Pub Date : 2024-12-06DOI: 10.1016/S2214-109X(24)00532-1
{"title":"Correction to Lancet Glob Health 2024; published online Dec 5. https://doi.org/10.1016/S2214-109X(24)00525-4.","authors":"","doi":"10.1016/S2214-109X(24)00532-1","DOIUrl":"10.1016/S2214-109X(24)00532-1","url":null,"abstract":"","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802911","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 : 2024-12-06DOI: 10.1016/S2214-109X(24)00533-3
{"title":"Correction to Lancet Glob Health 2024; 12: e1232-43.","authors":"","doi":"10.1016/S2214-109X(24)00533-3","DOIUrl":"https://doi.org/10.1016/S2214-109X(24)00533-3","url":null,"abstract":"","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":" ","pages":""},"PeriodicalIF":19.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802910","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 : 2024-12-05DOI: 10.1016/s2214-109x(24)00525-4
The Lancet Global Health
{"title":"Harm reduction must replace punitive drug policies","authors":"The Lancet Global Health","doi":"10.1016/s2214-109x(24)00525-4","DOIUrl":"https://doi.org/10.1016/s2214-109x(24)00525-4","url":null,"abstract":"","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":"68 1","pages":""},"PeriodicalIF":34.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790067","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 : 2024-12-01Epub Date: 2024-11-11DOI: 10.1016/S2214-109X(24)00418-2
Amy Sarah Ginsburg, Ken Duncan, Keith P Klugman, Padmini Srikantiah
{"title":"Access to antibiotics for pneumonia and sepsis in LMICs.","authors":"Amy Sarah Ginsburg, Ken Duncan, Keith P Klugman, Padmini Srikantiah","doi":"10.1016/S2214-109X(24)00418-2","DOIUrl":"10.1016/S2214-109X(24)00418-2","url":null,"abstract":"","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":" ","pages":"e1928-e1929"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630521","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 : 2024-12-01Epub Date: 2024-10-17DOI: 10.1016/S2214-109X(24)00447-9
Abubakar Umar, Catherine E Oldenburg
{"title":"Strengthening health-care systems to reduce child mortality.","authors":"Abubakar Umar, Catherine E Oldenburg","doi":"10.1016/S2214-109X(24)00447-9","DOIUrl":"10.1016/S2214-109X(24)00447-9","url":null,"abstract":"","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":" ","pages":"e1919-e1920"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478325","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 : 2024-12-01DOI: 10.1016/S2214-109X(24)00376-0
Jacob Dubner, Alfred I Neugut, Maureen Joffe, Daniel S O'Neil, Oluwatosin A Ayeni, Wenlong Carl Chen, Ines Buccimazza, Sharon R Čačala, Laura W Stopforth, Hayley A Farrow, Sarah Nietz, Nivashini Murugan, Boitumelo Phakathi, Judith S Jacobson, Katherine D Crew, Valerie McCormack, Paul Ruff, Herbert Cubasch, Yoanna S Pumpalova
Background: Breast cancer is the most common malignancy diagnosed among women in South Africa, with the aggressive triple-negative subtype comprising approximately 15% of breast cancers in this population. South Africa has the largest population of people with HIV in the world. This study aims to evaluate the association between HIV status and the proportion of patients with breast cancer with the triple-negative subtype.
Methods: We did a cross-sectional analysis of case-only data from the South African Breast Cancer and HIV Outcomes (SABCHO) study, a prospective cohort study recruiting patients with newly diagnosed breast cancer at six public hospitals in South Africa. We analysed data from patients who enrolled in SABCHO between Jan 1, 2015, and Jan 18, 2022. Women aged 18 years or older with newly diagnosed and histologically confirmed invasive breast cancer were eligible. Participants were classified as HIV-positive or HIV-negative by use of an ELISA-based HIV test done at the time of enrolment. We developed multivariable logistic regression models to test for an association between HIV status and the proportion of triple-negative relative to non-triple-negative breast cancers while adjusting for demographic and reproductive risk factors.
