Pub Date : 2026-01-21DOI: 10.1016/S2352-4642(25)00339-6
Anna Turkova MD , Ellen White PhD , Avy Violari FCPaed , Prof Hilda A Mujuru MMed , Adeodata R Kekitiinwa MMed , Abbas Lugemwa MD , Elizabeth Kaudha MMed , Sathaporn Na-Rajsima MD , Grace M Ahimbisibwe MSc , Ebrahim Variavae FCP[SA] , Prof Moherndran Archary PhD , Yasmeen Akhalwaya MBChB , Thanyawee Puthanakit MD , Mutsa Bwakura-Dangarembizi PhD , Dickson Bbuye MBChB , Mariam Kasozi BSc , Afaaf Liberty MBChB , Christoph Königs PhD , Steven B Welch FRCPCH , Yoann Riault MSc , Peter Zuidewind
<div><h3>Background</h3><div>ODYSSEY trial showed superior efficacy of dolutegravir-based antiretroviral therapy (ART) versus then-current, non-dolutegravir standard of care over 96 weeks in children and adolescents living with HIV. The aim of this ancillary analysis was to compare anthropometric and body composition outcomes, including weight, height, BMI-for-age Z score, weight-for-age and height-for-age Z scores (<14 kg), mid-upper-arm circumference (MUAC), waist circumference, hip circumference, and body fat percentage, as well as metabolic outcomes (lipids and glucose), between dolutegravir and standard of care over approximately 5 years of follow-up.</div></div><div><h3>Methods</h3><div>In this open-label, randomised, non-inferiority trial, children (aged ≥4 weeks and <18 years), weighing 3 kg or more, starting first-line ART (ODYSSEY-A) or switching to second-line ART (ODYSSEY-B) were enrolled in 29 centres in Germany, Portugal, South Africa, Spain, Thailand, Uganda, Zimbabwe, and the UK in two cohorts (children weighing ≥14 kg and children weighing <14 kg). Treatment effects (dolutegravir <em>vs</em> standard of care) were estimated on randomised allocation, accounting for treatment switches (substantial in standard of care arm during extended follow-up) through censoring and inverse-probability-of-censoring-weights. Changes in continuous outcomes were compared using linear mixed models, accounting for correlated slope and baseline value. Proportions of participants with unfavourable outcomes were compared using logistic mixed models. ODYSSEY is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT02259127</span><svg><path></path></svg></span>, EUDRACT, 2014-002632-14, and ISRCTN, ISRCTN91737921.</div></div><div><h3>Findings</h3><div>Between Sept 20, 2016, and Aug 26, 2019, 792 children were randomly assigned (392 to dolutegravir and 400 to standard of care). Of 707 children in the 14 kg or more cohort, 311 received first-line ART (ODYSSEY-A; 145 [92%] of 157 received efavirenz-based ART as standard of care) and 396 received second-line ART (ODYSSEY-B; 195 [98%] of 200 received boosted protease inhibitors as standard of care). Of 85 children in the less than 14 kg cohort, 72 received first-line ART (32 [74%] of 43 received lopinavir–ritonavir as first-line or second-line standard of care). Median follow-up on randomised allocation was 287 weeks (IQR 240–311) on dolutegravir-based ART and 205 weeks (168–240) on standard of care in the 14 kg or more cohort, and 220 weeks (208–232) on dolutegravir-based ART and 144 weeks (127–192) on standard of care in the less than 14 kg cohort. In the 14 kg or more cohort, 345 (49%) were female and 362 (51%) were male, 623 (88%) were Black African, median enrolment age was 12·2 years (IQR 9·1 to 14·9), weight 30·7 kg (23·4 to 43·0), and BMI-for-age Z score –0·6 (–1·4 to 0·1); 35 (5%) were overweight and six (1%) were obese. At week 240, adjusted mea
