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Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study. 确诊糖耐量受损后的非糖尿病状态与长期死亡和血管并发症的风险:大庆糖尿病预防结果研究的事后分析。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-07-09 eCollection Date: 2024-07-01 DOI: 10.1371/journal.pmed.1004419
Xin Qian, Jinping Wang, Qiuhong Gong, Yali An, Xinxing Feng, Siyao He, Xiaoping Chen, Wenjuan Wang, Lihong Zhang, Yuanchi Hui, Xiuwei Zhai, Bo Zhang, Yanyan Chen, Guangwei Li

Background: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified.

Methods and findings: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population.

Conclusions: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

背景:糖耐量减低症(IGT)确诊后未患糖尿病的年数与长期死亡和心血管疾病风险之间的关系需要明确:糖耐量减低症(IGT)确诊后的非糖尿病状态年限与长期死亡和心血管疾病风险之间的关系需要明确:在这项事后分析中,我们纳入了参与最初的大庆糖尿病预防研究(DQDPS)的540名IGT患者。在大庆糖尿病预防研究中,所有参与者均通过 75 克口服葡萄糖耐量试验确诊为 IGT,并随机分为干预组和对照组,进行为期 6 年的生活方式干预试验。试验结束后,对死亡、心血管事件和微血管并发症进行了长达30年的随访监测。在这项事后分析中,Cox 分析评估了在确诊 IGT 后 2 年、4 年和 6 年末,保持非糖尿病状态或发展为糖尿病的个体发生这些结果的扩展风险。在所有参与者中,糖尿病组和非糖尿病组之间的结果累积发生率差异在30年内逐渐增大。与糖尿病组相比,全因死亡风险明显降低(危险比 [HR]:0.74; 95% 置信区间 [CI]:与糖尿病组相比,全因死亡风险(危险比 [HR]:0.74;95% 置信区间 [CI]:0.57 至 0.97,p = 0.026)、心血管事件(HR:0.63;95% CI:0.49 至 0.82,p < 0.001)和微血管并发症(HR:0.62;95% CI:0.45 至 0.86,p = 0.004)的显著降低首先出现在 4 年访视时仍未患糖尿病的人群中,而心血管死亡风险的显著降低则首次出现在 6 年末(HR:0.56; 95% CI: 0.39 to 0.81, p = 0.002),这是在调整了年龄、性别、吸烟状况、体重指数、收缩压、血糖、总胆固醇、干预措施和药物(包括胰岛素加口服降糖药、降压药和降脂药)之后得出的结果。原干预组的结果与全组相似。我们研究的主要局限性在于参与者人数有限,而且只有中国人:在这项研究中,我们观察到在确诊 IGT 后维持数年的非糖尿病状态与显著降低死亡和血管并发症的长期风险有关。
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引用次数: 0
Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial. 瑞典改变妊娠糖尿病诊断标准(CDC4G):阶梯楔形分组随机试验。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-07-08 eCollection Date: 2024-07-01 DOI: 10.1371/journal.pmed.1004420
Maryam de Brun, Anders Magnuson, Scott Montgomery, Snehal Patil, David Simmons, Kerstin Berntorp, Stefan Jansson, Ulla-Britt Wennerholm, Anna-Karin Wikström, Helen Strevens, Fredrik Ahlsson, Verena Sengpiel, Erik Schwarcz, Elisabeth Storck-Lindholm, Martina Persson, Kerstin Petersson, Linda Ryen, Carina Ursing, Karin Hildén, Helena Backman
<p><strong>Background: </strong>The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.</p><p><strong>Methods and findings: </strong>A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.</p><p><strong>Conclusions: </strong>In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pr
背景:世界卫生组织(WHO)2013年妊娠糖尿病(GDM)诊断标准受到了批评,因为从以前较高的血糖阈值转换到较低的WHO-2013年诊断标准时,不同人群的妊娠结局获益证据有限。本研究旨在确定,在瑞典,基于风险因素的筛查后,从以前的瑞典血糖阈值(SWE-GDM)转换为WHO-2013 GDM标准是否能改善妊娠结局:2018年1月1日至12月31日期间,在瑞典全国11个集群(17个分娩单位)进行了阶梯式楔形集群随机试验,包括所有接受护理的妊娠,并将原有糖尿病、胃旁路手术或多胎妊娠排除在分析之外。在实施统一的临床和实验室指南后,从2018年2月到11月,每月都有一些群组被随机干预(改用WHO-2013 GDM标准)。主要结果是胎龄过大(LGA,定义为出生体重大于第90百分位数)。其他次要和预设结果包括产妇和新生儿出生并发症。主要分析采用修正的意向治疗(mITT)方法,排除了在研究开始前已随机分组但无法实施干预的3个群组。对GDM定义不一致的人群进行了预设亚组分析。多层次混合回归模型用于比较 WHO-2013 组和 SWE-GDM 组之间的 LGA 结果,并对组群、时间段和潜在混杂因素进行了调整。对缺失的潜在混杂变量采用多重估算。在 mITT 分析中,共纳入了 47 080 例妊娠,进行了 6 882 次(14.6%)口服葡萄糖耐量试验(OGTT)。干预后,GDM 患病率从 595/22 797(2.6%)增至 1 591/24 283(6.6%)。在 mITT 人群中,换药与主要结果 LGA(2 790/24 209 (11.5%) 对 2 584/22 707 (11.4%))的变化无关,调整风险比 (aRR) 为 0.97(95% 置信区间为 0.91 至 1.02,p = 0.26)。在亚组中,换药前 LGA 患病率为 273/956 (28.8%),换药后为 278/1 239 (22.5%),调整风险比为 0.87 (95% CI 0.75 至 1.01,p = 0.076)。无严重事件报告。这项试验的潜在局限性主要在于试验设计,包括在群组内和群组间未能遵守指南,以及不明时间变化的影响:在这项研究中,在瑞典实施WHO-2013标准并进行基于风险因素的筛查,无论是在总人口中,还是在GDM定义不一致的亚组中,都没有显著降低出生体重大于90百分位数的LGA患病率。今后还需要开展研究,评估在不同人群中采用不同的血糖阈值、不同的筛查策略和临床管理指南对妊娠期妇女和儿童健康的短期和长期优化效果:该试验已在 ISRCTN(41918550)上注册。
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引用次数: 0
Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis. 评估美国男男性行为者淋病经验性治疗应改变的抗药性流行阈值:成本效益分析。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-07-08 eCollection Date: 2024-07-01 DOI: 10.1371/journal.pmed.1004424
Xuecheng Yin, Yunfei Li, Minttu M Rönn, Song Li, Yue Yuan, Thomas L Gift, Katherine Hsu, Joshua A Salomon, Yonatan H Grad, Reza Yaesoubi

