Pub Date : 2024-09-05DOI: 10.1038/s41591-024-03236-8
Simar S. Bajaj, Ahmed M. Ahmed, Valerie E. Stone
{"title":"Medicine’s DEI backlash offers an opportunity to refocus on evidence-based approaches","authors":"Simar S. Bajaj, Ahmed M. Ahmed, Valerie E. Stone","doi":"10.1038/s41591-024-03236-8","DOIUrl":"10.1038/s41591-024-03236-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3040-3041"},"PeriodicalIF":58.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140603","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 : 2024-09-03DOI: 10.1038/s41591-024-03245-7
Claudia Hanson, Jeroen de Bont, Kristi Sidney Annerstedt, Maria del Rosario Alsina, Federica Nobile, Nathalie Roos, Peter Waiswa, Andrea Pembe, Jean-Paul Dossou, Effie Chipeta, Lenka Benova, Hussein Kidanto, Cherie Part, Massimo Stafoggia, Veronique Filippi, Petter Ljungman
Growing evidence suggests that extreme heat events affect both pregnant women and their infants, but few studies are available from sub-Saharan Africa. Using data from 138,015 singleton births in 16 hospitals in Benin, Malawi, Tanzania and Uganda, we investigated the association between extreme heat and early perinatal deaths, including antepartum and intrapartum stillbirths, and deaths within 24 h after birth using a time-stratified case–crossover design. We observed an association between an increase from the 75th to the 99th percentile in mean temperature 1 week (lag 0–6 d) before childbirth and perinatal mortality (odds ratio (OR) = 1.34 (95% confidence interval (CI) 1.01–1.78)). The estimates for stillbirths were similarly positive, but CIs included unity: OR = 1.29 (95% CI 0.95–1.77) for all stillbirths, OR = 1.18 (95% CI 0.71–1.95) for antepartum stillbirths and OR = 1.64 (95% CI 0.74–3.63) for intrapartum stillbirths. The cumulative exposure–response curve suggested that the steepest slopes for heat for intrapartum stillbirths and associations were stronger during the hottest seasons. We conclude that short-term heat exposure may increase mortality risks, particularly for intrapartum stillbirths, raising the importance of improved intrapartum care. Data collected from 138,015 hospital-based singleton births in four sub-Saharan African countries revealed an association between heat exposure in the week leading up to the birth and perinatal mortality.
越来越多的证据表明，极端高温事件对孕妇和婴儿都有影响，但撒哈拉以南非洲地区的研究却很少。我们利用贝宁、马拉维、坦桑尼亚和乌干达 16 家医院 138,015 例单胎新生儿的数据，采用时间分层病例交叉设计，研究了极端高温与围产期早期死亡（包括产前和产中死胎）以及产后 24 小时内死亡之间的关系。我们观察到，分娩前 1 周（滞后 0-6 d）平均气温从第 75 百分位数升高至第 99 百分位数与围产期死亡率之间存在关联（几率比 (OR) = 1.34（95% 置信区间 (CI) 1.01-1.78））。死胎的估计值同样为正，但 CI 包括统一值：所有死胎的 OR = 1.29（95% CI 0.95-1.77），产前死胎的 OR = 1.18（95% CI 0.71-1.95），产中死胎的 OR = 1.64（95% CI 0.74-3.63）。累积暴露-反应曲线表明，在最炎热的季节，产前死胎的热斜率最陡，相关性也更强。我们的结论是，短期暴露于高温可能会增加死亡风险，尤其是产中死胎，因此改善产中护理非常重要。
{"title":"A time-stratified, case–crossover study of heat exposure and perinatal mortality from 16 hospitals in sub-Saharan Africa","authors":"Claudia Hanson, Jeroen de Bont, Kristi Sidney Annerstedt, Maria del Rosario Alsina, Federica Nobile, Nathalie Roos, Peter Waiswa, Andrea Pembe, Jean-Paul Dossou, Effie Chipeta, Lenka Benova, Hussein Kidanto, Cherie Part, Massimo Stafoggia, Veronique Filippi, Petter Ljungman","doi":"10.1038/s41591-024-03245-7","DOIUrl":"10.1038/s41591-024-03245-7","url":null,"abstract":"Growing evidence suggests that extreme heat events affect both pregnant women and their infants, but few studies are available from sub-Saharan Africa. Using data from 138,015 singleton births in 16 hospitals in Benin, Malawi, Tanzania and Uganda, we investigated the association between extreme heat and early perinatal deaths, including antepartum and intrapartum stillbirths, and deaths within 24 h after birth using a time-stratified case–crossover design. We observed an association