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Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study 在美国,华法林与直接口服抗凝剂治疗癌症相关静脉血栓栓塞的生存结果比较:一项基于人群的队列研究
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1004012
Adeela Khan, T. Chiasakul, R. Redd, R. Patell, E. McCarthy, D. Neuberg, J. Zwicker
Background Direct oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established. Methods and findings Utilizing the United States’ Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied. Conclusions In this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.
直接口服抗凝剂(DOACs)在治疗癌症相关静脉血栓栓塞(VTE)方面与低分子肝素(LMWH)具有相当的疗效。与华法林相比,DOACs在治疗癌症静脉血栓栓塞(VTE)方面是否有死亡率优势尚不确定。方法和研究结果利用2012年至2016年美国监测、流行病学和最终结果(SEER)-Medicare相关数据库,我们分析了在静脉血栓栓塞诊断后30天内接受DOAC或华法林处方的原发性胃癌、结肠直肠癌、胰腺癌、肺癌、卵巢癌或脑癌和静脉血栓栓塞患者的总生存率。通过癌症分期的精确匹配和年龄、癌症部位、癌症分期、从癌症到VTE诊断的时间间隔的倾向评分匹配,对患者进行1:2 (DOAC与华法林)匹配。该分析确定了4274例在癌症诊断后30天内接受DOAC或华法林治疗静脉血栓栓塞的患者(DOAC组1348例,华法林组2926例)。患者中位年龄为75岁,56%为女性。在DOAC组中,1188例(88%)接受利伐沙班治疗,160例(12%)接受阿哌沙班治疗。中位随访时间为41个月,与DOACs相比,华法林与统计学上显著更高的总生存期相关(中位总生存期12.0个月[95%可信区间(CI): 10.9至13.5]对9.9个月[95% CI: 8.4至11.2];风险比(HR) 0.85;95% CI: 0.78 ~ 0.91;P < 0.001)。观察到的生存差异在癌症部位、癌症分期和静脉血栓栓塞类型的亚组中是一致的。该研究的局限性包括回顾性设计,可能存在未解释的混杂因素,以及所研究的癌症诊断之外的普遍性问题。在一项基于人群的登记分析中,与DOACs相比,华法林与延长癌症相关性静脉血栓栓塞治疗的总生存期相关。
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引用次数: 0
Digital solutions to promote adolescent mental health: Opportunities and challenges for research and practice 促进青少年心理健康的数字解决方案:研究和实践的机遇和挑战
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1004008
J. Bantjes
Jason Bantjes discusses the accompanying study by Michelle Torok, Jin Han, and colleagues investigating the effects of a self-guided smartphone application on suicidal ideation among young adults.
Jason Bantjes讨论了Michelle Torok、Jin Han及其同事的相关研究,该研究调查了智能手机自助应用程序对年轻人自杀意念的影响。
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引用次数: 5
Call for Papers: PLOS Medicine Special Issue on the COVID-19 Pandemic and Global Mental Health 论文征集:《公共科学图书馆新冠肺炎疫情与全球心理健康医学特刊》
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1004010
Plos Medicine Editors
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引用次数: 1
Ukraine conflict: Prioritizing lives and health 乌克兰冲突:优先考虑生命和健康
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1004007
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引用次数: 4
Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness 更正:巴基斯坦信德省COVID-19疫苗接种:健康影响和成本效益建模研究
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1003990
Carl A. B. Pearson, F. Bozzani, S. Procter, N. Davies, M. Huda, H. T. Jensen, M. Keogh-Brown, Muhammad Khalid, S. Sweeney, S. Torres-Rueda, R. Eggo, A. Vassall, M. Jit
[This corrects the article DOI: 10.1371/journal.pmed.1003815.].
