Pub Date : 2024-07-01DOI: 10.1371/journal.pmed.1004400
Floris Bosch, Erzsébet Horváth-Puhó, Suzanne C Cannegieter, Nick van Es, Henrik T Sørensen
Background: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran.
Methods and findings: This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period.
Conclusions: In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.
背景:临床前动物实验表明,骨髓细胞合成的凝血因子X会抑制抗肿瘤免疫,而利伐沙班(一种直接Xa因子抑制剂)可用于促进肿瘤免疫。本研究旨在评估与服用直接凝血酶抑制剂达比加群的患者相比,服用直接Xa因子抑制剂的心房颤动患者罹患癌症的风险和癌症相关死亡率是否更低:这项基于丹麦全国人口的队列研究纳入了2011年至2015年间开始服用Xa因子抑制剂或达比加群且无癌症病史的成年心房颤动患者。有关病史、疗效和药物使用的数据均通过丹麦医疗登记处获得。主要结果是任何癌症。次要结果为癌症相关死亡率和全因死亡率。在意向治疗分析中,对随访 5 年的结果事件进行了评估。采用基于倾向评分的治疗逆概率加权法计算累计发病率和亚分布危险比 (SHR) 以及相应的 95% 置信区间 (CI),并将死亡作为竞争事件。采用逻辑回归法估算倾向评分,并将性别、发病日期的年龄组别、合并症和合并用药纳入模型。共纳入了11742名开始使用Xa因子抑制剂的心房颤动患者和11970名开始使用达比加群的患者。Xa 因子队列的平均年龄为 75.2 岁(标准差 [SD] 11.2),达比加群队列的平均年龄为 71.7 岁(标准差 11.1)。根据倾向得分加权模型,随访 5 年后,Xa 因子抑制剂与达比加群间的癌症累积发病率没有实质性差异(2 157/23 711;9.11%,95% CI [8.61%,9.63%])和达比加群(2,294/23,715;9.68%,95% CI [9.14%,10.25%])组之间没有观察到实质性差异(SHR 0.94,95% CI [0.89,1.00],P 值 0.0357)。我们观察到癌症相关死亡率没有差异(Xa因子抑制剂队列 1,028/23,711; 4.33%,95% CI [4.02%,4.68%]。达比加群 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]),但 Xa 因子抑制剂队列的全因死亡率较高(Xa 因子抑制剂队列 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%].达比加群 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21])。研究的主要局限性在于可能存在残余混杂因素和随访时间较短:在这项基于人群的队列研究中,与达比加群相比,Xa因子抑制剂的使用与癌症或癌症相关死亡率的总体降低无关。我们确实观察到 Xa 因子抑制剂队列中的全因死亡率有所上升。
{"title":"Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.","authors":"Floris Bosch, Erzsébet Horváth-Puhó, Suzanne C Cannegieter, Nick van Es, Henrik T Sørensen","doi":"10.1371/journal.pmed.1004400","DOIUrl":"10.1371/journal.pmed.1004400","url":null,"abstract":"<p><strong>Background: </strong>Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran.</p><p><strong>Methods and findings: </strong>This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period.</p><p><strong>Conclusions: </strong>In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477820","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 : 2024-06-25eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004423
Aaron G Lim, Nick Scott, Josephine G Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman
[This corrects the article DOI: 10.1371/journal.pmed.1003818.].
