inulin significantly reduced glucose levels at 1 h (Cohen's d = 0.71, p = 0.041) and 2 h (Cohen's d = 0.73, p = 0.028) during oral glucose tolerance test (OGTT), increased fasting insulin (Cohen's d = 0.70, p = 0.008), and lowered homocysteine (HCY) levels (Cohen's d = 0.76, p = 0.014) in overweight/obese individuals. These effects were not observed in healthy individuals. In contrast, although FOS significantly decreased HCY (Cohen's d = 0.72, p = 0.023), it did not improve glycemic metrics in either group. Inulin also reduced the abundance of Ruminococcus by 72.0% (from 1.661% ± 1.501% to 0.465% ± 0.594%), positively correlating with improved glycemic outcomes. Propionate levels decreased significantly in both overweight/obese (Cohen's d = 0.89, p = 0.014) and healthy participants (Cohen's d = 1.19, p = 0.020) following inulin. Functional prediction of gut microbiota revealed upregulation of microbial folate and glutathione metabolism with inulin, and purine metabolism with FOS.</p><p><strong>Conclusions: </strong>Practically, inulin may be more suitable for managing glycemic dysregulation in overweight or obese individuals, while FOS may be considered for HCY reduction in individuals with normal glycemic status. Such targeted use of prebiotics could complement existing dietary and pharmacologic strategies in personalized metabolic care.</p><p><strong>Trial registration number: </strong>ChiCTR-IOR-17010574.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"372"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538843","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":"Single low dose primaquine to block the transmission of Plasmodium falciparum-proposed stand-alone and ACT-adapted regimens.","authors":"Walter R J Taylor, Peter Olupot-Olupot, Marie A Onyamboko, Natenapa Chimjinda, Chiraporn Taya, Julie Nguyen Ngoc Pouplin, Thomas N Williams, Kathryn Maitland, Caterina A Fanello, Nicholas P J Day, Joel Tarning, Nicholas J White, Mavuto Mukaka","doi":"10.1186/s12916-025-04153-4","DOIUrl":"10.1186/s12916-025-04153-4","url":null,"abstract":"<p><strong>Background: </strong>Despite the 2012 WHO recommendation to add single low dose primaquine (SLDPQ, 0.25 mg/kg body weight) to artemisinin-based combination treatments (ACTs) for blocking the transmission of artemisinin-resistant Plasmodium falciparum, there are currently no weight-based regimens founded on robust evidence.</p><p><strong>Methods: </strong>Applying published safety, transmission blocking and pharmacokinetic data, and exploring pharmacokinetic-pharmacodynamic relationships of age-based dosing of SLDPQ in African children with acute, uncomplicated Plasmodium falciparum, we derived weight-based, stand-alone, ACT-, triple ACT-, and vivax-matched regimens by following allometric dosing principles and simulating PQ exposure (area under the concentration time curve). The ACTs were dihydroartemisinin piperaquine (DHAPP), artesunate pyronaridine (ASPYR), artesunate amodiaquine (ASAQ), artesunate mefloquine (ASMQ), artemether lumefantrine (AL), and ALAQ. Tablet strengths were predefined: 2.5, 3.75, 5, 7.5, and 15 mg, and no tablet fractions were allowed. The maximum mg/kg dose was set at 0.5, and, primarily for ease of ACT co-blistering, 1 tablet = 1 dose. We assessed different mg/kg doses and selected the dosing associated with a predicted median exposure closest to 1200 ng*h/mL, the exposure predicted for a 60 kg individual given 15 mg of PQ.</p><p><strong>Results: </strong>The designed 8 regimens had 4-8 dosing bands. The stand-alone, DHAPP, and ASPYR regimens contain the full line of PQ tablets and all other regimens, except AL (2.5, 7.5, 15 mg) and ALAQ (2.5, 5, 7.5, 15 mg), use 3.75 mg. The 2.5 mg tablet resulted in a maximum dose of 0.56 mg/kg for ASAQ, as this regimen starts at 4.5 kg body weight, whilst all other regimens start at 5 kg and resulted in 0.5 mg/kg. Substituting 3.75 mg with 5 mg results in maximum doses of 0.56 mg/kg (ASAQ, ASMQ) and 0.63 mg/kg (other regimens), risking greater toxicity. Across all dosing bands, 0.17 - 0.56 mg/kg doses predict exposures of ~ 500 - 2000 ng*mL/h. Regimens with more dosing bands had less variations in exposure.</p><p><strong>Conclusions: </strong>These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to co-blister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg tablet for prequalification and determine which regimens should be incorporated into their treatment guidelines to advance malaria elimination.</p><p><strong>Trial registration: </strong>The trial is registered at ISRCTN, number 11594437.