[此更正文章DOI: 10.1371/journal.pmed.1003815.]。
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引用次数: 1
Association of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional survey 越南芽庄婴儿肺炎球菌携带与接触者携带风险的相关性:一项嵌套横断面调查
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1004016
G. Qian, M. Toizumi, S. Clifford, L. Le, Tasos Papastylianou, C. Satzke, B. Quilty, C. Iwasaki, N. Kitamura, M. Takegata, M. Bui, H. Nguyen, D. Dang, A. V. van Hoek, L. Yoshida, S. Flasche
Background Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group. Hence, this study investigates pneumococcal transmission routes to infants in the coastal city of Nha Trang, Vietnam. Methods and findings In October 2018, we conducted a nested cross-sectional contact and pneumococcal carriage survey in randomly selected 4- to 11-month-old infants across all 27 communes of Nha Trang. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total, 1,583 infants between 4 and 13 months old participated, with 7,428 contacts reported. Few infants (5%, or 86 infants) attended day care, and carriage prevalence was 22% (353 infants). Most infants (61%, or 966 infants) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behaviour were highly correlated: If adjusted for age and locality, the odds of an infant’s carriage increased by 22% (95% confidence interval (CI): 15 to 29) per 10 percentage points increase in the probability to have had close contact with at least 1 pneumococcal carrier. Moreover, 2- to 6-year-old children contributed 51% (95% CI: 39 to 63) to the total direct pneumococcal exposure risks to infants in this setting. The main limitation of this study is that exposure risk was assessed indirectly by the age-dependent propensity for carriage of a contact and not by assessing carriage of such contacts directly. Conclusions In this study, we observed that cross-sectional contact and infection studies could help identify pneumococcal transmission routes and that preschool-age children may be the largest reservoir for pneumococcal transmission to infants in Nha Trang, Vietnam.
背景婴儿患肺炎球菌疾病的风险最高。它们通过群体效应提供的额外保护是考虑最佳肺炎球菌疫苗接种策略的关键部分。然而,目前对这一弱势年龄组的主要传播途径知之甚少。因此,本研究调查了越南芽庄沿海城市婴儿的肺炎球菌传播途径。方法和发现2018年10月,我们对芽庄所有27个社区随机选择的4至11个月大的婴儿进行了嵌套的横断面接触和肺炎球菌携带调查。贝叶斯逻辑回归模型用于估计人群中特定年龄段的携带流行率,这是一种特定年龄段接触可能导致婴儿接触肺炎球菌的概率的代理。我们使用另一个贝叶斯逻辑回归模型来估计婴儿携带与他们报告的至少一名接触者携带肺炎球菌的概率之间的相关性,控制年龄和地点。总共有1583名4至13个月大的婴儿参加,报告了7428名接触者。很少有婴儿(5%,即86名婴儿)参加日托,携带率为22%(353名婴儿)。大多数婴儿(61%,即966名婴儿)在调查当天与肺炎球菌携带者有过密切接触的概率不到25%。肺炎球菌感染风险和接触行为高度相关:如果根据年龄和地点进行调整,婴儿与至少1名肺炎球菌携带者密切接触的概率每增加10个百分点,携带婴儿的几率就会增加22%(95%置信区间:15-29)。此外,在这种情况下,2至6岁的儿童对婴儿直接接触肺炎球菌的总风险贡献了51%(95%CI:39至63)。这项研究的主要局限性是,暴露风险是通过携带接触者的年龄依赖性倾向间接评估的,而不是通过直接评估这种接触者的携带。结论在这项研究中,我们观察到横断面接触和感染研究有助于确定肺炎球菌的传播途径,学龄前儿童可能是越南芽庄婴儿肺炎球菌传播的最大宿主。
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引用次数: 3
Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial 5型腺病毒载体和蛋白质亚基新冠肺炎疫苗异源增强免疫的安全性和免疫原性(Convidecia/ZF2001):一项随机、观察者盲、安慰剂对照试验
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1003953
P. Jin, X. Guo, W. Chen, S. Ma, H. Pan, L. Dai, P. Du, L. Wang, L. Jin, Y. Chen, F. Shi, J. Liu, X. Xu, Y. Zhang, G. F. Gao, C. Chen, J. Feng, J. Li, Fujie Zhu
Background Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). Methods and findings We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study li