[此处更正了文章 DOI:10.1371/journal.pmed.1003818.]。
{"title":"Correction: Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.","authors":"Aaron G Lim, Nick Scott, Josephine G Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman","doi":"10.1371/journal.pmed.1004423","DOIUrl":"10.1371/journal.pmed.1004423","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pmed.1003818.].</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452018","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 : 2024-06-24eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004398
Miriam Samuel, Robin Y Park, Sophie V Eastwood, Fabiola Eto, Caroline E Morton, Daniel Stow, Sebastian Bacon, Amir Mehrkar, Jessica Morley, Iain Dillingham, Peter Inglesby, William J Hulme, Kamlesh Khunti, Rohini Mathur, Jonathan Valabhji, Brian MacKenna, Sarah Finer
<p><strong>Background: </strong>Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.</p><p><strong>Methods and findings: </strong>With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of we
{"title":"Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform.","authors":"Miriam Samuel, Robin Y Park, Sophie V Eastwood, Fabiola Eto, Caroline E Morton, Daniel Stow, Sebastian Bacon, Amir Mehrkar, Jessica Morley, Iain Dillingham, Peter Inglesby, William J Hulme, Kamlesh Khunti, Rohini Mathur, Jonathan Valabhji, Brian MacKenna, Sarah Finer","doi":"10.1371/journal.pmed.1004398","DOIUrl":"10.1371/journal.pmed.1004398","url":null,"abstract":"<p><strong>Background: </strong>Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.</p><p><strong>Methods and findings: </strong>With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of we","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447392","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 : 2024-06-24eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004329
Stephen R Walsh, Cynthia L Gay, Shelly T Karuna, Ollivier Hyrien, Timothy Skalland, Kenneth H Mayer, Magdalena E Sobieszczyk, Lindsey R Baden, Paul A Goepfert, Carlos Del Rio, Guiseppe Pantaleo, Philip Andrew, Carissa Karg, Zonglin He, Huiyin Lu, Carmen A Paez, Jane A G Baumblatt, Laura L Polakowski, Wairimu Chege, Maija A Anderson, Sophie Janto, Xue Han, Yunda Huang, Julie Dumond, Margaret E Ackerman, Adrian B McDermott, Britta Flach, Estelle Piwowar-Manning, Kelly Seaton, Georgia D Tomaras, David C Montefiori, Lucio Gama, John R Mascola
<p><strong>Background: </strong>Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.</p><p><strong>Methods and findings: </strong>Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A sing
{"title":"Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.","authors":"Stephen R Walsh, Cynthia L Gay, Shelly T Karuna, Ollivier Hyrien, Timothy Skalland, Kenneth H Mayer, Magdalena E Sobieszczyk, Lindsey R Baden, Paul A Goepfert, Carlos Del Rio, Guiseppe Pantaleo, Philip Andrew, Carissa Karg, Zonglin He, Huiyin Lu, Carmen A Paez, Jane A G Baumblatt, Laura L Polakowski, Wairimu Chege, Maija A Anderson, Sophie Janto, Xue Han, Yunda Huang, Julie Dumond, Margaret E Ackerman, Adrian B McDermott, Britta Flach, Estelle Piwowar-Manning, Kelly Seaton, Georgia D Tomaras, David C Montefiori, Lucio Gama, John R Mascola","doi":"10.1371/journal.pmed.1004329","DOIUrl":"10.1371/journal.pmed.1004329","url":null,"abstract":"<p><strong>Background: </strong>Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.</p><p><strong>Methods and findings: </strong>Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A sing","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447391","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 : 2024-06-14eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004383