between an increase from the 75th to the 99th percentile in mean temperature 1 week (lag 0–6 d) before childbirth and perinatal mortality (odds ratio (OR) = 1.34 (95% confidence interval (CI) 1.01–1.78)). The estimates for stillbirths were similarly positive, but CIs included unity: OR = 1.29 (95% CI 0.95–1.77) for all stillbirths, OR = 1.18 (95% CI 0.71–1.95) for antepartum stillbirths and OR = 1.64 (95% CI 0.74–3.63) for intrapartum stillbirths. The cumulative exposure–response curve suggested that the steepest slopes for heat for intrapartum stillbirths and associations were stronger during the hottest seasons. We conclude that short-term heat exposure may increase mortality risks, particularly for intrapartum stillbirths, raising the importance of improved intrapartum care. Data collected from 138,015 hospital-based singleton births in four sub-Saharan African countries revealed an association between heat exposure in the week leading up to the birth and perinatal mortality.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3106-3113"},"PeriodicalIF":58.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03245-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123725","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}
Pub Date : 2024-08-30DOI: 10.1038/s41591-024-03202-4
Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S. Bhatt, Daniel Modin, Safia Chatur, Brian L. Claggett, Kira Hyldekær Janstrup, Carsten Schade Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Lars Køber, Scott D. Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Tyra Grove Krause, Tor Biering-Sørensen
Digital letter interventions have proven effective in increasing influenza vaccination rates. In this trial, we sought to further refine these strategies and investigated whether the effectiveness of the strategies could be sustained across consecutive influenza seasons. We enrolled all eligible Danish citizens 65 years of age or older in a nationwide registry-based randomized implementation trial during the 2023–2024 influenza season. Households of participants were randomly assigned in a 2.45:1:1:1:1:1:1 ratio to usual care or six different behaviorally informed electronic letter-based nudges delivered before the influenza vaccination period. The primary endpoint was receipt of influenza vaccination. Statistical analyses accounted for household-level clustering. A total of 881,373 participants (mean age 74.1 ± 6.5 years, 52.1% female) were randomized across 649,487 households. The primary endpoint was met; influenza vaccination rates were higher in the pooled intervention letter group compared to usual care (76.32% versus 76.02%; difference, 0.31 percentage points; 99.29% confidence interval, 0.00–0.61; P = 0.007). Although no individual letter significantly increased influenza vaccination rates, the directionality of effect was consistent across all letters. Effectiveness was particularly pronounced in participants who had not received influenza vaccination during the preceding season (Pinteraction = 0.010). Effectiveness was consistent regardless of whether participants had received a similar electronic letter-based nudge in the preceding season (Pinteraction = 0.26). In summary, electronic letter-based nudges successfully increased influenza vaccination among older adults, and our results suggest that these highly scalable strategies can be implemented effectively and safely across consecutive vaccination seasons. ClinicalTrials.gov registration: NCT06030726 . In the second season of a series of pragmatic trials involving all Danish citizens 65 years of age or older, electronic nudges increased influenza vaccination rates significantly with respect to usual care, with higher effect in individuals not vaccinated in the previous season.
