Pub Date : 2022-06-01DOI: 10.1371/journal.pmed.1004023
O. Plana-Ripoll, J. Dreier, N. Momen, Anders Prior, N. Weye, P. Mortensen, C. Pedersen, K. Iburg, M. Christensen, T. Laursen, E. Agerbo, M. Pedersen, J. Brandt, L. Frohn, C. Geels, J. Christensen, J. Mcgrath
Background The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. Methods and findings In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. Conclusions In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.
{"title":"Analysis of mortality metrics associated with a comprehensive range of disorders in Denmark, 2000 to 2018: A population-based cohort study","authors":"O. Plana-Ripoll, J. Dreier, N. Momen, Anders Prior, N. Weye, P. Mortensen, C. Pedersen, K. Iburg, M. Christensen, T. Laursen, E. Agerbo, M. Pedersen, J. Brandt, L. Frohn, C. Geels, J. Christensen, J. Mcgrath","doi":"10.1371/journal.pmed.1004023","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004023","url":null,"abstract":"Background The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. Methods and findings In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. Conclusions In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49594433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-31eCollection Date: 2022-05-01DOI: 10.1371/journal.pmed.1003999
Cédric Annweiler, Mélinda Beaudenon, Jennifer Gautier, Justine Gonsard, Sophie Boucher, Guillaume Chapelet, Astrid Darsonval, Bertrand Fougère, Olivier Guérin, Marjorie Houvet, Pierre Ménager, Claire Roubaud-Baudron, Achille Tchalla, Jean-Claude Souberbielle, Jérémie Riou, Elsa Parot-Schinkel, Thomas Célarier
<p><strong>Background: </strong>Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).</p><p><strong>Methods and findings: </strong>This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of
背景根据实验数据和小型非受控观察性研究的数据，已提出补充维生素D作为2019冠状病毒病（新冠肺炎）的治疗方法。COvid19和维生素d试验（COVIT-TRIAL）研究旨在测试在诊断为新冠肺炎后72小时内单次口服高剂量胆钙化醇（维生素D3）与标准域胆钙化醇相比，是否能改善感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的高危老年人的14天总生存率。方法和结果这项多中心、随机、对照、开放标签、优越性试验涉及法国9个医疗中心的合作。入住医院或居住在研究中心附近养老院的患者，如果年龄≥65岁，严重急性呼吸系统综合征冠状病毒2型感染少于3天，且至少有1个新冠肺炎恶化危险因素（年龄≥75岁，SpO2≤94%，或PaO2/FiO2≤300 mm Hg），则符合条件。主要的非纳入标准是需要ICU的器官衰竭，尽管有5L/min的氧气，SpO2≤92%，前一个月的预期寿命为800IU/天，以及维生素D补充剂的禁忌症。符合条件且同意的患者在诊断为新冠肺炎后72小时内，在医疗监督下随机分配单次口服高剂量（400000国际单位）或标准域（50000国际单位）胆钙化醇。参与者和当地研究人员在分配的治疗中没有戴口罩，但指导委员会和数据与安全监测委员会在试验期间对随机化组和结果数据戴口罩。主要结果是14天的总死亡率。在2020年4月15日至12月17日期间，在1207名接受COVIT-TRIAL研究资格评估的患者中，254名符合资格标准并形成意向治疗人群。中位年龄为88岁（IQR，82至92），148名患者（58%）为女性。127例患者中有8例（6%）接受高剂量胆钙化醇治疗，127名接受标准剂量胆钙化醇治疗的患者中，有14名（11%）在14天内死亡（调整后的危险比=0.39[95%置信区间[CI]，0.16至0.99]，P=0.049，在控制了随机分层[即年龄、氧气需求、住院治疗、抗生素、抗感染药物和/或皮质类固醇的使用]和重要预后因素的基线失衡后）[即，性别、正在进行的癌症、大量腹泻和基线时的谵妄]）。一人受益（NNTB）需要治疗的人数为21人[NNTB 9至∞对一人伤害（NNTH）需要治疗人数46]。新冠肺炎导致的14天死亡率也有明显的益处（高剂量组7例（6%）死亡，标准剂量组14例（11%）死亡；调整后的危险比=0.33[95%CI，0.12至0.86]，P=0.02）。单次口服高剂量给药的保护作用在28天时没有持续（高剂量组死亡19例（15%），标准剂量组死亡21例（17%）；调整后的危险比=0.70[95%CI，0.36-1.36]，P=0.29）。与标准剂量相比，高剂量胆钙化醇不会导致更频繁的不良反应。开放标签设计和有限的学习能力是本研究的主要局限性。结论在这项随机对照试验（RCT）中，我们观察到，对有风险的新冠肺炎老年患者早期给予高剂量与标准域维生素D3可改善第14天的总体死亡率。28天后不再观察到这种效果。试验注册ClinicalTrials.gov NCT04344041。