Anne Ahrendt Bjerregaard, Daniel E Zoughbie, Jørgen Vinsløv Hansen, Charlotta Granström, Marin Strøm, Þórhallur Ingi Halldórsson, Inger Kristine Meder, Walter Churchill Willett, Eric L Ding, Sjúrður Fróði Olsen
Background: Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement.
Methods and findings: We conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations
背景:目前还没有发现什么具有成本效益的策略能使人们的饮食习惯向更健康的方向转变。我们研究了参与通过短信服务("SMS-program")发送的聊天机器人健康教育计划是否能改善青少年的饮食行为和体重轨迹。我们还探讨了母亲或同伴参与可能带来的额外效果:我们在丹麦国家出生队列(DNBC)的青少年中开展了一项随机对照试验(RCT)。符合条件的青少年在 2015 年至 2016 年期间,14 岁时填写了一份评估身高、体重和饮食习惯的问卷。三分之二的青少年被邀请参加短信计划,而三分之一("非短信组")的青少年则没有收到邀请。短信计划旨在改善三种主要的饮食摄入行为:含糖饮料(SSB)、水果和蔬菜(FV)以及鱼类。所提供的计划有 3 个因素随机方案;其目的是测试让母亲或朋友也参与健康促进计划的效果,以及测试为期 4 周的个人定制短信计划与针对所有 3 种膳食因素的 12 周短信计划的效果。在6个月和18个月的随访期间,通过基于智能手机的简短膳食调查问卷对身高、体重以及固态碳水化合物、固态脂肪和鱼类的摄入量进行了两次评估。主要结果测量指标为:(1)体重指数(BMI)Z 值;(2)简略健康饮食指数(mini-HEI,1 m 窗口,作为 SSB、FV 和鱼类 z 值的平均值)。在随机抽取的 7890 名青少年中,有 5260 人被分配到任何 SMS 计划中;63%(3338 人)参加了所提供的计划。在随机分配的 7890 名青少年中,分别有 74% (5853 人)和 68% (5370 人)接受了 6 个月和 18 个月的随访。通过意向治疗(ITT)分析和反向概率加权协议(IPW-PP)分析估算了效果,但不包括未参加计划的青少年。基线、6 米和 18 米时的迷你 HEI 平均值(标准差 (SD))分别为 -0.01 (0.64)、0.01 (0.59) 和 -0.01 (0.59)。在 ITT 分析中,与未接受短信服务的人群相比,接受过任何短信服务的人群在任何时间点均未观察到对体重指数 z 值的影响(6 m:-0.010 [95% 置信区间 (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901)或迷你 HEI(6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18 m: -0.016 [95% CI -0.045, 0.013]; p = 0.286)。在 IPW-PP 分析中,在 6 m 时,观察到接受过任何 SMS 计划的人群与未接受过任何 SMS 计划的人群相比,体重指数 z 值略有下降(-0.030 [95% CI -0.057, -0.003];p = 0.032),而在迷你 HEI(0.027 [95% CI -0.002, 0.056];p = 0.072)方面未观察到显著影响。在 18 米处,未观察到任何关联(体重指数 z 值:-0.006 [95% CI -0.039, 0.027];p = 0.724;迷你 HEI:-0.005 [95% CI -0.036, 0.026];p = 0.755)。研究的主要局限性在于,DNBC 参与者虽然来自普通人群,但其社会经济地位往往高于平均水平,而且结果测量是自我报告的:在这项研究中,通过短信程序提供的聊天机器人健康教育计划在 ITT 分析中对饮食习惯或体重轨迹没有影响。未来的研究应侧重于开发针对不同性别的信息计划,包括 "助推 "信息,以获得持续的参与:临床试验注册:ClinicalTrials.gov Identifier:NCT02809196 https://clinicaltrials.gov/study/NCT02809196。
{"title":"An SMS chatbot digital educational program to increase healthy eating behaviors in adolescence: A multifactorial randomized controlled trial among 7,890 participants in the Danish National Birth Cohort.","authors":"Anne Ahrendt Bjerregaard, Daniel E Zoughbie, Jørgen Vinsløv Hansen, Charlotta Granström, Marin Strøm, Þórhallur Ingi Halldórsson, Inger Kristine Meder, Walter Churchill Willett, Eric L Ding, Sjúrður Fróði Olsen","doi":"10.1371/journal.pmed.1004383","DOIUrl":"10.1371/journal.pmed.1004383","url":null,"abstract":"<p><strong>Background: </strong>Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service (\"SMS-program\") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement.</p><p><strong>Methods and findings: </strong>We conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 (\"non-SMS group\") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321900","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 : 2024-06-10eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004414
Gladymar Pérez Chacón, Marie J Estcourt, James Totterdell, Julie A Marsh, Kirsten P Perrett, Dianne E Campbell, Nicholas Wood, Michael Gold, Claire S Waddington, Michael O' Sullivan, Sonia McAlister, Nigel Curtis, Mark Jones, Peter B McIntyre, Patrick G Holt, Peter C Richmond, Tom Snelling
Background: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.