{"title":"Electronic nudges for sustained influenza vaccination uptake in older adults: the nationwide randomized NUDGE-FLU-2 trial","authors":"Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S. Bhatt, Daniel Modin, Safia Chatur, Brian L. Claggett, Kira Hyldekær Janstrup, Carsten Schade Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Lars Køber, Scott D. Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Tyra Grove Krause, Tor Biering-Sørensen","doi":"10.1038/s41591-024-03202-4","DOIUrl":"10.1038/s41591-024-03202-4","url":null,"abstract":"Digital letter interventions have proven effective in increasing influenza vaccination rates. In this trial, we sought to further refine these strategies and investigated whether the effectiveness of the strategies could be sustained across consecutive influenza seasons. We enrolled all eligible Danish citizens 65 years of age or older in a nationwide registry-based randomized implementation trial during the 2023–2024 influenza season. Households of participants were randomly assigned in a 2.45:1:1:1:1:1:1 ratio to usual care or six different behaviorally informed electronic letter-based nudges delivered before the influenza vaccination period. The primary endpoint was receipt of influenza vaccination. Statistical analyses accounted for household-level clustering. A total of 881,373 participants (mean age 74.1 ± 6.5 years, 52.1% female) were randomized across 649,487 households. The primary endpoint was met; influenza vaccination rates were higher in the pooled intervention letter group compared to usual care (76.32% versus 76.02%; difference, 0.31 percentage points; 99.29% confidence interval, 0.00–0.61; P = 0.007). Although no individual letter significantly increased influenza vaccination rates, the directionality of effect was consistent across all letters. Effectiveness was particularly pronounced in participants who had not received influenza vaccination during the preceding season (Pinteraction = 0.010). Effectiveness was consistent regardless of whether participants had received a similar electronic letter-based nudge in the preceding season (Pinteraction = 0.26). In summary, electronic letter-based nudges successfully increased influenza vaccination among older adults, and our results suggest that these highly scalable strategies can be implemented effectively and safely across consecutive vaccination seasons. ClinicalTrials.gov registration: NCT06030726 . In the second season of a series of pragmatic trials involving all Danish citizens 65 years of age or older, electronic nudges increased influenza vaccination rates significantly with respect to usual care, with higher effect in individuals not vaccinated in the previous season.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3142-3149"},"PeriodicalIF":58.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100768","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 : 2024-08-28DOI: 10.1038/s41591-024-03268-0
Bram De Laere, Alessio Crippa, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D’hondt, Rebecka Bergström, Venkatesh Chellappa, Markus Mayrhofer, Mahsan Banijamali, Anastasijia Kotsalaynen, Céline Schelstraete, Jan Pieter Vanwelkenhuyzen, Marie Hjälm-Eriksson, Linn Pettersson, Anders Ullén, Nicolaas Lumen, Gunilla Enblad, Camilla Thellenberg Karlsson, Elin Jänes, Johan Sandzén, Peter Schatteman, Maria Nyre Vigmostad, Martha Olsson, Christophe Ghysel, Brieuc Sautois, Wendy De Roock, Siska Van Bruwaene, Mats Anden, Ingrida Verbiene, Daan De Maeseneer, Els Everaert, Jochen Darras, Bjørg Y. Aksnessether, Daisy Luyten, Michiel Strijbos, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Martin Eklund, Henrik Grönberg, Johan Lindberg
{"title":"Author Correction: Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial","authors":"Bram De Laere, Alessio Crippa, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D’hondt, Rebecka Bergström, Venkatesh Chellappa, Markus Mayrhofer, Mahsan Banijamali, Anastasijia Kotsalaynen, Céline Schelstraete, Jan Pieter Vanwelkenhuyzen, Marie Hjälm-Eriksson, Linn Pettersson, Anders Ullén, Nicolaas Lumen, Gunilla Enblad, Camilla Thellenberg Karlsson, Elin Jänes, Johan Sandzén, Peter Schatteman, Maria Nyre Vigmostad, Martha Olsson, Christophe Ghysel, Brieuc Sautois, Wendy De Roock, Siska Van Bruwaene, Mats Anden, Ingrida Verbiene, Daan De Maeseneer, Els Everaert, Jochen Darras, Bjørg Y. Aksnessether, Daisy Luyten, Michiel Strijbos, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Martin Eklund, Henrik Grönberg, Johan Lindberg","doi":"10.1038/s41591-024-03268-0","DOIUrl":"10.1038/s41591-024-03268-0","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3381-3381"},"PeriodicalIF":58.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03268-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093564","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}
Pub Date : 2024-08-23DOI: 10.1038/s41591-024-03206-0
Omid Azimaraghi, Maíra I. Rudolph, Karuna Wongtangman, Felix Borngaesser, Maya Doehne, Pauline Y. Ng, Dario von Wedel, Annika Eyth, Fengwei Zou, Christopher Tam, William J. Sauer, Michael E. Kiyatkin, Timothy T. Houle, Ibraheem M. Karaye, Ling Zhang, Maximilian S. Schaefer, Simon T. Schaefer, Carina P. Himes, Aline M. Grimm, Olubukola O. Nafiu, Christian Mpody, Aiman Suleiman, Brendon M. Stiles, Luigi Di Biase, Mario J. Garcia, The Boston-NYC Afib after non-cardiac surgery collaborators Consortium, Deepak L. Bhatt, Matthias Eikermann
The role of antithrombotic therapy in the prevention of ischemic stroke after non-cardiac surgery is unclear. In this study, we tested the hypothesis that the association of new-onset postoperative atrial fibrillation (POAF) on ischemic stroke can be mitigated by postoperative oral anticoagulation therapy. Of 251,837 adult patients (155,111 female (61.6%) and 96,726 male (38.4%)) who underwent non-cardiac surgical procedures at two sites, POAF was detected in 4,538 (1.8%) patients. The occurrence of POAF was associated with increased 1-year ischemic stroke risk (3.6% versus 2.3%; adjusted risk ratio (RRadj) = 1.60 (95% confidence interval (CI): 1.37–1.87), P < 0.001). In patients with POAF, the risk of developing stroke attributable to POAF was 1.81 (95% CI: 1.44–2.28; P < 0.001) without oral anticoagulation, whereas, in patients treated with anticoagulation, no significant association was observed between POAF and stroke (RRadj = 1.04 (95% CI: 0.71–1.51), P = 0.847, P for interaction = 0.013). Furthermore, we derived and validated a computational model for the prediction of POAF after non-cardiac surgery based on demographics, comorbidities and procedural risk. These findings suggest that POAF is predictable and associated with an increased risk of postoperative ischemic stroke in patients who do not receive postoperative anticoagulation. In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.
