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Abandonment of Human Immunodeficiency Virus Preexposure Prophylaxis Prescriptions at Retail Pharmacies-United States, 2019. 2019年美国零售药店放弃人类免疫缺陷病毒暴露前预防处方。
Ya Lin A Huang, Weiming Zhu, Neal Carnes, Karen W Hoover

We analyzed a national pharmacy database to estimate the annual number of persons who abandoned preexposure prophylaxis (PrEP) prescriptions and assessed associated factors. About 9% of persons prescribed PrEP abandoned prescriptions in 2019; abandonment was associated with sex, age, insurance type, black race/ethnicity, and drug copayment amount.

我们分析了一个国家药房数据库,以估计每年放弃暴露前预防(PrEP)处方的人数,并评估了相关因素。2019年,约有9%的人放弃了PrEP处方;遗弃与性别、年龄、保险类型、黑人种族和药物共付金额有关。
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引用次数: 1
Performance of a Histidine Rich Protein-2 Based (First Response) and a p-Lactate Dehydrogenase-based (Optimal) Rapid Diagnostic Test for Diagnosis of Malaria in Patients With Pediatric Sickle Cell Disease. 基于富组氨酸蛋白-2(第一反应)和基于p-乳酸脱氢酶(最佳)的快速诊断试剂盒诊断小儿镰状细胞病疟疾的性能
George O Adjei, Abdul M Sulley, Bamenla Q Goka, Christabel Enweronu-Laryea, Lorna Renner, Michael Alifrangis, Jorgen A L Kurtzhals

Background: Rapid diagnostic tests (RDTs) have been extensively evaluated and play an important role in malaria diagnosis. However, the accuracy of RDTs for malaria diagnosis in patients with sickle cell disease (SCD) is unknown.

Methods: We compared the performance of a histidine rich protein 2 (HRP-2)-based RDT (First Response) and a lactate dehydrogenase (LDH)-based RDT (Optimal) with routine microscopy as reference standard in 445 children with SCD and an acute febrile illness in Accra, Ghana.

Results: The overall sensitivity, specificity, and positive and negative predictive values of the HRP-2-based RDTs were 100%, 95.7%, 73.8%, and 100%, respectively. Comparable values for the LDH-based RDTs were 91.7%, 99.5%, 95.7%, and 99.0%, respectively. A total of 423 results were true in both tests, 1 result was false in both tests, 16 results were false in the HRP-2 test only, and 5 were false in the LDH test only (McNemar test, P = .03). At follow-up, 73.7% (28/38), 52.6% (20/38), 48.6% (17/35), and 13.2% (5/38) of study participants were HRP-2 positive on days 14, 28, 35, and 42, respectively, compared with 0%, 2.6% (1/38), 2.9% (1/35), and 2.6% (1/38) for LDH.

Conclusion: The HRP2-based RDT fulfilled World Health Organization criteria for malaria diagnosis in patients with SCD and may provide diagnostic evidence for treatment to begin in cases in which treatment would otherwise have begun presumptively based on symptoms, whereas LDH-based RDTs may be more suitable as a confirmatory test in low-parasitemic subgroups, such as patients with SCD.