Findings: Of the 4122 patients enrolled in the SABCHO cohort within our study timeframe, 239 patients were excluded due to unknown breast cancer subtype (n=141), HIV status (n=97), or race (n=1). 3883 women with breast cancer were included in the study, of whom 637 (16·4%) had triple-negative breast cancer, 894 (23·0%) were HIV-positive, and 186 (4·8%) had triple-negative breast cancer and HIV. Triple-negative breast cancer accounted for 186 (20·8%) of 894 breast cancers among women who were HIV-positive and 451 (15·1%) of 2989 breast cancers among women who were HIV-negative (p<0·0001). In the fully adjusted logistic regression model, HIV-positive status was associated with an increased proportion of triple-negative breast cancer (adjusted odds ratio [OR] 1·39, 95% CI 1·12-1·74, compared with women who were HIV-negative). When compared with women who were HIV-negative, the association between HIV-positive status and the proportion of triple-negative breast cancer was strongest among the subgroup of women with a duration of HIV infection of 2 years or longer (1·57, 1·23-2·00) and those on antiretroviral therapy (ART; 1·47, 1·16-1·87).
Interpretation: Patients with breast cancer and chronic HIV who are on ART are more likely to have triple-negative breast cancer than patients with breast cancer without HIV. This association is independent of age, race, and reproductive factors.
Funding: US National Institutes of Health, University of the Witwatersrand, South Africa Medical Research Council Common Epithelial Cancers Research Center, Conquer Cancer Foundation, and Varmus Global Scholars Fund.
背景乳腺癌是南非妇女中最常见的恶性肿瘤，其中侵袭性三阴性亚型乳腺癌约占该人群乳腺癌的 15%。南非是世界上艾滋病毒感染者人数最多的国家。本研究旨在评估 HIV 感染状况与三阴性亚型乳腺癌患者比例之间的关系：我们对南非乳腺癌与 HIV 结果（SABCHO）研究中的病例数据进行了横断面分析，该研究是一项前瞻性队列研究，招募了南非六家公立医院的新诊断乳腺癌患者。我们分析了 2015 年 1 月 1 日至 2022 年 1 月 18 日期间加入 SABCHO 的患者数据。年龄在 18 岁或以上、新诊断并经组织学证实患有浸润性乳腺癌的女性均符合条件。通过在注册时进行的基于 ELISA 的 HIV 检测，参与者被分为 HIV 阳性或 HIV 阴性。我们建立了多变量逻辑回归模型，以检验艾滋病病毒感染状况与三阴性乳腺癌比例（相对于非三阴性乳腺癌）之间是否存在关联，同时对人口和生殖风险因素进行了调整：在我们的研究时间范围内，SABCHO队列共登记了4122名患者，其中239名患者因乳腺癌亚型不明（141人）、HIV感染状况不明（97人）或种族不明（1人）而被排除在外。研究共纳入了 3883 名乳腺癌妇女，其中 637 人（16-4%）患有三阴性乳腺癌，894 人（23-0%）为 HIV 阳性，186 人（4-8%）患有三阴性乳腺癌和 HIV。在艾滋病毒呈阳性的 894 名女性乳腺癌患者中，三阴性乳腺癌占 186 例（20-8%），在艾滋病毒呈阴性的 2989 名女性乳腺癌患者中，三阴性乳腺癌占 451 例（15-1%）（p解释：与未感染艾滋病病毒的乳腺癌患者相比，接受抗逆转录病毒疗法的慢性艾滋病病毒感染者更有可能罹患三阴性乳腺癌。这种关联与年龄、种族和生殖因素无关：美国国立卫生研究院、威特沃特斯兰德大学、南非医学研究委员会常见上皮癌研究中心、征服癌症基金会和瓦尔穆斯全球学者基金。
{"title":"The association of HIV status with triple-negative breast cancer in patients with breast cancer in South Africa: a cross-sectional analysis of case-only data from a prospective cohort study.","authors":"Jacob Dubner, Alfred I Neugut, Maureen Joffe, Daniel S O'Neil, Oluwatosin A Ayeni, Wenlong Carl Chen, Ines Buccimazza, Sharon R Čačala, Laura W Stopforth, Hayley A Farrow, Sarah Nietz, Nivashini Murugan, Boitumelo Phakathi, Judith S Jacobson, Katherine D Crew, Valerie McCormack, Paul Ruff, Herbert Cubasch, Yoanna S Pumpalova","doi":"10.1016/S2214-109X(24)00376-0","DOIUrl":"10.1016/S2214-109X(24)00376-0","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common malignancy diagnosed among women in South Africa, with the aggressive triple-negative subtype comprising approximately 15% of breast cancers in this population. South Africa has the largest population of people with HIV in the world. This study aims to evaluate the association between HIV status and the proportion of patients with breast cancer with the triple-negative subtype.</p><p><strong>Methods: </strong>We did a cross-sectional analysis of case-only data from the South African Breast Cancer and HIV Outcomes (SABCHO) study, a prospective cohort study recruiting patients with newly diagnosed breast cancer at six public hospitals in South Africa. We analysed data from patients who enrolled in SABCHO between Jan 1, 2015, and Jan 18, 2022. Women aged 18 years or older with newly diagnosed and histologically confirmed invasive breast cancer were eligible. Participants were classified as HIV-positive or HIV-negative by use of an ELISA-based HIV test done at the time of enrolment. We developed multivariable logistic regression models to test for an association between HIV status and the proportion of triple-negative relative to non-triple-negative breast cancers while adjusting for demographic and reproductive risk factors.