Methods and findings: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction r
背景:在许多国家,婴儿接种无细胞百日咳(aP)疫苗已取代了反应性更强的全细胞百日咳(wP)疫苗。根据免疫学和流行病学证据,我们假设用 wP 疫苗代替常规接种计划中的第一剂 aP 疫苗可能会预防 IgE 介导的食物过敏。我们的目的是比较 wP/aP 混合接种方案与纯 aP 标准接种方案的反应原性、免疫原性和 IgE 介导的反应:OPTIMUM 是一项贝叶斯、两阶段、双盲、随机试验。在第一阶段,婴儿在约 6 周大时被分配(1:1)接种第一剂五价 wP 混合疫苗(DTwP-Hib-HepB,Pentabio PT Bio Farma,印度尼西亚)或六价 aP 疫苗(DTaP-Hib-HepB-IPV,Infanrix hexa,葛兰素史克,澳大利亚)。随后,所有婴儿在 4 个月和 6 个月大时接种六价 aP 疫苗,并在 18 个月大时接种 aP 疫苗(DTaP-IPV,Infanrix-IPV,澳大利亚葛兰素史克公司)。第二阶段正在进行中,采用上述随机策略和疫苗接种计划。在确定12个月大时由过敏症专家确诊的IgE介导的食物过敏这一主要临床结果之前,我们在此介绍次要免疫原性、反应原性、破伤风类毒素IgE介导的免疫反应和家长接受度终点的结果。血清中对白喉、破伤风和百日咳抗原的 IgG 反应是通过多重荧光珠免疫测定法测定的;血浆中的总 IgE 和特异性 IgE 是通过 ImmunoCAP 测定法(赛默飞世尔科技公司)测定的。混合方案的免疫原性被定义为不劣于纯百日咳方案的免疫原性,其非劣性差值为百日咳方案6个月后1个月百日咳毒素(PT)-IgG几何平均浓度(GMR)比值的2/3。按研究臂对征求到的不良反应进行汇总,包括所有接受首剂 wP 或 aP 的儿童。家长的接受程度采用 5 点李克特量表进行评估。主要分析以意向治疗(ITT)为基础,同时还进行了每方案(PP)次要分析。该试验已在 ANZCTR 注册(ACTRN12617000065392p)。2018年3月7日至2020年1月13日期间,150名婴儿接受了随机治疗(每组75名)。6个月aP剂量后约1个月时,混合方案的PT-IgG反应不劣于纯aP方案[GMR=0-98,95%可信区间(0-77至1-26);概率(GMR>2/3)>0-99;ITT分析]。7 个月大时,混合方案组和纯 aP 组破伤风类毒素 IgE 定量的后中位概率均为 0-22(95% 可信区间为 0-12 至 0-34)。尽管排除了其他因素,但 PP 分析的结果是一致的。6周大时,烦躁是wP组(74人中有65人[88%])和aP组(72人中有59人[82%])接种者最常见的全身性诱发反应。在同一年龄段,接种 wP 疫苗的 74 名婴儿中有 14 名(19%)出现了严重的全身反应,接种 aP 疫苗的 72 名婴儿中有 8 名(11%)出现了严重的全身反应。在最初 6 个月的随访中,有 5 名参与者发生了 7 例 SAE;经过盲法评估,没有发现任何与研究疫苗有关的情况。家长对混合接种和纯 aP 接种方案的接受度很高(73 名家长中有 71 人 [97%] 同意再次接种相同的接种方案,72 名家长中有 69 人 [96%] 同意再次接种相同的接种方案)。结论 与纯 aP 方案相比,混合方案引起的 PT-IgG 反应并不差,但反应更严重,但家长接受度高。各研究组的破伤风类毒素 IgE 反应没有差异:试验在澳大利亚和新西兰临床 207 试验注册中心注册(ACTRN12617000065392p)。https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371998&isReview=true。只有一个登记处(同上)。
{"title":"Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.","authors":"Gladymar Pérez Chacón, Marie J Estcourt, James Totterdell, Julie A Marsh, Kirsten P Perrett, Dianne E Campbell, Nicholas Wood, Michael Gold, Claire S Waddington, Michael O' Sullivan, Sonia McAlister, Nigel Curtis, Mark Jones, Peter B McIntyre, Patrick G Holt, Peter C Richmond, Tom Snelling","doi":"10.1371/journal.pmed.1004414","DOIUrl":"10.1371/journal.pmed.1004414","url":null,"abstract":"<p><strong>Background: </strong>In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.</p><p><strong>Methods and findings: </strong>OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction r","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301964","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}
Background: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age.
Methods and findings: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring.
Conclusions: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.
{"title":"Metabolic profiles of children aged 2-5 years born after frozen and fresh embryo transfer: A Chinese cohort study.","authors":"Wei Zhou, Wanbing Feng, Jinli Chang, Jingmei Hu, Fuxia Li, Kuona Hu, Jiejing Jiao, Xinyi Xue, Ting Lan, Wenjing Wan, Zi-Jiang Chen, Linlin Cui","doi":"10.1371/journal.pmed.1004388","DOIUrl":"10.1371/journal.pmed.1004388","url":null,"abstract":"<p><strong>Background: </strong>Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age.</p><p><strong>Methods and findings: </strong>This was a prospective cohort study. Using data from the \"Assisted Reproductive Technology borned KIDs (ARTKID),\" a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring.</p><p><strong>Conclusions: </strong>In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285094","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 : 2024-06-03eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004335
Mohammed K Ali, Kavita Singh, Dimple Kondal, Raji Devarajan, Shivani A Patel, V Usha Menon, Premlata K Varthakavi, Vijay Vishwanathan, Mala Dharmalingam, Ganapati Bantwal, Rakesh Kumar Sahay, Muhammad Qamar Masood, Rajesh Khadgawat, Ankush Desai, Dorairaj Prabhakaran, K M Venkat Narayan, Nikhil Tandon
Background: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial.