Background: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea.

Methods and findings: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy.

Conclusions: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

背景:由于淋病的普通诊断检测无法提供对抗生素的敏感性信息,因此淋病的治疗仍然是经验疗法。一旦耐药率超过一定阈值(如 5%),通常会更换用于经验疗法的抗生素。较低的换药阈值旨在提高使用一线抗生素成功治疗感染的概率,但同时也会加快建议换用较新抗生素的速度。人们对改变换药阈值对淋病发病率、治疗失败率以及与淋病相关的总体成本和质量调整生命年(QALYs)的影响知之甚少:我们建立了一个多耐药菌株淋球菌感染的传播模型,以预测在美国男男性行为者(MSM)中不同转换阈值下与淋病相关的成本和 QALYs 损失。我们考虑了与症状、诊断、治疗和后遗症相关的成本和损耗,并将成本和 QALYs 合并为净健康效益 (NHB)。我们的研究结果表明,在未来 50 年内有 3 种抗生素可用(2 种适用于淋病的一线治疗,1 种仅适用于耐药感染的再治疗)的情况下,改变 1%-10%之间的转换阈值不会对淋病的年病例数、总成本或与淋病相关的总 QALY 损失产生有意义的影响。不过,如果将来有新的抗生素上市,选择较低的转换阈值可能会改善人群 NHB。此外,如果药物敏感性检测(DST)可以为一线治疗失败后的再治疗方案提供依据,那么将转换阈值设定在 1%-2%之间有望最大限度地提高人群的 NHB。我们研究的局限性在于,我们的分析仅关注 MSM 群体,并未考虑疫苗等干预措施的影响,也未考虑常用快速药敏试验为一线治疗提供依据:结论:改变一线抗生素的转换阈值可能不会大幅改变与淋病相关的健康和财务结果。然而,如果新型抗生素有望很快上市,或者除了未来的新型抗生素外,DST 也能为再治疗方案提供依据,则可以降低转换阈值。
{"title":"Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.","authors":"Xuecheng Yin, Yunfei Li, Minttu M Rönn, Song Li, Yue Yuan, Thomas L Gift, Katherine Hsu, Joshua A Salomon, Yonatan H Grad, Reza Yaesoubi","doi":"10.1371/journal.pmed.1004424","DOIUrl":"10.1371/journal.pmed.1004424","url":null,"abstract":"<p><strong>Background: </strong>Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea.</p><p><strong>Methods and findings: </strong>We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy.</p><p><strong>Conclusions: </strong>Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004424"},"PeriodicalIF":15.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560102","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}
引用次数: 0
Association between achieving adequate antenatal care and health-seeking behaviors: A study of Demographic and Health Surveys in 47 low- and middle-income countries. 实现充分的产前保健与寻求健康行为之间的关系:47 个中低收入国家的人口与健康调查研究。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-07-05 eCollection Date: 2024-07-01 DOI: 10.1371/journal.pmed.1004421
Boshen Jiao, Isabelle Iversen, Ryoko Sato, Clint Pecenka, Sadaf Khan, Ranju Baral, Margaret E Kruk, Catherine Arsenault, Stéphane Verguet