</p><p><strong>Findings: </strong>Of the 4122 patients enrolled in the SABCHO cohort within our study timeframe, 239 patients were excluded due to unknown breast cancer subtype (n=141), HIV status (n=97), or race (n=1). 3883 women with breast cancer were included in the study, of whom 637 (16·4%) had triple-negative breast cancer, 894 (23·0%) were HIV-positive, and 186 (4·8%) had triple-negative breast cancer and HIV. Triple-negative breast cancer accounted for 186 (20·8%) of 894 breast cancers among women who were HIV-positive and 451 (15·1%) of 2989 breast cancers among women who were HIV-negative (p<0·0001). In the fully adjusted logistic regression model, HIV-positive status was associated with an increased proportion of triple-negative breast cancer (adjusted odds ratio [OR] 1·39, 95% CI 1·12-1·74, compared with women who were HIV-negative). When compared with women who were HIV-negative, the association between HIV-positive status and the proportion of triple-negative breast cancer was strongest among the subgroup of women with a duration of HIV infection of 2 years or longer (1·57, 1·23-2·00) and those on antiretroviral therapy (ART; 1·47, 1·16-1·87).</p><p><strong>Interpretation: </strong>Patients with breast cancer and chronic HIV who are on ART are more likely to have triple-negative breast cancer than patients with breast cancer without HIV. This association is independent of age, race, and reproductive factors.</p><p><strong>Funding: </strong>US National Institutes of Health, University of the Witwatersrand, South Africa Medical Research Council Common Epithelial Cancers Research Center, Conquer Cancer Foundation, and Varmus Global Scholars Fund.</p>","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":"12 12","pages":"e1993-e2002"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-04DOI: 10.1016/S2214-109X(24)00327-9
Yiying Cai, Suchart Booraphun, Andrew Yunkai Li, Gyan Kayastha, Paul Anantharajah Tambyah, Ben S Cooper, Nicholas Graves, Yin Mo
Background: The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia recurrence in patients with ventilator-associated pneumonia (VAP). We aimed to assess the cost-effectiveness of an individualised shortened antibiotic therapy approach in this planned economic analysis.
Methods: REGARD-VAP was a phase 4, multicentre, open-label, randomised trial to assess a short-course antibiotic treatment strategy for treatment of VAP. In this planned economic analysis, we fitted a decision tree with data from the REGARD-VAP trial to estimate the cost-effectiveness of individualised short-course therapy for VAP, compared to usual care from the health system perspective, in Nepal, Singapore, and Thailand. Incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits with 95% uncertainty intervals (UIs) were reported against relevant willingness-to-pay thresholds. Parameter uncertainties were evaluated using scenario analyses. A value of information analysis was conducted.
Findings: Adopting individualised short-course therapy was cost-effective for Nepal (ICER=US$1086; percentage cost-effectiveness=50·3%), Singapore (ICER=-$6069; percentage cost-effectiveness=55·2%), and Thailand (ICER=$263; percentage cost-effectiveness=60·5%). The associated incremental net monetary benefits were $41 (95% UI -2308 to 2390) in Nepal, $5156 (-45 805 to 56 117) in Singapore, and $804 (-6245 to 7852) in Thailand. Value of information analysis showed that reducing uncertainties for mortality probabilities, bed-day costs, and variable costs were valuable for decision making.