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"397"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538895","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":"Impact of kindergarten structures on the dynamics of hand, foot, and mouth disease and the effects of intervention strategies: an agent-based modeling study.","authors":"Qing Zou, Xin-Fu Shi, Chang-Wei Liang, Meng-Meng Ma, Jing-Hua Li, Jing Gu, Ying-Si Lai","doi":"10.1186/s12916-025-04207-7","DOIUrl":"10.1186/s12916-025-04207-7","url":null,"abstract":"<p><strong>Background: </strong>Hand, foot, and mouth disease (HFMD) poses an unignorable threat to the health of kindergarten children. Kindergarten structures (i.e., class size and kindergarten size) may influence the transmission dynamics and the effectiveness of non-pharmaceutical interventions (NPIs), but few studies have explored these effects.</p><p><strong>Methods: </strong>We developed an agent-based network model to study the effects of kindergarten structures on dynamics of HFMD caused by three types of strains (i.e., EV-A71, CVA16, and other EVs). We pursued a systematic review to collect data on HFMD outbreaks to estimate key model parameters. We simulated a series of scenarios to study the effects of NPIs (i.e., isolation of symptomatic individuals, class and family quarantine, and kindergarten closure, organized stepwisely), under different kindergarten sizes (n = 180, 360, and 900) and class sizes (m = 10, 20, 30, 60, etc.). We further explored alternative interventions combined with vaccination to avoid kindergarten closure during an outbreak.</p><p><strong>Results: </strong>Overall, we found that the larger the class size, the more cumulative infections and the less effectiveness of NPIs in kindergartens. Stronger NPIs resulted in better effectiveness, and the variations in effectiveness among different class sizes gradually reduced with stronger interventions. Similar patterns were shown in kindergartens with small, medium, and large sizes. NPIs including kindergarten closure, which is implemented in many endemic countries, was a potent epidemic control strategy, capable of reducing cumulative incidence by over 80% for most class sizes in medium-size kindergartens. For EV-A71 infections, a vaccine coverage of 50% was alternative to kindergarten closure, when class size was 60 or less in medium-size kindergartens.</p><p><strong>Conclusions: </strong>Kindergarten structures, particularly class size, had an important impact on dynamics of HFMD and effectiveness of NPIs within kindergarten. Increasing vaccination coverage may be an alternative to kindergarten closure for control of the disease.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"357"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538862","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":"Policy implementation and recommendations to address the double burden of malnutrition in South Africa: expert assessment using the expanded Healthy Food Environment Policy Index (Food-EPI).","authors":"Nicole Holliday, Peter Delobelle, Carmen Klinger, Zandile June-Rose Mchiza, Olufunke Alaba, Stefanie Vandevijvere, Peter von Philipsborn, Karin Geffert","doi":"10.1186/s12916-025-04191-y","DOIUrl":"10.1186/s12916-025-04191-y","url":null,"abstract":"<p><strong>Background: </strong>South Africa faces a double burden of malnutrition (DBM), the coexistence and interaction of multiple forms of malnutrition (undernutrition, micronutrient deficiencies, and overweight/obesity) within individuals and households and across the life course. A healthy food environment is necessary to reduce this DBM. The Healthy Food Environment Policy Index (Food-EPI) can be used to evaluate the implementation of public nutrition and food environment policies in comparison with international best practices. The aim of this study was to assess the extent of implementation of healthy food environment policies in South Africa using an expanded DBM Food-EPI framework, benchmark policies against international best practices, develop priority policy recommendations, and compare implementation progress since the 2016 South African Food-EPI assessment.</p><p><strong>Methods: </strong>From October 2023 to March 2024, a panel of 23 national experts from different tiers of government (Department of Health), academia, and civil society was invited to participate in the Food-EPI assessment. Through two workshops and online feedback, experts evaluated the implementation of food environment policies across 60 indicators, compared these policies to international best practices, and proposed and prioritized a list of policy actions based on perceived implementation gaps.