Background: Antenatal care (ANC) is essential for ensuring the well-being of pregnant women and their fetuses. This study models the association between achieving adequate ANC and various health and health-seeking indicators across wealth quintiles in low- and middle-income countries (LMICs).

Methods and findings: We analyzed data from 638,265 women across 47 LMICs using available Demographic and Health Surveys from 2010 to 2022. Via multilevel logistic regression analyses adjusted for a series of confounding variables and country and wealth quintile fixed effects, we estimated the projected impact of achieving adequate ANC utilization and quality on a series of health and health care indicators: facility birth, postnatal care, childhood immunizations, and childhood stunting and wasting. Achieving adequate levels of ANC utilization and quality (defined as at least 4 visits, blood pressure monitoring, and blood and urine testing) was positively associated with health-seeking behavior across the majority of countries. The strongest association was observed for facility birth, followed by postnatal care and child immunization. The strength of the associations varied across countries and wealth quintiles, with more significant ones observed in countries with lower baseline ANC utilization levels and among the lower wealth quintiles. The associations of ANC with childhood stunting and wasting were notably less statistically significant compared to other indicators. Despite rigorous adjustments for potential confounders, a limitation to the methodology is that it is possible that unobserved variables may still impact outcomes.

Conclusions: Strengthening ANC is associated with improved use of other health care in LMICs. ANC could serve as a critical platform for improving health outcomes for mothers and their children, emphasizing its importance beyond direct impact on maternal and neonatal mortality.