异种加强疫苗接种已被提出作为一种选择,以获得更强、更广泛或更持久的免疫。我们用重组腺病毒5型载体2019冠状病毒病(COVID-19)疫苗(Convidecia,以下简称CV)和基于蛋白亚单位的COVID-19疫苗(ZF2001,以下简称ZF)评估了异源免疫的安全性和免疫原性。方法和结果我们在中国江苏省进行了一项随机、观察者盲、安慰剂对照试验,招募年龄在18岁及以上、接受过1剂Convidecia、无严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染史的健康成年人。60名参与者随机分配(2:1),在启动后28天接受1剂ZF2001或安慰剂对照(三价灭活流感疫苗(TIV)),并在5个月时接受第三剂ZF2001注射,分别称为CV/ZF/ZF (D0-D28-M5)和CV/ZF (D0-M5)方案。60名参与者随机分配(2:1),在启动56天后接受1剂ZF2001或TIV,并在6个月时接受第三次注射ZF2001,分别称为CV/ZF/ZF (D0-D56-M6)和CV/ZF (D0-M6)方案。参与者和调查人员不知道所接种的疫苗,但不知道增强间隔。主要终点是针对野生型SARS-CoV-2的中和抗体的几何平均滴度(GMT)和7天征求的不良反应。初步分析是在意向治疗人群中进行的。在2021年4月7日至2021年5月6日期间,120名符合条件的参与者被随机分配到启动后28天5个月接受ZF2001/ZF2001 (n = 40)或TIV/ZF2001 (n = 20),并在启动后56天6个月接受ZF2001/ZF2001 (n = 40)或TIV/ZF2001 (n = 20)。其中7名受试者未接受ZF2001第三次注射。共有26名参与者(21.7%)报告了加强疫苗接种后7天内的不良反应,所有报告的不良反应均为轻度反应,其中CV/ZF/ZF (D0- d28 -M5)方案13人(32.5%),CV/ZF (D0- d56 - m6)方案7人(35.0%),CV/ZF/ZF (D0- d56 - m6)方案4人(10.0%),CV/ZF (D0- m6)方案2人(10.0%)。在第一次增强后14天,接种ZF2001后28天和56天的中和抗体GMTs分别为18.7 (95% CI 13.7至25.5)和25.9(17.0至39.3),与TIV相比,几何平均比率为2.0(1.2至3.5)和3.4(1.8至6.4)。第二次增强中和抗体后14天,CV/ZF/ZF (D0-D28-M5)方案的GMTs增加到107.2(73.7至155.8),CV/ZF/ZF (D0-D56-M6)方案的GMTs增加到141.2(83.4至238.8)。CV/ZF (D0-M5)和CV/ZF (D0-M6)两剂方案诱导的抗体水平与三剂方案相当,GMTs分别为90.5(45.6,179.8)和94.1(44.0,200.9)。研究的局限性包括在现实环境中缺乏疫苗有效性和目前缺乏免疫持久性数据。结论:初次接种牛头蚴后异源增强ZF2001比单次接种牛头蚴具有更强的免疫原性,且不存在安全性问题。这些结果支持了病毒载体和重组蛋白疫苗合作的灵活性。重组COVID-19疫苗(Ad5载体)与rbd蛋白亚单位疫苗异种补强试验注册研究ClinicalTrial.gov NCT04833101。
{"title":"Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial","authors":"P. Jin, X. Guo, W. Chen, S. Ma, H. Pan, L. Dai, P. Du, L. Wang, L. Jin, Y. Chen, F. Shi, J. Liu, X. Xu, Y. Zhang, G. F. Gao, C. Chen, J. Feng, J. Li, Fujie Zhu","doi":"10.1371/journal.pmed.1003953","DOIUrl":"https://doi.org/10.1371/journal.pmed.1003953","url":null,"abstract":"Background Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). Methods and findings We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study li","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47583749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
The effect of a therapeutic smartphone application on suicidal ideation in young adults: Findings from a randomized controlled trial in Australia 治疗性智能手机应用程序对年轻人自杀意念的影响:来自澳大利亚一项随机对照试验的结果
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-05-01 DOI: 10.1371/journal.pmed.1003978
M. Torok, Jin Han, L. McGillivray, Quincy J. J. Wong, A. Werner-Seidler, B. O’Dea, A. Calear, H. Christensen
Background Suicidal ideation is a major risk for a suicide attempt in younger people, such that reducing severity of ideation is an important target for suicide prevention. Smartphone applications present a new opportunity for managing ideation in young adults; however, confirmatory evidence for efficacy from randomized trials is lacking. The objective of this study was to assess whether a therapeutic smartphone application (“LifeBuoy”) was superior to an attention-matched control application at reducing the severity of suicidal ideation. Methods and findings In this 2-arm parallel, double-blind, randomized controlled trial, 455 young adults from Australia experiencing recent suicidal ideation and aged 18 to 25 years were randomly assigned in a 2:2 ratio to use a smartphone application for 6 weeks in May 2020, with the final follow-up in October 2020. The primary outcome was change in suicidal ideation symptom severity scores from baseline (T0) to postintervention (T1) and 3-month postintervention follow-up (T2), measured using the Suicidal Ideation Attributes Scale (SIDAS). Secondary outcomes were symptom changes in depression (Patient Health Questionnaire-9, PHQ-9), generalized anxiety (Generalized Anxiety Disorder-7, GAD-7), distress (Distress