Interpretation: We found that an individualised short-course antibiotics strategy in patients with VAP is likely to be cost-effective in high-income, middle-income, and low-income settings, although with evident uncertainty. Considered alongside the positive externalities of reduced antimicrobial use, our findings foster confidence in policy makers contemplating adoption of short-course antibiotics.
Funding: UK Medical Research Council, Singapore National Medical Research Council, and Wellcome Trust.
{"title":"Cost-effectiveness of a short-course antibiotic treatment strategy for the treatment of ventilator-associated pneumonia: an economic analysis of the REGARD-VAP trial.","authors":"Yiying Cai, Suchart Booraphun, Andrew Yunkai Li, Gyan Kayastha, Paul Anantharajah Tambyah, Ben S Cooper, Nicholas Graves, Yin Mo","doi":"10.1016/S2214-109X(24)00327-9","DOIUrl":"10.1016/S2214-109X(24)00327-9","url":null,"abstract":"<p><strong>Background: </strong>The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia recurrence in patients with ventilator-associated pneumonia (VAP). We aimed to assess the cost-effectiveness of an individualised shortened antibiotic therapy approach in this planned economic analysis.</p><p><strong>Methods: </strong>REGARD-VAP was a phase 4, multicentre, open-label, randomised trial to assess a short-course antibiotic treatment strategy for treatment of VAP. In this planned economic analysis, we fitted a decision tree with data from the REGARD-VAP trial to estimate the cost-effectiveness of individualised short-course therapy for VAP, compared to usual care from the health system perspective, in Nepal, Singapore, and Thailand. Incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits with 95% uncertainty intervals (UIs) were reported against relevant willingness-to-pay thresholds. Parameter uncertainties were evaluated using scenario analyses. A value of information analysis was conducted.</p><p><strong>Findings: </strong>Adopting individualised short-course therapy was cost-effective for Nepal (ICER=US$1086; percentage cost-effectiveness=50·3%), Singapore (ICER=-$6069; percentage cost-effectiveness=55·2%), and Thailand (ICER=$263; percentage cost-effectiveness=60·5%). The associated incremental net monetary benefits were $41 (95% UI -2308 to 2390) in Nepal, $5156 (-45 805 to 56 117) in Singapore, and $804 (-6245 to 7852) in Thailand. Value of information analysis showed that reducing uncertainties for mortality probabilities, bed-day costs, and variable costs were valuable for decision making.</p><p><strong>Interpretation: </strong>We found that an individualised short-course antibiotics strategy in patients with VAP is likely to be cost-effective in high-income, middle-income, and low-income settings, although with evident uncertainty. Considered alongside the positive externalities of reduced antimicrobial use, our findings foster confidence in policy makers contemplating adoption of short-course antibiotics.</p><p><strong>Funding: </strong>UK Medical Research Council, Singapore National Medical Research Council, and Wellcome Trust.</p>","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":" ","pages":"e2059-e2067"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/S2214-109X(24)00357-7
Bianca Sossen, Rita Székely, Madalo Mukoka, Monde Muyoyeta, Elizabeth Nakabugo, Jerry Hella, Hung Van Nguyen, Sasiwimol Ubolyam, Berra Erkosar, Marcia Vermeulen, Chad M Centner, Sarah Nyangu, Nsala Sanjase, Mohamed Sasamalo, Huong Thi Dinh, The Anh Ngo, Weerawat Manosuthi, Supunnee Jirajariyavej, Nhung Viet Nguyen, Anchalee Avihingsanon, Andrew D Kerkhoff, Claudia M Denkinger, Klaus Reither, Lydia Nakiyingi, Peter MacPherson, Graeme Meintjes, Morten Ruhwald