背景:产前保健(ANC)对确保孕妇及其胎儿的健康至关重要。本研究模拟了中低收入国家(LMICs)不同财富五分位数的孕妇获得适当的产前保健与各种健康和寻求健康指标之间的关系:我们利用 2010 年至 2022 年的人口与健康调查,分析了 47 个中低收入国家 638,265 名妇女的数据。通过对一系列混杂变量以及国家和财富五分位数固定效应进行调整的多层次逻辑回归分析,我们估算了实现充足的产前护理利用率和质量对一系列健康和医疗指标的预期影响:设施内分娩、产后护理、儿童免疫接种以及儿童发育迟缓和消瘦。在大多数国家,产前护理利用率和质量达到适当水平(定义为至少 4 次就诊、血压监测、血液和尿液检测)与寻求保健行为呈正相关。设施接生的关联性最强,其次是产后护理和儿童免疫接种。不同国家和财富五分位数之间的关联强度各不相同,基线产前护理利用水平较低的国家和财富五分位数较低的国家的关联强度更大。与其他指标相比,产前保健与儿童发育迟缓和消瘦的相关性在统计意义上明显较低。尽管对潜在的混杂因素进行了严格调整,但该方法的局限性在于,未观察到的变量仍有可能对结果产生影响:结论:在低收入国家,加强产前保健与改善其他医疗保健的使用有关。产前护理可作为改善母婴健康结果的重要平台,其重要性超出了对孕产妇和新生儿死亡率的直接影响。
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引用次数: 0
Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study. Xa 直接因子抑制剂与癌症风险和癌症死亡率:一项基于丹麦人口的队列研究。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-07-01 DOI: 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":"21 7","pages":"e1004400"},"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}
引用次数: 0
Correction: Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis. 更正:在巴基斯坦消除丙型肝炎病毒的健康和经济效益:模型研究和经济分析。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-06-25 eCollection Date: 2024-06-01 DOI: 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.]。
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引用次数: 0
Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform. 在冠状病毒-19 大流行之前和期间,英国初级保健记录的体重增加趋势:使用 OpenSAFELY 平台进行的观察性队列研究。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-06-24 eCollection Date: 2024-06-01 DOI: 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
背景:肥胖和体重快速增长是非传染性疾病的既定风险因素,也是感染冠状病毒病 2019(COVID-19)后导致严重疾病的独立风险因素。为减少 COVID-19 传播而实施的限制措施导致了深刻的社会变化,影响了许多与体重增加速度相关的健康行为,包括体育锻炼和营养。我们调查了在 COVID-19 大流行期间,在英国国民健康服务系统(NHS)全科医生处登记的成年人中,哪些临床和社会人口特征与体重快速增长和体重增长速度最大有关:经英格兰国家医疗服务系统(NHS)批准,我们使用 TPP 内的 OpenSAFELY 平台对常规收集的电子医疗记录进行了观察性队列研究。我们调查了 2015 年 3 月至 2022 年 3 月期间英国初级医疗记录中身体质量指数 (BMI) 值的变化。我们提取了在英国初级医疗机构注册的 17742365 名 18 至 90 岁成年人(50.1% 为女性,76.1% 为英国白人)的数据。我们估算了大流行前(δ-大流行前)和大流行期间(δ-大流行期间)的个人体重增加率,并确定了每个时期体重增加过快(>0.5 kg/m2/年)的个人。我们还估算了大流行前和大流行期间体重增加率的变化(δ-变化 = δ-大流行-δ-大流行前),并将极端加速者定义为在这两个时期之间体重增加率增幅最大(δ-变化≥1.84 kg/m2/年)的 10%的个体。我们使用多变量逻辑回归法估计了这些结果与年龄、性别、多重贫困指数(IMD)和种族的关系。回归模型中产生了 P 值。我们研究人群的体重指数中位数在 2019 年(2019 年 3 月至 2020 年 2 月)为 27.8 kg/m2,四分位数间距 (IQR) [24.3, 32.1];在 2021 年为 28.0 kg/m2,IQR [24.4, 32.6]。大流行期间体重快速增长与性别、年龄和 IMD 有关。0.60,95% 置信区间 [0.60,0.61],p <0.001]);生活在较贫困地区(最不贫困五分位数与最贫困五分位数:aOR 0.77,95% 置信区间 [0.77,0.78],p <0.001)会降低体重快速增加的几率。与英国白人相比,所有其他种族的人体重快速增长的几率较低(例如,印度人与英国白人相比:aOR 0.69,95% CI [0.68,0.70],p <0.001)。长期病症(LTCs)会增加几率,其中精神健康状况的影响最大(如抑郁症(aOR 1.18,95% CI [1.17,1.18],p < 0.001))。类似的特征增加了大流行前和大流行期间体重增加速度极度加快的几率。然而,大流行期间医疗保健活动的变化可能会给数据带来新的偏差:我们发现,女性性别、年轻、贫困、英国白人种族和精神健康状况与大流行前和大流行期间体重迅速增加和体重增加速度极度加快有关。我们的研究结果突出表明,在大流行后服务恢复期和未来大流行规划中,在制定针对体重指数的研究、政策和干预措施时,有必要纳入社会人口、身体和心理健康特征。