{"title":"High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.","authors":"Cédric Annweiler, Mélinda Beaudenon, Jennifer Gautier, Justine Gonsard, Sophie Boucher, Guillaume Chapelet, Astrid Darsonval, Bertrand Fougère, Olivier Guérin, Marjorie Houvet, Pierre Ménager, Claire Roubaud-Baudron, Achille Tchalla, Jean-Claude Souberbielle, Jérémie Riou, Elsa Parot-Schinkel, Thomas Célarier","doi":"10.1371/journal.pmed.1003999","DOIUrl":"10.1371/journal.pmed.1003999","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).</p><p><strong>Methods and findings: </strong>This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":"e1003999"},"PeriodicalIF":9.9,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48720445","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 : 2022-05-17DOI: 10.1101/2022.05.16.22275122
Shulin Chen, Y. Conwell, Jiang Xue, Lydia W. Li, Tingjie Zhao, W. Tang, Hillary Bogner, Hengjin Dong
Background : Effectiveness of integrated care management for common, comorbid physical and mental disorders has been insufficiently examined in low- and middle-income countries. We tested hypotheses that older adults treated in rural Chinese primary care clinics with integrated care management of comorbid depression and HTN would show greater improvements in depression symptom severity and hypertension (HTN) control than those who received usual care. Methods and findings : The study was a 12-month cluster randomized controlled trial conducted from 2014 through 2017, with analyses conducted in 2020-2021. Subjects were rural village clinics of randomly selected towns in Zhejiang Province, China. Ten towns with a total of 218 rural village primary care clinics were randomized, five towns each, to deliver the Chinese Older Adult Collaborations in Health (COACH) intervention or enhanced care-as-usual (eCAU). The COACH intervention consisted of algorithm-driven treatment of depression and HTN by village primary care doctors supported by village lay workers with consultation from centrally-located psychiatrists. Subjects included clinic patients aged >=60 years with a diagnosis of HTN and clinically significant depressive symptoms (PHQ-9 score >=10). Of 2899 eligible subjects, 2365 (82%) agreed to participate and were followed for 12 months. Observers were blinded to study hypotheses but not to group assignment. Primary outcomes specified a priori were change in depression symptom severity and proportion with controlled HTN. Compared with 1133 subjects who received eCAU, 1232 COACH subjects showed greater reduction in depressive symptoms (Cohens d [{+/-}SD] = -0.21 [-0.25, -0.17]) and greater likelihood of achieving HTN control (OR [95% CI] = 18.24 [8.40, 39.63]). Exploratory post hoc analyses showed that COACH subjects who accepted an antidepressant had greater symptom reduction than either those who declined the medication or received eCAU. HTN control improved in COACH subjects regardless of antidepressant use. Conclusions : The COACH model appears effective in managing comorbid depression and HTN in older adult residents of rural Chinese villages. Integrated care management of comorbid depression and common medical illness may be a useful approach in other low resourced settings in which specialty geriatric mental health care is lacking.