{"title":"Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial","authors":"Anna Turkova MD , Ellen White PhD , Avy Violari FCPaed , Prof Hilda A Mujuru MMed , Adeodata R Kekitiinwa MMed , Abbas Lugemwa MD , Elizabeth Kaudha MMed , Sathaporn Na-Rajsima MD , Grace M Ahimbisibwe MSc , Ebrahim Variavae FCP[SA] , Prof Moherndran Archary PhD , Yasmeen Akhalwaya MBChB , Thanyawee Puthanakit MD , Mutsa Bwakura-Dangarembizi PhD , Dickson Bbuye MBChB , Mariam Kasozi BSc , Afaaf Liberty MBChB , Christoph Königs PhD , Steven B Welch FRCPCH , Yoann Riault MSc , Peter Zuidewind","doi":"10.1016/S2352-4642(25)00339-6","DOIUrl":"10.1016/S2352-4642(25)00339-6","url":null,"abstract":"<div><h3>Background</h3><div>ODYSSEY trial showed superior efficacy of dolutegravir-based antiretroviral therapy (ART) versus then-current, non-dolutegravir standard of care over 96 weeks in children and adolescents living with HIV. The aim of this ancillary analysis was to compare anthropometric and body composition outcomes, including weight, height, BMI-for-age Z score, weight-for-age and height-for-age Z scores (<14 kg), mid-upper-arm circumference (MUAC), waist circumference, hip circumference, and body fat percentage, as well as metabolic outcomes (lipids and glucose), between dolutegravir and standard of care over approximately 5 years of follow-up.</div></div><div><h3>Methods</h3><div>In this open-label, randomised, non-inferiority trial, children (aged ≥4 weeks and <18 years), weighing 3 kg or more, starting first-line ART (ODYSSEY-A) or switching to second-line ART (ODYSSEY-B) were enrolled in 29 centres in Germany, Portugal, South Africa, Spain, Thailand, Uganda, Zimbabwe, and the UK in two cohorts (children weighing ≥14 kg and children weighing <14 kg). Treatment effects (dolutegravir <em>vs</em> standard of care) were estimated on randomised allocation, accounting for treatment switches (substantial in standard of care arm during extended follow-up) through censoring and inverse-probability-of-censoring-weights. Changes in continuous outcomes were compared using linear mixed models, accounting for correlated slope and baseline value. Proportions of participants with unfavourable outcomes were compared using logistic mixed models. ODYSSEY is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT02259127</span><svg><path></path></svg></span>, EUDRACT, 2014-002632-14, and ISRCTN, ISRCTN91737921.</div></div><div><h3>Findings</h3><div>Between Sept 20, 2016, and Aug 26, 2019, 792 children were randomly assigned (392 to dolutegravir and 400 to standard of care). Of 707 children in the 14 kg or more cohort, 311 received first-line ART (ODYSSEY-A; 145 [92%] of 157 received efavirenz-based ART as standard of care) and 396 received second-line ART (ODYSSEY-B; 195 [98%] of 200 received boosted protease inhibitors as standard of care). Of 85 children in the less than 14 kg cohort, 72 received first-line ART (32 [74%] of 43 received lopinavir–ritonavir as first-line or second-line standard of care). Median follow-up on randomised allocation was 287 weeks (IQR 240–311) on dolutegravir-based ART and 205 weeks (168–240) on standard of care in the 14 kg or more cohort, and 220 weeks (208–232) on dolutegravir-based ART and 144 weeks (127–192) on standard of care in the less than 14 kg cohort. In the 14 kg or more cohort, 345 (49%) were female and 362 (51%) were male, 623 (88%) were Black African, median enrolment age was 12·2 years (IQR 9·1 to 14·9), weight 30·7 kg (23·4 to 43·0), and BMI-for-age Z score –0·6 (–1·4 to 0·1); 35 (5%) were overweight and six (1%) were obese. At week 240, adjusted mea","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 3","pages":"Pages 189-202"},"PeriodicalIF":15.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/S2352-4642(26)00007-6
Zahed Katurji, Asha Ali, Mohamad Khalife, Robin Basu Roy
{"title":"Nobody can be immune to the deaths of this girl, her family, and the paramedics who tried to save her","authors":"Zahed Katurji, Asha Ali, Mohamad Khalife, Robin Basu Roy","doi":"10.1016/S2352-4642(26)00007-6","DOIUrl":"10.1016/S2352-4642(26)00007-6","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 3","pages":"Page 155"},"PeriodicalIF":15.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S2352-4642(25)00386-4
Clare Craig
{"title":"Vascular and inflammatory diseases after COVID-19 infection and vaccination in children","authors":"Clare Craig","doi":"10.1016/S2352-4642(25)00386-4","DOIUrl":"10.1016/S2352-4642(25)00386-4","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Pages e5-e6"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S2352-4642(25)00382-7