{"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;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 (&gt;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 &lt; 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 &lt; 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 &lt; 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 &lt; 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 &lt; 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of we","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 6","pages":"e1004398"},"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}
引用次数: 0
Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial. 通过不同途径和剂量给药的 VRC07-523LS 的安全性和药代动力学(HVTN 127/HPTN 087):一期随机临床试验。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-06-24 eCollection Date: 2024-06-01 DOI: 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
背景:广谱中和抗体(bnAbs)是一种很有前景的 HIV-1 预防方法。在抗体介导的预防(AMP)试验中,一种以 CD4 结合位点为靶点的 bnAb(VRC01)经静脉注射(IV)后,对中和敏感性高的病毒有 75% 的预防效果,但对敏感性较低的病毒无效。VRC07-523LS 是以 CD4 结合位点为靶点的新一代 bnAb,其设计可提高中和广度和半衰期。我们开展了一项多中心、随机、部分盲法的 I 期临床试验,以评估 VRC07-523LS 的安全性和血清浓度:参与者招募时间为 2018 年 2 月 2 日至 2018 年 10 月 9 日。共有 124 名参与者被随机分配到通过静脉注射(T1:2.5 mg/kg,T2:5 mg/kg,T3:20 mg/kg)、皮下注射(SC)(T4:2.5 mg/kg,T5:5 mg/kg)或肌内注射(IM)(T6:2.5 mg/kg或P6:安慰剂)途径接受 5 次 VRC07-523LS 给药,间隔时间为 4 个月。对于IM组的VRC07-523LS与安慰剂,参与者和研究机构的工作人员均为盲人,而所有其他剂量和途径均为开放标签。在首次给药后的 144 周内收集了安全性数据。所有参与者的 VRC07-523LS 血清浓度在第 112 天之前通过 ELISA 法进行测量,之后在第 784 天之前通过结合抗体多重测定法 (BAMA) 对 60 名参与者(每个治疗组 10 人)进行测量。为评估 VRC07-523LS 血清 PK,进行了区组群体药代动力学 (PK) 分析。中和活性通过 TZM-bl 试验测定,抗药抗体 (ADAs) 通过分层桥接试验策略测定。注射和输液的耐受性良好,SC 组和 IM 组常见轻度疼痛或触痛,SC 组常见轻度至中度红斑或压痕。在 20 毫克/千克静脉注射组的 20 名参与者中,有 3 人出现输液反应。首次给药后的峰值几何平均(GM)浓度(95% 置信区间 [95% CIs])分别为 29.0 μg/mL(25.2, 33.4)、58.5 μg/mL(49.4, 69.3)和 257.T1-T3采用静脉给药,为10.8 μg/mL(8.8,13.3)和22.8 μg/mL(20.1,25.9);T6采用IM给药,为16.4 μg/mL(14.7,18.2)。第二次给药前的最低 GM 浓度(95% CIs)分别为 3.4 μg/mL (2.5, 4.6)、6.5 μg/mL (5.6, 7.5) 和 27.静脉注射时为 0.97 μg/mL (0.65, 1.4) 和 3.1 μg/mL (2.2, 4.3),IM 注射时为 2.6 μg/mL (2.05, 3.31)。VRC07-523LS 的血清浓度峰值随给药剂量呈线性增长。在给定剂量下,静脉注射组的峰值和谷值浓度以及血清中和滴度最高,反映出静脉注射和间歇给药的生物利用度较低。在一个单独的时间点上,发现一名参试者的 ADA 滴度较低。在所有剂量和途径中,VRC07-523LS的平均半衰期估计为42天(95% CI:40.5, 43.5),是VRC01(15天)的两倍多:结论:VRC07-523LS在各种剂量和途径下均安全且耐受性良好,是一种很有希望纳入HIV-1预防方案的长效bnAb:试验注册:ClinicalTrials.gov/ NCT03387150(2017年12月21日发布)。
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引用次数: 0
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. 短信聊天机器人数字教育计划,旨在提高青少年的健康饮食行为:在丹麦全国出生队列的 7890 名参与者中开展的多因素随机对照试验。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-06-14 eCollection Date: 2024-06-01 DOI: 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。
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引用次数: 0
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. 澳大利亚婴儿接种全细胞和无细胞百日咳混合疫苗的免疫原性、反应性和 IgE 介导的免疫反应:随机、双盲、非劣效试验。
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2024-06-10 eCollection Date: 2024-06-01 DOI: 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)。
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