背景:快速诊断试验(RDTs)已得到广泛评价,并在疟疾诊断中发挥重要作用。然而,在镰状细胞病(SCD)患者中,rdt诊断疟疾的准确性尚不清楚。方法:我们比较了富组氨酸蛋白2 (HRP-2)为基础的RDT (First Response)和乳酸脱氢酶(LDH)为基础的RDT (Optimal)的性能,常规显微镜作为参考标准,在加纳阿克拉的445名SCD和急性发热性疾病儿童中使用。结果:基于hrp -2的rdt的总体敏感性为100%,特异性为95.7%,阳性预测值为73.8%,阴性预测值为100%。基于ldh的rdt的可比值分别为91.7%、99.5%、95.7%和99.0%。两项检测结果均为真423例,两项检测结果均为假1例,仅HRP-2检测结果为假16例,仅LDH检测结果为假5例(McNemar检验,P = .03)。在随访中,73.7%(28/38)、52.6%(20/38)、48.6%(17/35)和13.2%(5/38)的研究参与者在第14、28、35和42天分别呈HRP-2阳性,而LDH为0%、2.6%(1/38)、2.9%(1/35)和2.6%(1/38)。结论:基于hrp2的RDT符合世界卫生组织对SCD患者的疟疾诊断标准,并且可能为在根据症状推定开始治疗的病例中开始治疗提供诊断证据,而基于ldl的RDT可能更适合作为低寄生虫亚组(如SCD患者)的确证试验。
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引用次数: 2
Successful Fidaxomicin Hospital Discharges of Adult Patients With Clostridioides difficile Infections Post-2021 Guidelines: Are Economic Barriers Finally Coming Down? 2021年后,非达索霉素成功帮助艰难梭菌感染的成年患者出院:经济障碍最终会消失吗?
Noah Fang, David Ha, Kimberly Dong, Thomas Leung, Sydney Lee, Marisa Holubar, Lina Meng

We reviewed Clostridioides difficile-positive patients discharged on fidaxomicin after local adoption of 2021 C. difficile infection (CDI) guidelines. From 14 June to 3 October 2021, 80% (12/15) had copayments of $0-$35 and 27% (4/15) required prior authorization. The 30-day CDI recurrence was 7%.

我们回顾了当地采用2021年艰难梭菌感染(CDI)指南后使用非达霉素出院的艰难梭菌阳性患者。从2021年6月14日到10月3日,80%(12/15)的共付额为0- 35美元,27%(4/15)的共付额需要事先授权。30天CDI复发率为7%。
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引用次数: 0
Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure. 最佳尿培养诊断管理实践-结果从专家修改德尔菲程序。
Kimberly C Claeys, Barbara W Trautner, Surbhi Leekha, K C Coffey, Christopher J Crnich, Dan J Diekema, Mohamad G Fakih, Matthew Bidwell Goetz, Kalpana Gupta, Makoto M Jones, Luci Leykum, Stephen Y Liang, Lisa Pineles, Ashley Pleiss, Emily S Spivak, Katie J Suda, Jennifer M Taylor, Chanu Rhee, Daniel J Morgan

Background: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

Methods: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed.

Results: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions.

Conclusions: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

背景:尿培养是非特异性的,经常导致尿路感染的误诊和不必要的抗生素。诊断管理是一套程序,修改测试顺序,处理和报告,以优化诊断和下游治疗。在这项研究中,我们旨在为尿液培养诊断管理的最佳实践提供专家指导。方法:采用RAND-modified德尔菲法与多学科专家小组确定诊断管理的最佳做法。临床问题,以指导建议分为三个主题领域(订购,处理,报告)在实践设置急诊科,住院,门诊和长期护理。15位专家按照9分的李克特量表对建议进行排名。专家组在虚拟会议上讨论了未达成一致的建议,然后通过电子邮件完成了第二轮排名。经过对结果的二次审查和小组讨论,制定了一系列指导声明。结果:共审查了165个问题。专家组就104项达成了一致意见,包括18项总体指导声明。建议采用以下策略来优化尿培养的订购:要求记录症状,在没有症状的情况下发送警报以阻止订购,并取消重复培养。对于尿培养处理,条件尿培养和尿白细胞计数作为标准支持。对于尿培养报告,适当的做法包括在特定条件下推动不鼓励治疗和选择性报告抗生素以指导治疗决策。结论:这18条指导声明可以优化尿培养的使用,以获得更好的患者预后。
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引用次数: 13
Impact of Biannual Mass Azithromycin Treatment on Enteropathogen Carriage in Children <5 Years Old in Niger. 尼日尔一年两次大规模阿奇霉素治疗对5岁以下儿童肠道病原菌携带的影响
James A Platts-Mills, Elias G Ayoub, Jixian Zhang, Elizabeth T Rogawski McQuade, Ahmed M Arzika, Ramatou Maliki, Amza Abdou, Jeremy D Keenan, Thomas M Lietman, Jie Liu, Eric R Houpt