<p><strong>Background: </strong>Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott).</p><p><strong>Methods: </strong>In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete.</p><p><strong>Findings: </strong>Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment.</p><p><strong>Funding: </strong>Global Health Innovative Technology Fund, KfW Development B
{"title":"Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study.","authors":"Bianca Sossen, Rita Székely, Madalo Mukoka, Monde Muyoyeta, Elizabeth Nakabugo, Jerry Hella, Hung Van Nguyen, Sasiwimol Ubolyam, Berra Erkosar, Marcia Vermeulen, Chad M Centner, Sarah Nyangu, Nsala Sanjase, Mohamed Sasamalo, Huong Thi Dinh, The Anh Ngo, Weerawat Manosuthi, Supunnee Jirajariyavej, Nhung Viet Nguyen, Anchalee Avihingsanon, Andrew D Kerkhoff, Claudia M Denkinger, Klaus Reither, Lydia Nakiyingi, Peter MacPherson, Graeme Meintjes, Morten Ruhwald","doi":"10.1016/S2214-109X(24)00357-7","DOIUrl":"10.1016/S2214-109X(24)00357-7","url":null,"abstract":"<p><strong>Background: </strong>Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott).</p><p><strong>Methods: </strong>In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete.</p><p><strong>Findings: </strong>Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment.</p><p><strong>Funding: </strong>Global Health Innovative Technology Fund, KfW Development B","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":"12 12","pages":"e2024-2034"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/S2214-109X(24)00378-4
Elizabeth T Rogawski McQuade, Stephanie A Brennhofer, Sarah E Elwood, Joseph A Lewnard, Jie Liu, Eric R Houpt, James A Platts-Mills
Background: Vaccines for diarrhoea could have the ancillary benefit of preventing antibiotic use. We aimed to quantify and compare the expected impact of enteric vaccines on antibiotic use via Monte Carlo simulations.
Methods: We analysed data from a longitudinal birth cohort, which enrolled children from 2009 to 2012 from Bangladesh, India, Nepal, Pakistan, and Tanzania. We used Monte Carlo simulations to estimate hypothetical vaccine impact in nine vaccination scenarios (including six single vaccines and three combination vaccines) on antibiotic- treated diarrhoea, overall antibiotic courses, and antibiotic exposures to bystander pathogens. For each vaccine scenario, we randomly selected target pathogen-specific diarrhoea episodes to be prevented according to the specified vaccine efficacy and estimated the absolute and relative differences in incidence of antibiotic use outcomes between vaccine and no vaccine scenarios.
Findings: Among 1119 children, there were 3029 (135·3 courses per 100 child-years) antibiotic-treated diarrhoea episodes. Based on simulated results, a Shigella vaccine would cause the greatest reductions compared with the other single pathogen vaccines in antibiotic courses for all-cause diarrhoea (6·1% relative reduction; -8·2 courses per 100 child-years [95% CI -9·4 to -7·2]), antibiotic courses overall (1·0% relative reduction; -8·2 courses per 100 child-years [-9·4 to -7·2]), and antibiotic exposures to bystander pathogens (1·2% relative reduction; -15·9 courses per 100 child-years [-18·5 to -13·8]). An adenovirus-norovirus-rotavirus vaccine would cause the greatest reductions in antibiotic use (12·2 courses per 100 child-years [-13·7 to -11·0]) compared with the other combination vaccines. However, projected vaccine effects on antibiotic use in 2021 were 45-74% smaller than those estimated in 2009-12 accounting for reductions in diarrhoea incidence in the past decade.
Interpretation: Vaccines for enteric pathogens could result in up to 8-12 prevented courses of antibiotics per 100 vaccinated children per year. Combination vaccines will probably be necessary to achieve greater than 1% reductions in total antibiotic use among children in similar low-resource settings.
Funding: Wellcome Trust and Bill & Melinda Gates Foundation.