Questionnaire-5, DQ5), and well-being (Short Warwick–Edinburgh Mental Well-Being Scale, SWEMWBS). This trial was conducted online, using a targeted social media recruitment strategy. The intervention groups were provided with a self-guided smartphone application based on dialectical behavior therapy (DBT; “LifeBuoy”) to improve emotion regulation and distress tolerance. The control group were provided a smartphone application that looked like LifeBuoy (“LifeBuoy-C”), but delivered general (nontherapeutic) information on a range of health and lifestyle topics. Among 228 participants randomized to LifeBuoy, 110 did not complete the final survey; among 227 participants randomized to the control condition, 91 did not complete the final survey. All randomized participants were included in the intent-to-treat analysis for the primary and secondary outcomes. There was a significant time × condition effect for suicidal ideation scores in favor of LifeBuoy at T1 (p < 0.001, d = 0.45) and T2 (p = 0.007, d = 0.34). There were no superior intervention effects for LifeBuoy on any secondary mental health outcomes from baseline to T1 or T2 [p-values: 0.069 to 0.896]. No serious adverse events (suicide attempts requiring medical care) were reported. The main limitations of the study are the lack of sample size calculations supporting the study to be powered to detect changes in secondary outcomes and a high attrition rate at T2, which may lead efficacy to be overestimated. Conclusions LifeBuoy was associated with superior improvements in suicidal ideation severity, but not secondary mental health outcomes, compared to the control application, LifeBuoy-C. Digital therapeutics may need to be purposefully designed to targe
背景自杀意念是年轻人自杀未遂的主要风险,因此降低意念的严重程度是预防自杀的重要目标。智能手机应用程序为管理年轻人的意念提供了新的机会;然而,缺乏来自随机试验的有效性的证实性证据。本研究的目的是评估治疗性智能手机应用程序(“LifeBuoy”)在降低自杀意念严重程度方面是否优于注意力匹配的对照应用程序。方法和发现在这项两组平行、双盲、随机对照试验中,455名来自澳大利亚的18至25岁的年轻人在2020年5月以2:2的比例被随机分配使用智能手机应用程序6周,最终随访时间为2020年10月。主要结果是自杀意念症状严重程度评分从基线(T0)到干预后(T1)和干预后3个月随访(T2)的变化,使用自杀意念属性量表(SIDAS)进行测量。次要结果是抑郁(患者健康问卷-9,PHQ-9)、广泛性焦虑(广泛性焦虑障碍-7,GAD-7)、痛苦(痛苦问卷-5,DQ5)和幸福感(Short Warwick–Edinburgh心理健康量表,SWEWBS)的症状变化。这项试验是在网上进行的,采用了有针对性的社交媒体招聘策略。为干预组提供了一款基于辩证行为疗法(DBT;“LifeBuoy”)的自助智能手机应用程序,以改善情绪调节和痛苦耐受能力。对照组获得了一个看起来像LifeBuoy(“LifeBuoy-C”)的智能手机应用程序,但提供了一系列健康和生活方式主题的一般(非治疗)信息。在随机分配到LifeBuoy的228名参与者中,110人没有完成最终调查;227名被随机分配到对照组的参与者中,有91人没有完成最终调查。所有随机参与者都被纳入了主要和次要结果的意向治疗分析。在T1(p<0.001,d=0.45)和T2(p=0.007,d=0.34)时,LifeBuoy对自杀意念得分有显著的时间×条件效应。从基线到T1或T2,LifeBuoy[p值:0.069至0.896]对任何次要心理健康结果都没有优越的干预效果。没有严重不良事件(需要医疗护理的自杀企图)的报告。该研究的主要局限性是缺乏支持该研究检测次要结果变化的样本量计算,以及T2时的高流失率,这可能导致疗效被高估。结论与对照应用LifeBuoy-C相比,LifeBuoy与自杀意念严重程度的改善有关,但与次要心理健康结果无关。数字疗法可能需要有目的地设计,以针对特定的健康结果,从而具有疗效。试验注册澳大利亚-新西兰临床试验注册ACTRN12619001671156
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引用次数: 16
Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data. 南亚的食物环境与糖尿病:健康结果数据的地理空间分析
IF 15.8 1区 医学 Q1 Medicine Pub Date : 2022-04-26 eCollection Date: 2022-04-01 DOI: 10.1371/journal.pmed.1003970
Dian Kusuma, Petya Atanasova, Elisa Pineda, Ranjit Mohan Anjana, Laksara De Silva, Abu Am Hanif, Mehedi Hasan, Md Mokbul Hossain, Susantha Indrawansa, Deepal Jayamanne, Sujeet Jha, Anuradhani Kasturiratne, Prasad Katulanda, Khadija I Khawaja, Balachandran Kumarendran, Malay K Mridha, Vindya Rajakaruna, John C Chambers, Gary Frost, Franco Sassi, Marisa Miraldo

Background: The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people's diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.