Angela M Wood , Alexia Sampri , Thomas Bolton
{"title":"Vascular and inflammatory diseases after COVID-19 infection and vaccination in children – Authors' reply","authors":"Angela M Wood , Alexia Sampri , Thomas Bolton","doi":"10.1016/S2352-4642(25)00382-7","DOIUrl":"10.1016/S2352-4642(25)00382-7","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Pages e6-e8"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S2352-4642(25)00383-9
Jules Morgan
{"title":"Chandy John: Using his heart and head for change that matters","authors":"Jules Morgan","doi":"10.1016/S2352-4642(25)00383-9","DOIUrl":"10.1016/S2352-4642(25)00383-9","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Page 80"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S2352-4642(25)00377-3
Alberto Donzelli
{"title":"Vascular and inflammatory diseases after COVID-19 infection and vaccination in children","authors":"Alberto Donzelli","doi":"10.1016/S2352-4642(25)00377-3","DOIUrl":"10.1016/S2352-4642(25)00377-3","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Page e4"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Delayed puberty has been associated with adverse metabolic outcomes, yet longitudinal evidence on its relation to type 2 diabetes risk is scarce. We aimed to investigate the association between delayed puberty during adolescence and early-adult-onset type 2 diabetes in male adolescents.
Methods
This nationwide, population-based, retrospective cohort study included Israeli male adolescents aged 16–19 years who were examined before military recruitment during 1992–2015 and followed up until Dec 31, 2019. Exclusion criteria were diabetes at the baseline medical assessment, hypogonadotropic hypogonadism, missing height or weight data, and death before the establishment of the Israeli National Diabetes Registry (INDR) in 2012. Delayed puberty was diagnosed by board-certified paediatric endocrinologists, based on physical examinations and laboratory evaluations. By linking data to the INDR, diabetes was identified by: glycated haemoglobin concentrations of more than 6·5%, serum glucose concentrations of more than 200 mg/dL in two tests at least 1 month apart, or repeated purchases of glucose-lowering medications. Type 2 diabetes was classified according to medication records, which underwent quality assessment to ensure accuracy. Cox proportional hazards models were applied.
Findings
The study included 964 108 Israeli male adolescents (mean age at evaluation 17·3 years [SD 0·5]). Delayed puberty was diagnosed in 4307 males, whereas 959 801 did not have delayed puberty. During a cumulative follow-up of 15 242 068 person-years, type 2 diabetes was diagnosed in 111 (2·6%) individuals with delayed puberty (mean age at diagnosis 35·5 years [SD 5·2]) and 6259 (0·7%) individuals without delayed puberty (36·8 years [4·7]). The respective incidence rates of type 2 diabetes were 140·3 cases per 105 person-years (95% CI 114·2–166·4) and 41·3 cases per 105 person-years (40·3–42·3; p<0·0001); absolute difference 99·0 (72·9–125·1). After adjustment for age, year of study entry, education, cognitive performance, residential socioeconomic status, and country of birth, delayed puberty was associated with an increased risk of type 2 diabetes (hazard ratio [HR] 2·47 [95% CI 2·04–2·99], p<0·0001). Additional adjustment for baseline BMI attenuated but did not eliminate the association (HR 1·37 [1·13–1·66]; p=0·0015). The findings persisted across extensive sensitivity analyses.
Interpretation
Male adolescents with delayed puberty are at increased risk of developing type 2 diabetes in early adulthood, independent of BMI. Our findings suggest that delayed puberty is not a benign developmental variant, but might serve as an early marker of increased risk for later abnormal glucose metabolism.