{"title":"Role of anticoagulation therapy in modifying stroke risk associated with new-onset atrial fibrillation after non-cardiac surgery","authors":"Omid Azimaraghi, Maíra I. Rudolph, Karuna Wongtangman, Felix Borngaesser, Maya Doehne, Pauline Y. Ng, Dario von Wedel, Annika Eyth, Fengwei Zou, Christopher Tam, William J. Sauer, Michael E. Kiyatkin, Timothy T. Houle, Ibraheem M. Karaye, Ling Zhang, Maximilian S. Schaefer, Simon T. Schaefer, Carina P. Himes, Aline M. Grimm, Olubukola O. Nafiu, Christian Mpody, Aiman Suleiman, Brendon M. Stiles, Luigi Di Biase, Mario J. Garcia, The Boston-NYC Afib after non-cardiac surgery collaborators Consortium, Deepak L. Bhatt, Matthias Eikermann","doi":"10.1038/s41591-024-03206-0","DOIUrl":"10.1038/s41591-024-03206-0","url":null,"abstract":"The role of antithrombotic therapy in the prevention of ischemic stroke after non-cardiac surgery is unclear. In this study, we tested the hypothesis that the association of new-onset postoperative atrial fibrillation (POAF) on ischemic stroke can be mitigated by postoperative oral anticoagulation therapy. Of 251,837 adult patients (155,111 female (61.6%) and 96,726 male (38.4%)) who underwent non-cardiac surgical procedures at two sites, POAF was detected in 4,538 (1.8%) patients. The occurrence of POAF was associated with increased 1-year ischemic stroke risk (3.6% versus 2.3%; adjusted risk ratio (RRadj) = 1.60 (95% confidence interval (CI): 1.37–1.87), P < 0.001). In patients with POAF, the risk of developing stroke attributable to POAF was 1.81 (95% CI: 1.44–2.28; P < 0.001) without oral anticoagulation, whereas, in patients treated with anticoagulation, no significant association was observed between POAF and stroke (RRadj = 1.04 (95% CI: 0.71–1.51), P = 0.847, P for interaction = 0.013). Furthermore, we derived and validated a computational model for the prediction of POAF after non-cardiac surgery based on demographics, comorbidities and procedural risk. These findings suggest that POAF is predictable and associated with an increased risk of postoperative ischemic stroke in patients who do not receive postoperative anticoagulation. In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3310-3317"},"PeriodicalIF":58.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042607","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 : 2024-08-23DOI: 10.1038/s41591-024-03205-1
Rebecca Hémono, Emmyson Gatare, Laetitia Kayitesi, Lauren A. Hunter, Laura Packel, Nicole Ippoliti, Diego Cerecero-García, David Contreras-Loya, Paola Gadsden, Sergio Bautista-Arredondo, Felix Sayinzoga, Michael Mugisha, Stefano M. Bertozzi, Rebecca Hope, Sandra I. McCoy
We conducted a cluster-randomized hybrid effectiveness-implementation study of CyberRwanda, a digital family planning and reproductive health intervention for Rwandan adolescents. Sixty schools were randomized 1:1:1 to control or to one of two implementation models—self-service (self-guided access on tablets) or facilitated (peer-led clubs plus tablet access) with no masking. Eligible participants were aged 12–19 years, in secondary school levels 1 or 2, and willing to provide consent or assent/parental consent and contact information for follow-up. In 2021, 6,078 randomly selected adolescents were enrolled. At 24 months, 91.3% of participants were retained and included in the primary intention-to-treat analyses (control, n = 1,845; self-service, n = 1,849 and facilitated, n = 1,858). There were no adverse events related to the study. CyberRwanda did not affect the primary outcomes of modern contraceptive use (prevalence ratio (PR) = 1.04; 95% confidence interval (CI) = 0.76, 1.42), childbearing (PR = 1.33; 95% CI = 0.71, 2.50) and HIV testing (PR = 1.00; 95% CI = 0.91, 1.11) in the full sample. Significantly higher modern contraceptive use observed in the CyberRwanda facilitated arm in a prespecified analysis of sexually active participants suggests that longer-term evaluation is needed to examine effects as more of the study population becomes sexually active and has increased demand for contraception. ClinicalTrials.gov registration: NCT04198272 . An implementation trial conducted across 60 schools in Rwanda found that CyberRwanda, a digital, school-based intervention, did not affect the primary outcomes of modern contraceptive use, childbearing and HIV testing among adolescents but was associated with higher contraceptive use among sexually active participants.