</p><p><strong>Results: </strong>Of the 23 invited experts, 13 participated in the benchmarking workshop in which about 70% of indicators were rated at very low to low levels of implementation. Overall, of the 48 original indicators, the mean level of implementation improved from 2016 to 2024. Of the 12 indicators that addressed the DBM, eight were rated at very low to low levels of implementation. The experts (original panel plus four additional participants) then proposed ten priority actions, mainly across the domains of Food Promotion, Food Prices, Funding, and Platforms for Interaction.</p><p><strong>Conclusions: </strong>Application of the expanded Food-EPI in South Africa showed improvements for the original indicators compared with 2016 and highlights the need for additional policy efforts to improve public nutrition policy and address the DBM.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"360"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538888","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":"Prevalence and attributes of cervicovaginal human papillomavirus infection among a 35-year- age- cohort of ever-married women in a district of Sri Lanka: a cross-sectional study.","authors":"K C M Perera, N Mapitigama, H T C S Abeysena","doi":"10.1186/s12916-025-04246-0","DOIUrl":"10.1186/s12916-025-04246-0","url":null,"abstract":"<p><strong>Background: </strong>All cervical cancers are virtually associated with sexually transmitted cervicovaginal human papillomavirus (HPV) infection. The objective of the study was to determine the prevalence and risk factors of cervicovaginal Human Papillomavirus infection among a 35-year-old-age cohort of ever-married women in Kalutara district.</p><p><strong>Methods: </strong>A community-based descriptive cross-sectional study was conducted from 1st of July 2018 to 30th November 2018 among ever-married women 35 years of age in Kalutara district. Three women from each cluster (n = 413) were selected by consecutive sampling technique. HPV/DNA cervical specimen collection (n = 822) was carried out. Cervical specimens were tested by well-trained cyto-screeners with cobas 4800 HPV/DNA automated Polymerase Chain Reaction (PCR) machine. An Interviewer-administered questionnaire was used to gather information regarding socio-demographics, reproductive health, contraceptive methods, and sexual behaviours. Multivariate logistic regression was performed and expressed as odds ratio (OR) and 95% confidence interval (CI).</p><p><strong>Results: </strong>The prevalence of HPV infection was 6.2% (95% CI: 6.18%-6.22%), while the prevalence of high-risk genotypes 16 and 18 was 1.94% (95% CI: 1.93%-1.95%). The prevalence of 12 pooled high-risk HPV infection was 4.14% (95% CI:4.13%-4.15%). In multivariate logistic regression analysis, age at marriage ≤ 24 years (OR = 4.04, 95% CI:1.75-9.34), any abortion including both induced and miscarriages (OR = 10.1, 95% CI: 3.07-33.7), use of hormonal contraceptives for ≥ 3 months (OR = 45.5, 95% CI: 18.7-110.5) and a number of vaginal deliveries > 2 (OR = 9.7, 95% CI: 3.7-25.2) were found to have a significant risk association with HPV infection, while average monthly income > Rs. 15,000 (OR = 0.12, 95% CI, 0.04-0.32) and ever use of a condom by a spouse (OR = 0.04, 95% CI: 0.01-0.16) were found to have a significant protective association with HPV infection.</p><p><strong>Conclusions: </strong>Exposure to HPV infection is determined by risk factors such as early marriage, any abortions, prolonged usage of hormonal contraceptives, and high number of vaginal deliveries. Strengthening behaviour change communication to alleviate underlying risk factors and to promote prevention is very important.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"358"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538891","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":"Early weaning from oxygen therapy in African children with severe pneumonia.","authors":"Kathryn Maitland, Elisa Giallongo, Mainga Hamaluba, Florence Alaroker, Robert O Opoka, Abner Tagoola, Damalie Nalwanga, Eva Nabawanuka, William Okiror, Margaret Nakuya, Denis Aromut, Thomas N Williams, Karen Thomas, David A Harrison, Paul Mouncey, Andrew Bush, J F Fraser, Kathy Rowan, Peter Olupot-Olupot, Sarah Kiguli","doi":"10.1186/s12916-025-04178-9","DOIUrl":"10.1186/s12916-025-04178-9","url":null,"abstract":"<p><strong>Background: </strong>In Africa, severe pneumonia remains the major cause of paediatric hospitalisation, resulting in high requirements for oxygen therapy. Adequate supplies of oxygen are key challenges for many low-resource hospitals. The World Health Organization manual for oxygen therapy advises 2-3 days of oxygen therapy for pneumonia and recommends against early weaning, even in the absence of hypoxaemia. Few data support this recommendation. We describe the oxygen use and timing of weaning in the COAST trial of oxygen therapy (ISRCTN15622505).