{"title":"Effectiveness of integrated care for older adults with depression and hypertension in rural China: A cluster randomized controlled trial","authors":"Shulin Chen, Y. Conwell, Jiang Xue, Lydia W. Li, Tingjie Zhao, W. Tang, Hillary Bogner, Hengjin Dong","doi":"10.1101/2022.05.16.22275122","DOIUrl":"https://doi.org/10.1101/2022.05.16.22275122","url":null,"abstract":"Background : Effectiveness of integrated care management for common, comorbid physical and mental disorders has been insufficiently examined in low- and middle-income countries. We tested hypotheses that older adults treated in rural Chinese primary care clinics with integrated care management of comorbid depression and HTN would show greater improvements in depression symptom severity and hypertension (HTN) control than those who received usual care. Methods and findings : The study was a 12-month cluster randomized controlled trial conducted from 2014 through 2017, with analyses conducted in 2020-2021. Subjects were rural village clinics of randomly selected towns in Zhejiang Province, China. Ten towns with a total of 218 rural village primary care clinics were randomized, five towns each, to deliver the Chinese Older Adult Collaborations in Health (COACH) intervention or enhanced care-as-usual (eCAU). The COACH intervention consisted of algorithm-driven treatment of depression and HTN by village primary care doctors supported by village lay workers with consultation from centrally-located psychiatrists. Subjects included clinic patients aged >=60 years with a diagnosis of HTN and clinically significant depressive symptoms (PHQ-9 score >=10). Of 2899 eligible subjects, 2365 (82%) agreed to participate and were followed for 12 months. Observers were blinded to study hypotheses but not to group assignment. Primary outcomes specified a priori were change in depression symptom severity and proportion with controlled HTN. Compared with 1133 subjects who received eCAU, 1232 COACH subjects showed greater reduction in depressive symptoms (Cohens d [{+/-}SD] = -0.21 [-0.25, -0.17]) and greater likelihood of achieving HTN control (OR [95% CI] = 18.24 [8.40, 39.63]). Exploratory post hoc analyses showed that COACH subjects who accepted an antidepressant had greater symptom reduction than either those who declined the medication or received eCAU. HTN control improved in COACH subjects regardless of antidepressant use. Conclusions : The COACH model appears effective in managing comorbid depression and HTN in older adult residents of rural Chinese villages. Integrated care management of comorbid depression and common medical illness may be a useful approach in other low resourced settings in which specialty geriatric mental health care is lacking.","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44908445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1004014
The editors of PLOS Medicine, together with guest editors Timothy Walsh, Ramanan Laxminarayan and Ana Cristina Gales, announce a forthcoming Special Issue dedicated to bacterial antimicrobial resistance (AMR). Research submissions are now being invited. The emergence of pathogenic bacteria which cannot be effectively treated with existing drugs has been prioritised by the World Health Organization as one of the top ten global public health threats facing humanity [1]. Drug-resistant infections are associated with substantial morbidity and mortality, and were estimated to contribute to 4.95 million deaths globally in 2019 [2]. The burden of antimicrobial resistance (AMR) is disproportionately observed in lowand middleincome countries (LMICs), particularly sub-Saharan Africa [2]. Without intervention, it has been estimated that global deaths attributable to AMR could reach 10 million annually by 2050 [3]. AMR is a One Health problem and its causes lie in human, animal and environmental domains. The overuse and misuse of antibiotics, and the potential for transmission within and between these domains is responsible for the rapid global spread of drug-resistant pathogens. Use of antibiotics increased by 65% globally between 2000 and 2015, and more than doubled in LMICs over the same period [4]. Pathogen AMR evolution can limit the effectiveness of available antibiotics and far outpaces our ability to develop new drugs. Of the 32 antibiotics in clinical development to tackle priority pathogens in 2019, only six were classified as innovative [5]. Action to impede the development of drug-resistance is urgently required. The guest editors and PLOS Medicine editors seek high-quality and high-impact research submissions related to the main drivers, surveillance and prevention of bacterial antimicrobial resistance, particularly in lowand middle-income settings. Areas of particular interest include the prevalence and clinical challenges of drug-resistant bacteria, interventions to reduce disease transmission, diagnostics informing antimicrobial prescribing, misuse and overuse of antimicrobials, economics of antimicrobial access and use, and One Health interventions to reduce AMR. Submission of articles related to pathogens of highest concern and highest global burden (excluding Mycobacterium tuberculosis) are strongly encouraged. Please see plos.io/AMR for more detailed information. To submit your manuscript for consideration, please visit http://journals.plos.org/ plosmedicine/s/submit-now, indicating your interest in the Special Issue in your cover letter. Questions about the Special Issue can be directed to plosmedicine@plos.org. The submission deadline is July 15 2022.