Methods and findings: We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant's home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual's home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study's key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.

Conclusions: Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

背景2型糖尿病(T2DM)的全球流行使其预防成为公共卫生的主要优先事项。糖尿病的一个关键风险因素是肥胖和不良饮食。食物环境已被发现会影响人们的饮食和肥胖,这表明它们可能在糖尿病的流行中发挥作用。然而,很少有证据表明它们在中低收入国家中可能发挥的作用。我们研究了成人中食物环境与T2DM的关系及其收入和性别的异质性。方法和发现我们根据2018年至2020年在孟加拉国和斯里兰卡收集的环境测绘调查数据,将来自健康监测点网络(南亚生物库)的12167人的个人健康结果数据与他们家周围食品店的密度和邻近度联系起来。密度被定义为距离研究参与者家300米范围内的食物出口份额,接近度被定义为离家100米范围内至少有一个出口。结果变量包括空腹血糖水平、高血糖和自我报告诊断的糖尿病。控制变量包括人口统计、社会经济地位(SES)、健康状况、医疗保健利用率和体育活动。数据在ArcMap 10.3和STATA 15.1中进行分析。较高比例的快餐店(FFR)与9.21 mg/dl的血糖升高有关(95%可信区间:0.17,18.24;p<0.05)。附近至少有1个FFR与2.14 mg/dl的葡萄糖升高有关(可信区间:0.55,3.72;p<0.01)。个人家附近的FFR增加1%与被临床诊断的概率增加8%有关作为糖尿病患者(平均边际效应(AMEs):0.08;CI:0.02.0.14;在家附近至少有1个FFR与血糖水平升高和诊断为糖尿病的几率分别增加16%(比值比[OR]:1.16;CI:1.01,1.33;p<0.05)和19%(比值比:1.19;CI:1.03,1.38;p<0.05)相关。女性的FFR密度与血糖水平之间的正相关性比男性更强,但男性和高收入人群的FFR接近度与血糖水平的相关性更强。该研究的一个关键局限性是,我们测量了居住地理位置周围的食物环境暴露量;然而,参与者可能会从其他地方获得食物。结论我们的研究结果表明,接触快餐店可能会对2型糖尿病的风险产生不利影响,尤其是在女性和高收入人群中。政策应针对食品环境的变化,促进更好的饮食和预防2型糖尿病。
{"title":"Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data.","authors":"Dian Kusuma,&nbsp;Petya Atanasova,&nbsp;Elisa Pineda,&nbsp;Ranjit Mohan Anjana,&nbsp;Laksara De Silva,&nbsp;Abu Am Hanif,&nbsp;Mehedi Hasan,&nbsp;Md Mokbul Hossain,&nbsp;Susantha Indrawansa,&nbsp;Deepal Jayamanne,&nbsp;Sujeet Jha,&nbsp;Anuradhani Kasturiratne,&nbsp;Prasad Katulanda,&nbsp;Khadija I Khawaja,&nbsp;Balachandran Kumarendran,&nbsp;Malay K Mridha,&nbsp;Vindya Rajakaruna,&nbsp;John C Chambers,&nbsp;Gary Frost,&nbsp;Franco Sassi,&nbsp;Marisa Miraldo","doi":"10.1371/journal.pmed.1003970","DOIUrl":"10.1371/journal.pmed.1003970","url":null,"abstract":"<p><strong>Background: </strong>The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people's diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.</p><p><strong>Methods and findings: </strong>We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant's home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual's home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study's key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.</p><p><strong>Conclusions: </strong>Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.</p>","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49273648","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: 7
Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial. 瑞芬太尼全麻过程中基于大脑的伤害感受测量:一项随机对照试验
IF 10.5 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2022-04-22 eCollection Date: 2022-04-01 DOI: 10.1371/journal.pmed.1003965
Keerthana Deepti Karunakaran, Barry D Kussman, Ke Peng, Lino Becerra, Robert Labadie, Rachel Bernier, Delany Berry, Stephen Green, David Zurakowski, Mark E Alexander, David Borsook

Background: Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.