We analyzed samples obtained at baseline and 24 months in a mass azithromycin administration trial in Niger using quantitative polymerase chain reaction. In villages randomized to azithromycin, Shigella was the only pathogen reduced at 24 months (prevalence ratio, 0.36 [95% confidence interval: .17-.79]; difference in log quantity, -.42 [-.75 to -.10]).

我们使用定量聚合酶链反应分析了在尼日尔进行的大规模阿奇霉素给药试验中基线和24个月时获得的样本。在随机分配到阿奇霉素的村庄中,志贺氏菌是24个月时唯一减少的病原体(患病率为0.36[95%可信区间:0.17 - 0.79];对数量的差,-。42(-。[75至- 0.10])。
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引用次数: 1
Access to medicines for treating people with cryptococcal meningitis 获得治疗隐球菌脑膜炎患者的药物
J. Burry, C. P. Casas, N. Ford
Cryptococcal meningitis accounts for one in five AIDS-related deaths globally. WHO guidelines strongly recommend a single high-dose of liposomal amphotericin B as part of preferred treatment, but this drug remains unaffordable in most low- and middle-income countries. A proactive approach is needed from manufacturers and other stakeholders to improve access.
隐球菌脑膜炎占全球艾滋病相关死亡人数的五分之一。世卫组织指南强烈建议将单次高剂量两性霉素B脂质体作为首选治疗的一部分,但这种药物在大多数低收入和中等收入国家仍然负担不起。制造商和其他利益攸关方需要采取积极主动的方法来改善获取。
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引用次数: 5
Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients 口服抗病毒药物使用对社区COVID-19患者住院风险的影响
T. Yip, G. Lui, Mandy Sze-Man Lai, V. Wong, Y. Tse, Bosco Ma, Elsie Hui, Maria Kw Leung, H. Chan, D. S. Hui, G. Wong
ABSTRACT Background We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of non-hospitalized COVID-19 patients. Methods This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. Results Of 93,883 patients, 83,154 (88.6%), 5,808 (6.2%), and 4,921 (5.2%) were oral antiviral non-users, molnupiravir users, and nirmatrelvir/ritonavir users respectively. Compared to non-users, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1,931 (2.1%) patients were hospitalized and 225 (0.2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0.79, 95%CI 0.65-0.95, P = 0.011) but not molnupiravir use (weighted hazard ratio 1.17, 95%CI 0.99-1.39, P = 0.062) was associated with a reduced risk of hospitalization than non-users. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared to non-users. Conclusion Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world non-hospitalized COVID-19 patients.
背景:我们研究了莫努匹拉韦和尼马特利韦/利托那韦在现实世界非住院COVID-19患者队列中降低住院和死亡的有效性。方法:本研究是在香港进行的一项区域性回顾性队列研究。确定了2022年2月16日至3月31日期间在指定门诊就诊的非住院COVID-19患者。排除首次门诊预约当天住院或同时使用两种口服抗病毒药物的患者。主要终点是住院。次要终点是重症监护病房入住、有创机械通气使用和/或死亡的综合指标。结果93,883例患者中,83,154例(88.6%)、5,808例(6.2%)和4,921例(5.2%)分别为口服抗病毒药物非使用者、莫努匹拉韦使用者和尼马特利韦/利托那韦使用者。与非服用者相比,口服抗病毒药物服用者年龄更大,合并症更多,完全疫苗接种率更低,前一年住院次数更多。与尼马特里韦/利托那韦使用者相比,莫硝吡韦使用者年龄更大,合并症更多,完全疫苗接种率更低,前一年住院次数更多。中位随访时间为30天,1,931例(2.1%)患者住院,225例(0.2%)患者出现次要终点。在倾向评分加权后,尼马特利韦/利托那韦的使用(加权风险比0.79,95%CI 0.65-0.95, P = 0.011)与住院风险降低相关,而莫那匹拉韦的使用(加权风险比1.17,95%CI 0.99-1.39, P = 0.062)与住院风险降低无关。与非使用者相比,使用莫努匹拉韦或尼马特利韦/利托那韦与次要终点风险降低无关。结论:在现实世界的非住院COVID-19患者中,使用尼马特利韦/利托那韦而不使用莫努匹拉韦与住院风险降低相关。
{"title":"Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients","authors":"T. Yip, G. Lui, Mandy Sze-Man Lai, V. Wong, Y. Tse, Bosco Ma, Elsie Hui, Maria Kw Leung, H. Chan, D. S. Hui, G. Wong","doi":"10.2139/ssrn.4112160","DOIUrl":"https://doi.org/10.2139/ssrn.4112160","url":null,"abstract":"ABSTRACT Background We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of non-hospitalized COVID-19 patients. Methods This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. Results Of 93,883 patients, 83,154 (88.6%), 5,808 (6.2%), and 4,921 (5.2%) were oral antiviral non-users, molnupiravir users, and nirmatrelvir/ritonavir users respectively. Compared to non-users, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1,931 (2.1%) patients were hospitalized and 225 (0.2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0.79, 95%CI 0.65-0.95, P = 0.011) but not molnupiravir use (weighted hazard ratio 1.17, 95%CI 0.99-1.39, P = 0.062) was associated with a reduced risk of hospitalization than non-users. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared to non-users. Conclusion Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world non-hospitalized COVID-19 patients.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90859247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 40
Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review. 中和中枢神经系统和局部隐球菌病患者的抗粒细胞-巨噬细胞集落刺激因子自身抗体:纵向随访和文献综述。
Po Hsien Kuo, Un In Wu, Yi Hua Pan, Jann Tay Wang, Yu Chen Wang, Hsin Yun Sun, Wang Huei Sheng, Yee Chun Chen, Shan Chwen Chang