{"title":"Call for Papers: PLOS Medicine Special Issue on Bacterial Antimicrobial Resistance—Surveillance and Prevention","authors":"","doi":"10.1371/journal.pmed.1004014","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004014","url":null,"abstract":"The editors of PLOS Medicine, together with guest editors Timothy Walsh, Ramanan Laxminarayan and Ana Cristina Gales, announce a forthcoming Special Issue dedicated to bacterial antimicrobial resistance (AMR). Research submissions are now being invited. The emergence of pathogenic bacteria which cannot be effectively treated with existing drugs has been prioritised by the World Health Organization as one of the top ten global public health threats facing humanity [1]. Drug-resistant infections are associated with substantial morbidity and mortality, and were estimated to contribute to 4.95 million deaths globally in 2019 [2]. The burden of antimicrobial resistance (AMR) is disproportionately observed in lowand middleincome countries (LMICs), particularly sub-Saharan Africa [2]. Without intervention, it has been estimated that global deaths attributable to AMR could reach 10 million annually by 2050 [3]. AMR is a One Health problem and its causes lie in human, animal and environmental domains. The overuse and misuse of antibiotics, and the potential for transmission within and between these domains is responsible for the rapid global spread of drug-resistant pathogens. Use of antibiotics increased by 65% globally between 2000 and 2015, and more than doubled in LMICs over the same period [4]. Pathogen AMR evolution can limit the effectiveness of available antibiotics and far outpaces our ability to develop new drugs. Of the 32 antibiotics in clinical development to tackle priority pathogens in 2019, only six were classified as innovative [5]. Action to impede the development of drug-resistance is urgently required. The guest editors and PLOS Medicine editors seek high-quality and high-impact research submissions related to the main drivers, surveillance and prevention of bacterial antimicrobial resistance, particularly in lowand middle-income settings. Areas of particular interest include the prevalence and clinical challenges of drug-resistant bacteria, interventions to reduce disease transmission, diagnostics informing antimicrobial prescribing, misuse and overuse of antimicrobials, economics of antimicrobial access and use, and One Health interventions to reduce AMR. Submission of articles related to pathogens of highest concern and highest global burden (excluding Mycobacterium tuberculosis) are strongly encouraged. Please see plos.io/AMR for more detailed information. To submit your manuscript for consideration, please visit http://journals.plos.org/ plosmedicine/s/submit-now, indicating your interest in the Special Issue in your cover letter. Questions about the Special Issue can be directed to plosmedicine@plos.org. The submission deadline is July 15 2022.","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42191673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1004002
Brenda de Kok, L. Toe, Giles T. Hanley-Cook, Alemayehu Argaw, M. Ouédraogo, Anderson Compaoré, Katrien Vanslambrouck, Trenton Dailey-Chwalibóg, R. Ganaba, P. Kolsteren, L. Huybregts, C. Lachat
Background Providing balanced energy–protein (BEP) supplements is a promising intervention to improve birth outcomes in low- and middle-income countries (LMICs); however, evidence is limited. We aimed to assess the efficacy of fortified BEP supplementation during pregnancy to improve birth outcomes, as compared to iron–folic acid (IFA) tablets, the standard of care. Methods and findings We conducted an individually randomized controlled efficacy trial (MIcronutriments pour la SAnté de la Mère et de l’Enfant [MISAME]-III) in 6 health center catchment areas in rural Burkina Faso. Pregnant women, aged 15 to 40 years with gestational age (GA) <21 completed weeks, were randomly assigned to receive either fortified BEP supplements and IFA (intervention) or IFA (control). Supplements were provided during home visits, and intake was supervised on a daily basis by trained village-based