{"title":"Effect of a digital school-based intervention on adolescent family planning and reproductive health in Rwanda: a cluster-randomized trial","authors":"Rebecca Hémono, Emmyson Gatare, Laetitia Kayitesi, Lauren A. Hunter, Laura Packel, Nicole Ippoliti, Diego Cerecero-García, David Contreras-Loya, Paola Gadsden, Sergio Bautista-Arredondo, Felix Sayinzoga, Michael Mugisha, Stefano M. Bertozzi, Rebecca Hope, Sandra I. McCoy","doi":"10.1038/s41591-024-03205-1","DOIUrl":"10.1038/s41591-024-03205-1","url":null,"abstract":"We conducted a cluster-randomized hybrid effectiveness-implementation study of CyberRwanda, a digital family planning and reproductive health intervention for Rwandan adolescents. Sixty schools were randomized 1:1:1 to control or to one of two implementation models—self-service (self-guided access on tablets) or facilitated (peer-led clubs plus tablet access) with no masking. Eligible participants were aged 12–19 years, in secondary school levels 1 or 2, and willing to provide consent or assent/parental consent and contact information for follow-up. In 2021, 6,078 randomly selected adolescents were enrolled. At 24 months, 91.3% of participants were retained and included in the primary intention-to-treat analyses (control, n = 1,845; self-service, n = 1,849 and facilitated, n = 1,858). There were no adverse events related to the study. CyberRwanda did not affect the primary outcomes of modern contraceptive use (prevalence ratio (PR) = 1.04; 95% confidence interval (CI) = 0.76, 1.42), childbearing (PR = 1.33; 95% CI = 0.71, 2.50) and HIV testing (PR = 1.00; 95% CI = 0.91, 1.11) in the full sample. Significantly higher modern contraceptive use observed in the CyberRwanda facilitated arm in a prespecified analysis of sexually active participants suggests that longer-term evaluation is needed to examine effects as more of the study population becomes sexually active and has increased demand for contraception. ClinicalTrials.gov registration: NCT04198272 . An implementation trial conducted across 60 schools in Rwanda found that CyberRwanda, a digital, school-based intervention, did not affect the primary outcomes of modern contraceptive use, childbearing and HIV testing among adolescents but was associated with higher contraceptive use among sexually active participants.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3121-3128"},"PeriodicalIF":58.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042637","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 : 2024-08-21DOI: 10.1038/s41591-024-03167-4
Justin Z. Wang, Vikas Patil, Alexander P. Landry, Chloe Gui, Andrew Ajisebutu, Jeff Liu, Olli Saarela, Stephanie L. Pugh, Minhee Won, Zeel Patel, Rebeca Yakubov, Ramneet Kaloti, Christopher Wilson, Aaron Cohen-Gadol, Mohamed A. Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Damian A. Almiron Bonnin, Eric C. Holland, Tim J. Kruser, Jill S. Barnholtz-Sloan, Andrew E. Sloan, Craig Horbinski, Silky Chotai, Lola B. Chambless, Andrew Gao, Alexander D. Rebchuk, Serge Makarenko, Stephen Yip, Felix Sahm, Sybren L. N. Maas, Derek S. Tsang, The International Consortium on Meningiomas (ICOM), C. Leland Rogers, Kenneth Aldape, Farshad Nassiri, Gelareh Zadeh
Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making. In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.