Methods and findings: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascul
{"title":"Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.","authors":"Mohammed K Ali, Kavita Singh, Dimple Kondal, Raji Devarajan, Shivani A Patel, V Usha Menon, Premlata K Varthakavi, Vijay Vishwanathan, Mala Dharmalingam, Ganapati Bantwal, Rakesh Kumar Sahay, Muhammad Qamar Masood, Rajesh Khadgawat, Ankush Desai, Dorairaj Prabhakaran, K M Venkat Narayan, Nikhil Tandon","doi":"10.1371/journal.pmed.1004335","DOIUrl":"10.1371/journal.pmed.1004335","url":null,"abstract":"<p><strong>Background: </strong>Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial.</p><p><strong>Methods and findings: </strong>This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascul","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238585","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 : 2024-06-03eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004375
Amanda Jane Leach, Nicole Wilson, Beth Arrowsmith, Jemima Beissbarth, Kim Mulholland, Mathuram Santosham, Paul John Torzillo, Peter McIntyre, Heidi Smith-Vaughan, Sue A Skull, Victor M Oguoma, Mark D Chatfield, Deborah Lehmann, Christopher G Brennan-Jones, Michael J Binks, Paul V Licciardi, Ross M Andrews, Tom Snelling, Vicki Krause, Jonathan Carapetis, Anne B Chang, Peter Stanley Morris
Background: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations.
Methods and findings: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size.
Conclusions: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation.
Trial registration: ClinicalTrials.gov NCT01735084 and NCT01174849.
{"title":"Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.","authors":"Amanda Jane Leach, Nicole Wilson, Beth Arrowsmith, Jemima Beissbarth, Kim Mulholland, Mathuram Santosham, Paul John Torzillo, Peter McIntyre, Heidi Smith-Vaughan, Sue A Skull, Victor M Oguoma, Mark D Chatfield, Deborah Lehmann, Christopher G Brennan-Jones, Michael J Binks, Paul V Licciardi, Ross M Andrews, Tom Snelling, Vicki Krause, Jonathan Carapetis, Anne B Chang, Peter Stanley Morris","doi":"10.1371/journal.pmed.1004375","DOIUrl":"10.1371/journal.pmed.1004375","url":null,"abstract":"<p><strong>Background: </strong>In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations.</p><p><strong>Methods and findings: </strong>In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size.</p><p><strong>Conclusions: </strong>In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT01735084 and NCT01174849.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238587","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 : 2024-06-03eCollection Date: 2024-06-01DOI: 10.1371/journal.pmed.1004413
A J Lowik, Caroline Mniszak, Michelle Pang, Kimia Ziafat, Mohammad Karamouzian, Rod Knight
Background: While there is widespread consensus that sex- and gender-related factors are important for how interventions are designed, implemented, and evaluated, it is not currently known how alcohol treatment research accounts for sex characteristics and/or gender identities and modalities. This methodological systematic review documents and assesses how sex characteristics, gender identities, and gender modalities are operationalized in alcohol treatment intervention research involving youth.
Methods and findings: We searched MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, PsycINFO, CINAHL, LGBT Life, Google Scholar, Web of Science, and grey literature from 2008 to 2023. We included articles that reported genders and/or sexes of participants 30 years of age and under and screened participants using AUDIT, AUDIT-C, or a structured interview using DSM-IV criteria. We limited the inclusion to studies that enrolled participants in alcohol treatment interventions and used a quantitative study design. We provide a narrative overview of the findings. Of 8,019 studies screened for inclusion, 86 articles were included in the review. None of the studies defined, measured, and reported both sex and gender variables accurately. Only 2 studies reported including trans participants. Most of the studies used gender or sex measures as a covariate to control for the effects of sex or gender on the intervention but did not discuss the rationale for or implications of this procedure.