project workers. The primary outcome was prevalence of small-for-gestational age (SGA) and secondary outcomes included large-for-gestational age (LGA), low birth weight (LBW), preterm birth (PTB), gestational duration, birth weight, birth length, Rohrer’s ponderal index, head circumference, thoracic circumference, arm circumference, fetal loss, and stillbirth. Statistical analyses followed the intention-to-treat (ITT) principle. From October 2019 to December 2020, 1,897 pregnant women were randomized (960 control and 937 intervention). The last child was born in August 2021, and birth anthropometry was analyzed from 1,708 pregnancies (872 control and 836 intervention). A total of 22 women were lost to follow-up in the control group and 27 women in the intervention group. BEP supplementation led to a mean 3.1 percentage points (pp) reduction in SGA with a 95% confidence interval (CI) of −7.39 to 1.16 (P = 0.151), indicating a wide range of plausible true treatment efficacy. Adjusting for prognostic factors of SGA, and conducting complete cases (1,659/1,708, 97%) and per-protocol analysis among women with an observed BEP adherence ≥75% (1,481/1,708, 87%), did not change the results. The intervention significantly improved the duration of gestation (+0.20 weeks, 95% CI 0.05 to 0.36, P = 0.010), birth weight (50.1 g, 8.11 to 92.0, P = 0.019), birth length (0.20 cm, 0.01 to 0.40, P = 0.044), thoracic circumference (0.20 cm, 0.04 to 0.37, P = 0.016), arm circumference (0.86 mm, 0.11 to 1.62, P = 0.025), and decreased LBW prevalence (−3.95 pp, −6.83 to −1.06, P = 0.007) as secondary outcomes measures. No differences in serious adverse events [SAEs; fetal loss (21 control and 26 intervention) and stillbirth (16 control and 17 intervention)] between the study groups were found. Key limitations are the nonblinded administration of supplements and the lack of information on other prognostic factors (e.g., infection, inflammation, stress, and physical activity) to determine to which extent these might have influenced the effect on nutrient availability and birth outcomes. Conclusions T
提供平衡的能量蛋白(BEP)补充剂是改善中低收入国家(LMICs)出生结局的一种有希望的干预措施;然而，证据有限。我们的目的是评估妊娠期间强化叶酸补充剂与铁叶酸(IFA)片(护理标准)相比改善分娩结局的功效。我们在布基纳法索农村的6个保健中心集水区进行了一项单独随机对照疗效试验(微量营养素为儿童提供微量营养素[MISAME]-III)。年龄在15 ~ 40岁、胎龄<21完整周的孕妇被随机分配接受强化BEP补充剂和IFA(干预)或IFA(对照组)。在家访期间提供补充，并由训练有素的乡村项目工作人员每天监督摄入情况。主要结局是小胎龄(SGA)的发生率，次要结局包括大胎龄(LGA)、低出生体重(LBW)、早产(PTB)、妊娠期、出生体重、出生长度、Rohrer氏指数、头围、胸围、臂围、胎儿丢失和死胎。统计分析遵循意向治疗(ITT)原则。2019年10月至2020年12月，随机选取1897名孕妇(对照组960名，干预组937名)。最后一个孩子于2021年8月出生，并对1708例妊娠(对照组872例，干预组836例)进行出生人体测量分析。对照组共有22名妇女失去随访，干预组有27名妇女失去随访。BEP补充导致SGA平均降低3.1个百分点(pp)， 95%置信区间(CI)为- 7.39至1.16 (P = 0.151)，表明在很大范围内可行的真实治疗效果。调整SGA的预后因素，对观察到的BEP依从性≥75%的妇女进行完整病例(1,659/ 1,708,97%)和按方案分析(1,481/ 1,708,87%)，没有改变结果。干预显著改善了妊娠期(+0.20周，95% CI 0.05 ~ 0.36, P = 0.010)、出生体重(50.1 g, 8.11 ~ 92.0, P = 0.019)、出生长度(0.20 cm, 0.01 ~ 0.40, P = 0.044)、胸围(0.20 cm, 0.04 ~ 0.37, P = 0.016)、臂围(0.86 mm, 0.11 ~ 1.62, P = 0.025)，并降低了LBW患病率(- 3.95 pp， - 6.83 ~ - 1.06, P = 0.007)。严重不良事件无差异[sae];研究组之间有胎儿丢失(对照组21例，干预组26例)和死产(对照组16例，干预组17例)。主要的限制是补充剂的非盲给药和缺乏其他预后因素(如感染、炎症、压力和身体活动)的信息，以确定这些因素在多大程度上可能影响营养物质的可用性和出生结果。MISAME-III试验并没有提供证据证明强化BEP补充剂对降低SGA患病率是有效的。然而，干预对其他分娩结果有很小的积极影响。额外的母体和生化结果需要调查，以提供进一步的证据，证明补充BEP的整体临床相关性。临床试验注册:ClinicalTrials.gov NCT03533712。
{"title":"Prenatal fortified balanced energy-protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial","authors":"Brenda de Kok, L. Toe, Giles T. Hanley-Cook, Alemayehu Argaw, M. Ouédraogo, Anderson Compaoré, Katrien Vanslambrouck, Trenton Dailey-Chwalibóg, R. Ganaba, P. Kolsteren, L. Huybregts, C. Lachat","doi":"10.1371/journal.pmed.1004002","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004002","url":null,"abstract":"Background Providing balanced energy–protein (BEP) supplements is a promising intervention to improve birth outcomes in low- and middle-income countries (LMICs); however, evidence is limited. We aimed to assess the efficacy of fortified BEP supplementation during pregnancy to improve birth outcomes, as compared to iron–folic acid (IFA) tablets, the standard of care. Methods and findings We conducted an individually randomized controlled