Background: Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course.

Methods: We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed.

Results: Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence.

Conclusions: Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.

背景:中和抗粒细胞-巨噬细胞集落刺激因子(GM-CSF)自身抗体(AAbs)已被越来越多地认识到可使健康个体易患播散性隐球菌病。然而,研究只考虑了中枢神经系统(CNS)感染的患者。没有纵向研究捕捉到疾病谱系和临床病程。方法:我们前瞻性地招募了没有人类免疫缺陷病毒感染的成年人,他们患有播散性或不寻常的隐球菌病。我们比较了人口统计学、临床特征、血清隐球菌抗原(CrAg)滴度动力学、抗gm - csf AAb浓度,以及抗gm - csf AAb患者(病例患者)和不抗gm - csf AAb患者(对照组患者)的治疗结果。还审查了文献中的其他报告。结果:23例患者入组,其中6例抗gm - csf抗体阳性。所有真菌培养阳性的患者(5/5[100%])均感染了加蒂隐球菌VGII。其中3例仅为肺部受累,1例仅为肌肉骨骼病变。中枢神经系统隐球菌病患者血清抗gm - csf抗体浓度高于神经外隐球菌病患者。与对照组相比,病例患者血清CrAg初始和峰值水平较高,抗原血症持续时间较长。所有完成抗真菌治疗的患者预后良好,无复发。结论:不仅对既往健康的播散性隐球菌病患者,对不明原因的局部隐球菌病患者也应考虑检测抗gm - csf抗体。尽管抗gm - csf单抗持续存在,但完成抗真菌治疗后复发的情况很少。
{"title":"Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review.","authors":"Po Hsien Kuo, Un In Wu, Yi Hua Pan, Jann Tay Wang, Yu Chen Wang, Hsin Yun Sun, Wang Huei Sheng, Yee Chun Chen, Shan Chwen Chang","doi":"10.1093/cid/ciab920","DOIUrl":"10.1093/cid/ciab920","url":null,"abstract":"<p><strong>Background: </strong>Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course.</p><p><strong>Methods: </strong>We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed.</p><p><strong>Results: </strong>Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence.</p><p><strong>Conclusions: </strong>Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"278-287"},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39577334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Post-Vaccination Coronavirus Disease 2019: A Case-Control Study and Genomic Analysis of 119 Breakthrough Infections in Partially Vaccinated Individuals. 疫苗接种后冠状病毒病2019:部分疫苗接种个体119例突破性感染的病例对照研究和基因组分析
Ioannis Baltas, Florencia A T Boshier, Charlotte A Williams, Nadua Bayzid, Marius Cotic, José Afonso Guerra-Assunção, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Sunando Roy, Rachel Williams, Judith Breuer, Tabitha W Mahungu