Conclusions: Our findings identify that the majority of alcohol treatment intervention research with youth conflate sex and gender factors, including terminologically, conceptually, and methodologically. Based on these findings, we recommend future research in this area define and account for a spectrum of gender modalities, identities, and/or sex characteristics throughout the research life cycle, including during study design, data collection, data analysis, and reporting. It is also imperative that sex and gender variables are used expansively to ensure that intersex and trans youth are meaningfully integrated.
背景:尽管人们普遍认为与性和性别相关的因素对于干预措施的设计、实施和评估非常重要,但目前还不清楚酒精治疗研究是如何考虑性别特征和/或性别认同和模式的。本方法论系统性综述记录并评估了在涉及青少年的酒精治疗干预研究中如何操作性特征、性别认同和性别模式:我们检索了 2008 年至 2023 年间的 MEDLINE、Embase、Cochrane Central Registry of Controlled Trials、PsycINFO、CINAHL、LGBT Life、Google Scholar、Web of Science 和灰色文献。我们收录了那些报告了 30 岁及以下参与者的性别,并使用 AUDIT、AUDIT-C 或使用 DSM-IV 标准的结构化访谈对参与者进行筛查的文章。我们仅限于纳入酒精治疗干预并采用定量研究设计的研究。我们对研究结果进行了叙述性概述。在筛选出的 8,019 项研究中,有 86 篇文章被纳入综述。这些研究均未准确定义、测量和报告性与性别变量。只有 2 项研究报告了变性参与者。大多数研究使用性别或性测量作为协变量来控制性或性别对干预的影响,但没有讨论这一程序的原理或影响:我们的研究结果表明,大多数针对青少年的酒精治疗干预研究都混淆了性和性别因素,包括术语、概念和方法上的混淆。基于这些发现,我们建议今后在这一领域的研究在整个研究生命周期中,包括在研究设计、数据收集、数据分析和报告过程中,对各种性别模式、身份和/或性别特征进行定义和说明。此外,还必须广泛使用性和性别变量,以确保将双性青年和变性青年有意义地纳入其中:注册:注册:PROSPERO,注册号:CRD42019119408:CRD42019119408。
{"title":"A sex- and gender-based analysis of alcohol treatment intervention research involving youth: A methodological systematic review.","authors":"A J Lowik, Caroline Mniszak, Michelle Pang, Kimia Ziafat, Mohammad Karamouzian, Rod Knight","doi":"10.1371/journal.pmed.1004413","DOIUrl":"10.1371/journal.pmed.1004413","url":null,"abstract":"<p><strong>Background: </strong>While there is widespread consensus that sex- and gender-related factors are important for how interventions are designed, implemented, and evaluated, it is not currently known how alcohol treatment research accounts for sex characteristics and/or gender identities and modalities. This methodological systematic review documents and assesses how sex characteristics, gender identities, and gender modalities are operationalized in alcohol treatment intervention research involving youth.</p><p><strong>Methods and findings: </strong>We searched MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, PsycINFO, CINAHL, LGBT Life, Google Scholar, Web of Science, and grey literature from 2008 to 2023. We included articles that reported genders and/or sexes of participants 30 years of age and under and screened participants using AUDIT, AUDIT-C, or a structured interview using DSM-IV criteria. We limited the inclusion to studies that enrolled participants in alcohol treatment interventions and used a quantitative study design. We provide a narrative overview of the findings. Of 8,019 studies screened for inclusion, 86 articles were included in the review. None of the studies defined, measured, and reported both sex and gender variables accurately. Only 2 studies reported including trans participants. Most of the studies used gender or sex measures as a covariate to control for the effects of sex or gender on the intervention but did not discuss the rationale for or implications of this procedure.</p><p><strong>Conclusions: </strong>Our findings identify that the majority of alcohol treatment intervention research with youth conflate sex and gender factors, including terminologically, conceptually, and methodologically. Based on these findings, we recommend future research in this area define and account for a spectrum of gender modalities, identities, and/or sex characteristics throughout the research life cycle, including during study design, data collection, data analysis, and reporting. It is also imperative that sex and gender variables are used expansively to ensure that intersex and trans youth are meaningfully integrated.</p><p><strong>Trial registration: </strong>Registration: PROSPERO, registration number: CRD42019119408.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238584","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}