{"title":"The impact of vaccines for diarrhoea on antibiotic use among children in five low-resource settings: a comparative simulation study.","authors":"Elizabeth T Rogawski McQuade, Stephanie A Brennhofer, Sarah E Elwood, Joseph A Lewnard, Jie Liu, Eric R Houpt, James A Platts-Mills","doi":"10.1016/S2214-109X(24)00378-4","DOIUrl":"10.1016/S2214-109X(24)00378-4","url":null,"abstract":"<p><strong>Background: </strong>Vaccines for diarrhoea could have the ancillary benefit of preventing antibiotic use. We aimed to quantify and compare the expected impact of enteric vaccines on antibiotic use via Monte Carlo simulations.</p><p><strong>Methods: </strong>We analysed data from a longitudinal birth cohort, which enrolled children from 2009 to 2012 from Bangladesh, India, Nepal, Pakistan, and Tanzania. We used Monte Carlo simulations to estimate hypothetical vaccine impact in nine vaccination scenarios (including six single vaccines and three combination vaccines) on antibiotic- treated diarrhoea, overall antibiotic courses, and antibiotic exposures to bystander pathogens. For each vaccine scenario, we randomly selected target pathogen-specific diarrhoea episodes to be prevented according to the specified vaccine efficacy and estimated the absolute and relative differences in incidence of antibiotic use outcomes between vaccine and no vaccine scenarios.</p><p><strong>Findings: </strong>Among 1119 children, there were 3029 (135·3 courses per 100 child-years) antibiotic-treated diarrhoea episodes. Based on simulated results, a Shigella vaccine would cause the greatest reductions compared with the other single pathogen vaccines in antibiotic courses for all-cause diarrhoea (6·1% relative reduction; -8·2 courses per 100 child-years [95% CI -9·4 to -7·2]), antibiotic courses overall (1·0% relative reduction; -8·2 courses per 100 child-years [-9·4 to -7·2]), and antibiotic exposures to bystander pathogens (1·2% relative reduction; -15·9 courses per 100 child-years [-18·5 to -13·8]). An adenovirus-norovirus-rotavirus vaccine would cause the greatest reductions in antibiotic use (12·2 courses per 100 child-years [-13·7 to -11·0]) compared with the other combination vaccines. However, projected vaccine effects on antibiotic use in 2021 were 45-74% smaller than those estimated in 2009-12 accounting for reductions in diarrhoea incidence in the past decade.</p><p><strong>Interpretation: </strong>Vaccines for enteric pathogens could result in up to 8-12 prevented courses of antibiotics per 100 vaccinated children per year. Combination vaccines will probably be necessary to achieve greater than 1% reductions in total antibiotic use among children in similar low-resource settings.</p><p><strong>Funding: </strong>Wellcome Trust and Bill & Melinda Gates Foundation.</p>","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":"12 12","pages":"e1954-e1961"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/S2214-109X(24)00381-4
Isaac Ravi Brenner, Clare F Flanagan, Martina Penazzato, Karen A Webb, Stephanie B Horsfall, Emily P Hyle, Elaine Abrams, Jason Bacha, Anne M Neilan, Intira Jeannie Collins, Sophie Desmonde, Siobhan Crichton, Mary-Ann Davies, Kenneth A Freedberg, Andrea L Ciaranello
<p><strong>Background: </strong>For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value.</p><p><strong>Methods: </strong>We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir-lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine-lamivudine-dolutegravir was more effective than abacavir-lamivudine-dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita.</p><p><strong>Findings: </strong>Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine-lamivudine-dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy.</p><p><strong>Interpretation: </strong>For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART.</p><p><strong>Funding: </strong>The Eunice Kenne
{"title":"Cost-effectiveness of viral load testing for transitioning antiretroviral therapy-experienced children to dolutegravir in South Africa: a modelling analysis.","authors":"Isaac Ravi Brenner, Clare F Flanagan, Martina Penazzato, Karen A Webb, Stephanie B Horsfall, Emily P Hyle, Elaine Abrams, Jason Bacha, Anne M Neilan, Intira Jeannie Collins, Sophie Desmonde, Siobhan Crichton, Mary-Ann Davies, Kenneth A Freedberg, Andrea L Ciaranello","doi":"10.1016/S2214-109X(24)00381-4","DOIUrl":"10.1016/S2214-109X(24)00381-4","url":null,"abstract":"<p><strong>Background: </strong>For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value.</p><p><strong>Methods: </strong>We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir-lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine-lamivudine-dolutegravir was more effective than abacavir-lamivudine-dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita.</p><p><strong>Findings: </strong>Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine-lamivudine-dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy.</p><p><strong>Interpretation: </strong>For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART.</p><p><strong>Funding: </strong>The Eunice Kenne","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":"12 12","pages":"e2068-e2079"},"PeriodicalIF":19.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693417","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}
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