{"title":"Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma","authors":"Justin Z. Wang, Vikas Patil, Alexander P. Landry, Chloe Gui, Andrew Ajisebutu, Jeff Liu, Olli Saarela, Stephanie L. Pugh, Minhee Won, Zeel Patel, Rebeca Yakubov, Ramneet Kaloti, Christopher Wilson, Aaron Cohen-Gadol, Mohamed A. Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Damian A. Almiron Bonnin, Eric C. Holland, Tim J. Kruser, Jill S. Barnholtz-Sloan, Andrew E. Sloan, Craig Horbinski, Silky Chotai, Lola B. Chambless, Andrew Gao, Alexander D. Rebchuk, Serge Makarenko, Stephen Yip, Felix Sahm, Sybren L. N. Maas, Derek S. Tsang, The International Consortium on Meningiomas (ICOM), C. Leland Rogers, Kenneth Aldape, Farshad Nassiri, Gelareh Zadeh","doi":"10.1038/s41591-024-03167-4","DOIUrl":"10.1038/s41591-024-03167-4","url":null,"abstract":"Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making. In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3173-3183"},"PeriodicalIF":58.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03167-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013820","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}
Pub Date : 2024-08-21DOI: 10.1038/d41591-024-00063-9
Nicaise Ndembi
Africa CDC has declared its first Public Health Emergency of Continental Security. Africa CDC has declared its first Public Health Emergency of Continental Security.
{"title":"Mpox is a public health emergency — what happens now?","authors":"Nicaise Ndembi","doi":"10.1038/d41591-024-00063-9","DOIUrl":"10.1038/d41591-024-00063-9","url":null,"abstract":"Africa CDC has declared its first Public Health Emergency of Continental Security. Africa CDC has declared its first Public Health Emergency of Continental Security.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3044-3044"},"PeriodicalIF":58.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/d41591-024-00063-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018097","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}
Pub Date : 2024-08-20DOI: 10.1038/s41591-024-03204-2
Bram De Laere, Alessio Crippa, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D’hondt, Rebecka Bergström, Venkatesh Chellappa, Markus Mayrhofer, Mahsan Banijamali, Anastasijia Kotsalaynen, Céline Schelstraete, Jan Pieter Vanwelkenhuyzen, Marie Hjälm-Eriksson, Linn Pettersson, Anders Ullén, Nicolaas Lumen, Gunilla Enblad, Camilla Thellenberg Karlsson, Elin Jänes, Johan Sandzén, Peter Schatteman, Maria Nyre Vigmostad, Martha Olsson, Christophe Ghysel, Brieuc Sautois, Wendy De Roock, Siska Van Bruwaene, Mats Anden, Ingrida Verbiene, Daan De Maeseneer, Els Everaert, Jochen Darras, Bjørg Y. Aksnessether, Daisy Luyten, Michiel Strijbos, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Martin Eklund, Henrik Grönberg, Johan Lindberg
ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician’s choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician’s choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or ‘all’ patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician’s choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2–ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician’s choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 . In a biomarker-driven, outcome-adaptive platform trial for patients with metastatic castration-resistant prostate cancer, androgen receptor pathway inhibitors showed longer survival with respect to taxanes and physician’s choice treatment.