Background: Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic.

Methods: We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020-March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed.

Results: Overall, 116 of 119 cases developed COVID-19 post-first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P < .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (-1.89 days; 95% CI: -4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage).

Conclusions: Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.

背景:疫苗接种后感染对2019冠状病毒病(COVID-19)大流行的控制构成挑战。方法:将119例接种疫苗后BNT162b2 mRNA或ChAdOx1 nCOV-19感染病例与476例未接种疫苗的COVID-19患者(2020年9月- 2021年3月)按年龄和性别进行匹配。评估60天全因死亡率、住院率和住院时间的差异。系统发育、单核苷酸多态性(SNP)和少数变异等位基因(MVA)全基因组测序分析。结果:总体而言,119例病例中有116例在首次接种疫苗后(中位数为14天)发生COVID-19。119例病例中有13例(10.9%)死亡,476例对照中有158例(33.2%)死亡(P结论:当B.1.1.7为主要谱系时,既往接种疫苗可降低死亡率。在系统发育、SNP和MVA分析中未检测到明显的谱系特异性基因组变化。
{"title":"Post-Vaccination Coronavirus Disease 2019: A Case-Control Study and Genomic Analysis of 119 Breakthrough Infections in Partially Vaccinated Individuals.","authors":"Ioannis Baltas,&nbsp;Florencia A T Boshier,&nbsp;Charlotte A Williams,&nbsp;Nadua Bayzid,&nbsp;Marius Cotic,&nbsp;José Afonso Guerra-Assunção,&nbsp;Dianne Irish-Tavares,&nbsp;Tanzina Haque,&nbsp;Jennifer Hart,&nbsp;Sunando Roy,&nbsp;Rachel Williams,&nbsp;Judith Breuer,&nbsp;Tabitha W Mahungu","doi":"10.1093/cid/ciab714","DOIUrl":"https://doi.org/10.1093/cid/ciab714","url":null,"abstract":"<p><strong>Background: </strong>Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic.</p><p><strong>Methods: </strong>We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020-March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed.</p><p><strong>Results: </strong>Overall, 116 of 119 cases developed COVID-19 post-first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P < .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (-1.89 days; 95% CI: -4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage).</p><p><strong>Conclusions: </strong>Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":" ","pages":"305-313"},"PeriodicalIF":11.8,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39337910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Disease Progression in Patients With Nontuberculous Mycobacterial Lung Disease of Nodular Bronchiectatic (NB) Pattern: The Roles of Cavitary NB and Soluble Programmed Death Protein-1. 结节性支气管扩张(NB)型非结核分枝杆菌肺病患者的疾病进展:空腔NB和可溶性程序性死亡蛋白-1的作用
Sheng Wei Pan, Wei Juin Su, Yu Jiun Chan, Mei Lin Ho, Jia Yih Feng, Chin Chung Shu, Jann Yuan Wang, Hao Chien Wang, Chong Jen Yu, Yuh Min Chen

Background: In patients with nodular bronchiectatic (NB) nontuberculous mycobacterial lung disease (NTM-LD), risk factors for disease progression have not been clearly investigated. The roles of cavitary NB and soluble programmed death protein-1 (sPD-1), an immune-related biomarker, in the disease course of NB NTM-LD remain unknown.