{"title":"Delayed puberty and early-onset type 2 diabetes risk: a nationwide cohort study of male adolescents in Israel","authors":"Prof Orit Pinhas-Hamiel MD , Maya Simchoni MD , Estela Derazne MSc , Cole D Bendor MD , Avishai M Tsur MD , Adi Vinograd MD , Miri Lutski PhD , Inbar Zucker MD , Prof Vibha Singhal MD , Prof Hertzel C Gerstein MD , Prof Arnon Afek MD , Prof Amir Tirosh MD , Prof Gilad Twig MD","doi":"10.1016/S2352-4642(25)00333-5","DOIUrl":"10.1016/S2352-4642(25)00333-5","url":null,"abstract":"<div><h3>Background</h3><div>Delayed puberty has been associated with adverse metabolic outcomes, yet longitudinal evidence on its relation to type 2 diabetes risk is scarce. We aimed to investigate the association between delayed puberty during adolescence and early-adult-onset type 2 diabetes in male adolescents.</div></div><div><h3>Methods</h3><div>This nationwide, population-based, retrospective cohort study included Israeli male adolescents aged 16–19 years who were examined before military recruitment during 1992–2015 and followed up until Dec 31, 2019. Exclusion criteria were diabetes at the baseline medical assessment, hypogonadotropic hypogonadism, missing height or weight data, and death before the establishment of the Israeli National Diabetes Registry (INDR) in 2012. Delayed puberty was diagnosed by board-certified paediatric endocrinologists, based on physical examinations and laboratory evaluations. By linking data to the INDR, diabetes was identified by: glycated haemoglobin concentrations of more than 6·5%, serum glucose concentrations of more than 200 mg/dL in two tests at least 1 month apart, or repeated purchases of glucose-lowering medications. Type 2 diabetes was classified according to medication records, which underwent quality assessment to ensure accuracy. Cox proportional hazards models were applied.</div></div><div><h3>Findings</h3><div>The study included 964 108 Israeli male adolescents (mean age at evaluation 17·3 years [SD 0·5]). Delayed puberty was diagnosed in 4307 males, whereas 959 801 did not have delayed puberty. During a cumulative follow-up of 15 242 068 person-years, type 2 diabetes was diagnosed in 111 (2·6%) individuals with delayed puberty (mean age at diagnosis 35·5 years [SD 5·2]) and 6259 (0·7%) individuals without delayed puberty (36·8 years [4·7]). The respective incidence rates of type 2 diabetes were 140·3 cases per 10<sup>5</sup> person-years (95% CI 114·2–166·4) and 41·3 cases per 10<sup>5</sup> person-years (40·3–42·3; p<0·0001); absolute difference 99·0 (72·9–125·1). After adjustment for age, year of study entry, education, cognitive performance, residential socioeconomic status, and country of birth, delayed puberty was associated with an increased risk of type 2 diabetes (hazard ratio [HR] 2·47 [95% CI 2·04–2·99], p<0·0001). Additional adjustment for baseline BMI attenuated but did not eliminate the association (HR 1·37 [1·13–1·66]; p=0·0015). The findings persisted across extensive sensitivity analyses.</div></div><div><h3>Interpretation</h3><div>Male adolescents with delayed puberty are at increased risk of developing type 2 diabetes in early adulthood, independent of BMI. Our findings suggest that delayed puberty is not a benign developmental variant, but might serve as an early marker of increased risk for later abnormal glucose metabolism.</div></div><div><h3>Funding</h3><div>Sheba Medical Center.</div></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Pages 103-110"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S2352-4642(25)00384-0
The Lancet Child & Adolescent Health
{"title":"Keeping children and young people safe in all their spaces","authors":"The Lancet Child & Adolescent Health","doi":"10.1016/S2352-4642(25)00384-0","DOIUrl":"10.1016/S2352-4642(25)00384-0","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"10 2","pages":"Page 71"},"PeriodicalIF":15.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：