</p><p><strong>Methods: </strong>Children aged 28 days to 12 years presenting to 6 hospitals in Uganda and Kenya with severe pneumonia and hypoxaemia (saturations < 92% on pulse oximetry (SpO₂) were eligible for the trial. Children in two strata (a) severe hypoxaemia (SpO₂ < 80%) and (b) moderate hypoxaemia (SpO₂ 80-91%) were allocated to receive high flow nasal therapy (HFNT), low flow oxygen delivery (LFO) or control (no immediate oxygen (moderate hypoxaemia stratum only)). Children were closely monitored over 48 h by pulse oximetry and weaned off oxygen once SpO₂ > 92%. We describe the oxygen use and proportion requiring respiratory support over time by intervention strategy.</p><p><strong>Results: </strong>Of the 1842 children enroled the majority, 1454 (79%) had moderate hypoxaemia. In this stratum, by 2 and 8 h, 148 (41%) and 200/360 (55.6%) in the LFO arm had been weaned; in the HFNT arm, 213/362 (59%) were receiving respiratory support at 2 h in room alone, and by 8 h, 164/362 (45%) had been weaned. At 48 h, in the respective strata, 77-80% and 53-63% still had respiratory distress but without hypoxaemia and were thus not receiving oxygen. Median oxygen use at 48 h in the moderate hypoxaemia group was highest in LFO am 480L (IQR 236.2, 2132.2) compared to 113.4 L (IQR 0.0, 1453.9) in the HFNT and 0 L (IQR 0.0) in the control arms. Children requiring oxygen beyond 48 h, 17/33 (51.1%) and 9/46 (19.5%) in the respective strata, had additional cardiac conditions.</p><p><strong>Conclusions: </strong>Closely monitoring SpO₂ resulted in early weaning and reduced the use of and exposure to oxygen. Where oxygen supplies are at a premium, this approach may improve equitable access for children with severe pneumonia.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"366"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538845","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":"Long-term efficacy and updated survival outcomes of sintilimab plus anlotinib in patients with PD-L1-positive recurrent or metastatic cervical cancer.","authors":"Jing Liu, Chunyan Lan, Tongyu Liu, Qin Liu, Lele Chang, Lele Zang, Fei Zhu, Mingxuan Zhu, Huiqi Zhang, Yaxin Kang, Yuqin Wang, Huaiwu Lu, Yang Sun, Qin Xu","doi":"10.1186/s12916-025-04198-5","DOIUrl":"10.1186/s12916-025-04198-5","url":null,"abstract":"<p><strong>Background: </strong>Our phase 2 study has shown the efficacy and safety of sintilimab plus anlotinib as second- or later-line therapy in patients with programmed death-ligand 1 (PD-L1)-positive recurrent or metastatic cervical cancer who had failed prior chemotherapy. Here, we presented updated survival outcomes after a 3-year follow-up.</p><p><strong>Methods: </strong>Patients received a regimen comprising 200 mg of sintilimab administered once on day 1 and 10 mg of anlotinib once daily on days 1-14 every 3 weeks. Treatment was continued until disease progression or intolerable toxicity. Updated overall survival (OS) and duration of response (DoR) were reported. For patients who received subsequent treatment after progression on sintilimab plus anlotinib, the second progression-free survival (PFS2) and objective response rate on subsequent treatment (ORR2) were analyzed.</p><p><strong>Results: </strong>Between December 2019 and December 2020, a total of 42 patients were enrolled. As of July 12, 2024, the median follow-up duration was 47.2 months (range, 0.6-52.9). Median OS was 17.8 months (95% confidence interval [CI], 12.3-36.5) for 42 patients, and the median DoR was 13.2 months (95% CI, 8.2-41.8) for 23 patients with objective response. Median PFS2 was 23.6 months (95% CI, 12.5-29.8) and the ORR2 was 46.1% in 13 patients. Multivariate analysis identified PIK3CA mutation (hazard ratio = 3.43; 95% CI, 1.04-11.30; P = 0.043) as an independent prognostic factor for OS. The incidence of grade ≥ 3 treatment-related adverse events did not increase with extended follow-up.</p><p><strong>Conclusions: </strong>Long-term follow-up showed persistent antitumor activity and maintained safety of sintilimab plus anlotinib in pre-treated patients with PD-L1-positive advanced cervical cancer.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"369"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538864","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}