Methods: Patients with NB NTM-LD were enrolled from 2 medical centers in 2014-2020. We identified cavitary NB, measured sPD-1 levels, and analyzed factors associated with cavitary NB and predictors for disease progression of NB NTM-LD.

Results: Of 120 cases of NB NTM-LD, 87 (72.5%) were caused by Mycobacterium avium complex. sPD-1 levels were lower in 13 (10.8%) patients with cavitary NB than in noncavitary patients (P = .020). Over 1.41 ± 1.43 years of follow-up, 12 (92.3%) patients in the cavitary and 66 (61.7%) in the noncavitary group developed disease progression (P = .032). In multivariable analysis, body mass index (BMI [kg/m2]; adjusted hazard ratio [aHR], .895 [95% confidence interval, .811-.988]), sputum smear grade (aHR, 1.247 [1.014-1.534]), cavitary NB (aHR, 2.008 [1.052-3.834]), and sPD-1 (per 10-pg/mL increase; aHR, .889 [.816-.967]) were predictive for disease progression. Notably, sPD-1 showed a dose-dependent association with disease progression (sPD-1 ≤23.5 pg/mL; aHR, 3.306 [1.664-6.567]; sPD-1: 23.6-53.7 pg/mL; aHR, 2.496 [1.390-4.483]) compared with the reference (sPD-1 >53.7 pg/mL).

Conclusions: Patients with NB NTM-LD and low sPD-1, low BMI, high smear grade, and cavitary NB were at high risk for disease progression. sPD-1 was low in patients with cavitary NB phenotype and dose-responsively associated with disease progression.

背景:在结节性支气管扩张(NB)非结核性分枝杆菌肺病(NTM-LD)患者中,疾病进展的危险因素尚未明确调查。空腔NB和可溶性程序性死亡蛋白-1(一种免疫相关生物标志物)在NB - NTM-LD疾病过程中的作用尚不清楚。方法:选取2014-2020年2个医疗中心NB - NTM-LD患者。我们确定了空腔NB,测量了sPD-1水平,并分析了与空腔NB相关的因素和NB NTM-LD疾病进展的预测因素。结果:120例NB - NTM-LD中,87例(72.5%)由鸟分枝杆菌复合体引起。13例(10.8%)空腔NB患者的sPD-1水平低于非空腔NB患者(P = 0.020)。在1.41±1.43年的随访中,腔室组12例(92.3%),非腔室组66例(61.7%)出现疾病进展(P = 0.032)。在多变量分析中,体重指数(BMI [kg/m2];校正风险比[aHR], 0.895[95%可信区间,0.811 - 0.988]),痰涂片分级(aHR, 1.247[1.014-1.534]),腔内NB (aHR, 2.008 [1.052-3.834]), sPD-1(每10 pg/mL升高;aHR(.889[.816-.967])预测疾病进展。值得注意的是,sPD-1与疾病进展呈剂量依赖性关联(sPD-1≤23.5 pg/mL;aHR, 3.306 [1.664-6.567];sPD-1: 23.6-53.7 pg/mL;aHR为2.496[1.390-4.483]),与参比(sPD-1 >53.7 pg/mL)比较。结论:NB - NTM-LD合并低sPD-1、低BMI、高涂片分级和空腔NB的患者有较高的疾病进展风险。在空腔NB表型患者中sPD-1较低,且与疾病进展呈剂量反应性相关。
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引用次数: 5
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Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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