Methods and findings: We investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children's Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = -1.138, 95% CI = -2.062, -0.214, p = 0.002) and superior mFPC (MD = -0.999, 95% CI = -1.961, -0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and highe

背景:导管射频消融治疗心律失常是一个痛苦的过程。先前使用功能性近红外光谱(fNIRS)对全身麻醉患者进行的研究表明,消融导致疼痛相关皮质区域的活动,可能是由于心脏系统内传入伤害感受器的阻断不足。有一个客观的基于大脑的疼痛和镇痛测量可能在未来允许在外科手术过程中加强镇痛控制。因此,本研究的主要目的是证明外科手术中广泛使用的阿片类药物瑞芬太尼可以减弱fNIRS皮质对心脏消融的反应。方法和结果研究了麻醉下心脏消融过程中连续使用瑞芬太尼对皮质血流动力学的影响。在一项随机、双盲、安慰剂(PL)对照试验中,我们研究了2016年10月至2020年3月在波士顿儿童医院心内科接受导管消融治疗心律失常的32例儿科患者(平均年龄15.8岁,16例女性);0.9% NaCl组9例,低剂量(LD)瑞芬太尼组12例(0.25 mcg/kg/min),高剂量(HD)瑞芬太尼组11例(0.5 mcg/kg/min)。术中应用连续波近红外成像系统记录初级体感皮层和前额叶皮层的血流动力学变化。主要观察指标是PL组与瑞芬太尼组在消融后内侧额极皮质(mFPC)、外侧前额皮质(lPFC)和初级体感皮质(S1)的血红蛋白浓度(NadirHbO,即最低血红蛋白浓度)和PeakHbO(即峰值变化和曲线下面积)的变化。次要测量包括fNIRS对听觉控制条件的反应。在意向治疗(ITT)的基础上进行数据分析。将瑞芬太尼组(联合剂量亚组)与PL进行比较,并进行事后分析以确定剂量效应。没有不良事件发生。两组在年龄、性别和消融次数上具有可比性。结果显示,雷芬太尼与PL组相比,PL组在低度mFPC(平均差值(MD) = 1.229, 95%可信区间[CI] = 0.334, 2.124, p < 0.001)和优度mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001)中表现出更高的NadirHbO,在低度mFPC (MD = - 1.138, 95% CI = - 2.062, - 0.214, p = 0.002)和优度mFPC (MD = - 0.999, 95% CI = - 1.961, - 0.036, p = 0.008)中表现出更高的PeakHbO。消融引起的S1激活在PL组中最大,其次是LD组和HD组,但未达到显著性,而消融引起的lPFC激活在所有组中相似。消融与听觉刺激相比,下位mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004)和上位mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001)的PeakHbO较高,后位上位S1 (Pos. SS1;MD =−0.342,95% CI =−0.680,−0.004,p = 0.007)。雷米芬太尼组在两种刺激下,较差mFPC的NadirHbO (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003)和较优mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003)和较优mFPC的PeakHbO (MD = - 0.092, 95% CI = - 0.680, - 0.004, p = 0.007)均较小。研究的局限性是样本量小,手术后的运动,间接测量伤害感受,近红外光谱穿透深度浅,只能进入皮层浅层。结论:我们观察到瑞芬太尼全身麻醉下心脏消融过程中与伤害感受相关的皮质活动。它强调了fNIRS在无意识患者中提供客观疼痛测量的潜力,其中基于皮层的测量可能比目前的评估方法更准确。未来的研究可能会扩展这一应用,以产生疼痛的实时指示,这将有助于临床医生提供即时和充分的疼痛治疗。临床试验注册:ClinicalTrials.gov NCT02703090
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引用次数: 0
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