{"title":"Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial","authors":"Bram De Laere, Alessio Crippa, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D’hondt, Rebecka Bergström, Venkatesh Chellappa, Markus Mayrhofer, Mahsan Banijamali, Anastasijia Kotsalaynen, Céline Schelstraete, Jan Pieter Vanwelkenhuyzen, Marie Hjälm-Eriksson, Linn Pettersson, Anders Ullén, Nicolaas Lumen, Gunilla Enblad, Camilla Thellenberg Karlsson, Elin Jänes, Johan Sandzén, Peter Schatteman, Maria Nyre Vigmostad, Martha Olsson, Christophe Ghysel, Brieuc Sautois, Wendy De Roock, Siska Van Bruwaene, Mats Anden, Ingrida Verbiene, Daan De Maeseneer, Els Everaert, Jochen Darras, Bjørg Y. Aksnessether, Daisy Luyten, Michiel Strijbos, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Martin Eklund, Henrik Grönberg, Johan Lindberg","doi":"10.1038/s41591-024-03204-2","DOIUrl":"10.1038/s41591-024-03204-2","url":null,"abstract":"ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician’s choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician’s choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or ‘all’ patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician’s choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2–ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician’s choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 . In a biomarker-driven, outcome-adaptive platform trial for patients with metastatic castration-resistant prostate cancer, androgen receptor pathway inhibitors showed longer survival with respect to taxanes and physician’s choice treatment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3291-3302"},"PeriodicalIF":58.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03204-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007587","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}
Pub Date : 2024-08-19DOI: 10.1038/s41591-024-03196-z
Carina R. Oehrn, Stephanie Cernera, Lauren H. Hammer, Maria Shcherbakova, Jiaang Yao, Amelia Hahn, Sarah Wang, Jill L. Ostrem, Simon Little, Philip A. Starr
Deep brain stimulation (DBS) is a widely used therapy for Parkinson’s disease (PD) but lacks dynamic responsiveness to changing clinical and neural states. Feedback control might improve therapeutic effectiveness, but the optimal control strategy and additional benefits of ‘adaptive’ neurostimulation are unclear. Here we present the results of a blinded randomized cross-over pilot trial aimed at determining the neural correlates of specific motor signs in individuals with PD and the feasibility of using these signals to drive adaptive DBS. Four male patients with PD were recruited from a population undergoing DBS implantation for motor fluctuations, with each patient receiving adaptive DBS and continuous DBS. We identified stimulation-entrained gamma oscillations in the subthalamic nucleus or motor cortex as optimal markers of high versus low dopaminergic states and their associated residual motor signs in all four patients. We then demonstrated improved motor symptoms and quality of life with adaptive compared to clinically optimized standard stimulation. The results of this pilot trial highlight the promise of personalized adaptive neurostimulation in PD based on data-driven selection of neural signals. Furthermore, these findings provide the foundation for further larger clinical trials to evaluate the efficacy of personalized adaptive neurostimulation in PD and other neurological disorders. ClinicalTrials.gov registration: NCT03582891 . A small clinical study shows that adaptive deep brain stimulation (DBS), based on real-time brain activity, for Parkinson’s disease significantly improved motor symptoms and quality of life compared with conventional DBS.
{"title":"Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson’s disease: a blinded randomized feasibility trial","authors":"Carina R. Oehrn, Stephanie Cernera, Lauren H. Hammer, Maria Shcherbakova, Jiaang Yao, Amelia Hahn, Sarah Wang, Jill L. Ostrem, Simon Little, Philip A. Starr","doi":"10.1038/s41591-024-03196-z","DOIUrl":"10.1038/s41591-024-03196-z","url":null,"abstract":"Deep brain stimulation (DBS) is a widely used therapy for Parkinson’s disease (PD) but lacks dynamic responsiveness to changing clinical and neural states. Feedback control might improve therapeutic effectiveness, but the optimal control strategy and additional benefits of ‘adaptive’ neurostimulation are unclear. Here we present the results of a blinded randomized cross-over pilot trial aimed at determining the neural correlates of specific motor signs in individuals with PD and the feasibility of using these signals to drive adaptive DBS. Four male patients with PD were recruited from a population undergoing DBS implantation for motor fluctuations, with each patient receiving adaptive DBS and continuous DBS. We identified stimulation-entrained gamma oscillations in the subthalamic nucleus or motor cortex as optimal markers of high versus low dopaminergic states and their associated residual motor signs in all four patients. We then demonstrated improved motor symptoms and quality of life with adaptive compared to clinically optimized standard stimulation. The results of this pilot trial highlight the promise of personalized adaptive neurostimulation in PD based on data-driven selection of neural signals. Furthermore, these findings provide the foundation for further larger clinical trials to evaluate the efficacy of personalized adaptive neurostimulation in PD and other neurological disorders. ClinicalTrials.gov registration: NCT03582891 . A small clinical study shows that adaptive deep brain stimulation (DBS), based on real-time brain activity, for Parkinson’s disease significantly improved motor symptoms and quality of life compared with conventional DBS.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3345-3356"},"PeriodicalIF":58.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002647","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}
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