efficacy trial (MIcronutriments pour la SAnté de la Mère et de l’Enfant [MISAME]-III) in 6 health center catchment areas in rural Burkina Faso. Pregnant women, aged 15 to 40 years with gestational age (GA) <21 completed weeks, were randomly assigned to receive either fortified BEP supplements and IFA (intervention) or IFA (control). Supplements were provided during home visits, and intake was supervised on a daily basis by trained village-based project workers. The primary outcome was prevalence of small-for-gestational age (SGA) and secondary outcomes included large-for-gestational age (LGA), low birth weight (LBW), preterm birth (PTB), gestational duration, birth weight, birth length, Rohrer’s ponderal index, head circumference, thoracic circumference, arm circumference, fetal loss, and stillbirth. Statistical analyses followed the intention-to-treat (ITT) principle. From October 2019 to December 2020, 1,897 pregnant women were randomized (960 control and 937 intervention). The last child was born in August 2021, and birth anthropometry was analyzed from 1,708 pregnancies (872 control and 836 intervention). A total of 22 women were lost to follow-up in the control group and 27 women in the intervention group. BEP supplementation led to a mean 3.1 percentage points (pp) reduction in SGA with a 95% confidence interval (CI) of −7.39 to 1.16 (P = 0.151), indicating a wide range of plausible true treatment efficacy. Adjusting for prognostic factors of SGA, and conducting complete cases (1,659/1,708, 97%) and per-protocol analysis among women with an observed BEP adherence ≥75% (1,481/1,708, 87%), did not change the results. The intervention significantly improved the duration of gestation (+0.20 weeks, 95% CI 0.05 to 0.36, P = 0.010), birth weight (50.1 g, 8.11 to 92.0, P = 0.019), birth length (0.20 cm, 0.01 to 0.40, P = 0.044), thoracic circumference (0.20 cm, 0.04 to 0.37, P = 0.016), arm circumference (0.86 mm, 0.11 to 1.62, P = 0.025), and decreased LBW prevalence (−3.95 pp, −6.83 to −1.06, P = 0.007) as secondary outcomes measures. No differences in serious adverse events [SAEs; fetal loss (21 control and 26 intervention) and stillbirth (16 control and 17 intervention)] between the study groups were found. Key limitations are the nonblinded administration of supplements and the lack of information on other prognostic factors (e.g., infection, inflammation, stress, and physical activity) to determine to which extent these might have influenced the effect on nutrient availability and birth outcomes. Conclusions T","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47780778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1003984
C. Sudfeld, L. Bliznashka, Aichatou Salifou, O. Guindo, Issaka Soumana, Irène Adehossi, C. Langendorf, R. Grais, Sheila Isanaka
Background It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials. Methods and findings We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages. Conclusions There was no benefit of prenatal MMS on child deve
{"title":"Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial","authors":"C. Sudfeld, L. Bliznashka, Aichatou Salifou, O. Guindo, Issaka Soumana, Irène Adehossi, C. Langendorf, R. Grais, Sheila Isanaka","doi":"10.1371/journal.pmed.1003984","DOIUrl":"https://doi.org/10.1371/journal.pmed.1003984","url":null,"abstract":"Background It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials. Methods and findings We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages. Conclusions There was no benefit of prenatal MMS on child deve","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47182100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1003997
J. Holm, G. Ferrari, A. Holmgren, F. Vánky, Ö. Friberg, M. Vidlund, R. Svedjeholm
Background Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG. Methods and findings A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation. Conclusions Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation. Trial registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824. European Union Drug Regulating Authorities Clinical Trials Database (Eudra CT number 2011-006241-15).
背景动物和人体资料表明，谷氨酸能促进缺血后心肌代谢和功能的恢复。N-末端脑钠肽原（NT-proBNP）反映冠状动脉搭桥术（CABG）后的心肌功能障碍。我们研究了谷氨酸盐输注是否能降低冠状动脉旁路移植术后中高危患者NT-proBNP的升高。方法和发现一项前瞻性、随机、双盲研究纳入了2015年11月15日至2020年9月30日的患者，在瑞典的4个学术心脏外科中心进行了为期30天的随访。患者接受CABG±瓣膜手术，左心室射血分数≤0.30或EuroSCORE II≥3.0。在释放主动脉交叉夹之前10至20分钟开始以1.65 mL/kg/h的速度静脉输注0.125 M L-谷氨酸或生理盐水，然后再持续150分钟。患者、工作人员和研究人员对这种治疗方法视而不见。主要终点是术前和术后第3天NT-proBNP水平之间的差异。分析是有意治疗。我们研究了303名患者（年龄74±7岁；女性26%，糖尿病47%），148名接受谷氨酸盐治疗组和155名对照组。与谷氨酸给药相关的主要终点没有显著差异（5390±5396 ng/L与6452±5215 ng/L；p=0.086）。与6名对照组（0.7%与3.9%；p=0.012）相比，谷氨酸组有一名患者在≤30天内死亡。未观察到与谷氨酸相关的不良事件。发现谷氨酸与糖尿病之间存在显著的相互作用（p=0.03）。在没有糖尿病的患者中，谷氨酸组的主要终点（平均4503±4846纳克/升对6824±5671纳克/升；p=0.007）和急性肾损伤的发生率（11%对29%；p=0.005）降低。在对基线数据的差异进行调整后，这些关联仍然显著。该研究的主要局限性是：（i）它依赖于心力衰竭的替代标志物；以及（ii）与用于样本量估计的队列相比，糖尿病患者的比例几乎翻了一番。结论术后输注谷氨酸并不能显著降低NT-proBNP的升高。糖尿病患者和非糖尿病患者的不同结果与先前的观察结果一致，并表明谷氨酸促进缺血后心肌恢复的概念值得进一步评估。试验注册ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT02592824.欧盟药品监管机构临床试验数据库（Eudra CT编号2011-006241-15）。
{"title":"Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II): A randomized controlled trial","authors":"J. Holm, G. Ferrari, A. Holmgren, F. Vánky, Ö. Friberg, M. Vidlund, R. Svedjeholm","doi":"10.1371/journal.pmed.1003997","DOIUrl":"https://doi.org/10.1371/journal.pmed.1003997","url":null,"abstract":"Background Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG. Methods and findings A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation. Conclusions Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation. Trial registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824. European Union Drug Regulating Authorities Clinical Trials Database (Eudra CT number 2011-006241-15).","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45101393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1003983
C. Vicens, A. Leiva, F. Bejarano, Ermengol Sempere-Verdú, R. M. Rodríguez-Rincón, F. Fiol, M. Mengual, Asunción Ajenjo-Navarro, F. Do Pazo, C. Mateu, S. Folch, Santiago Alegret, J. Coll, M. Martín-rabadan, I. Socias
Background Current benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users. Methods and findings We conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years. Intention-to-treat (ITT) analysis was used to assess all clinical outcomes. Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: −3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): −4.96, −1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was −0.36 (95% CI: −0.55, −0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was −0.87 (95% CI: −1.44, −0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents. Conclusions A multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in th
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Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1003989
S. Misra, J. Florez
In this Perspective, Shivani Misra and Jose C Florez discuss the application of precision medicine tools in under-represented populations.
从这个角度来看，Shivani Misra和Jose C Florez讨论了精准医疗工具在代表性不足人群中的应用。
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Pub Date : 2022-05-01DOI: 10.1371/journal.pmed.1004010
Plos Medicine Editors
{"title":"Call for Papers: PLOS Medicine Special Issue on the COVID-19 Pandemic and Global Mental Health","authors":"Plos Medicine Editors","doi":"10.1371/journal.pmed.1004010","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004010","url":null,"abstract":"","PeriodicalId":20368,"journal":{"name":"PLoS Medicine","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42194912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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