Pub Date : 2024-07-30eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004426
Meena Rafiq, Cristina Renzi, Becky White, Nadine Zakkak, Brian Nicholson, Georgios Lyratzopoulos, Matthew Barclay
Background: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms.
Methods and findings: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use.
Conclusions: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Fu
{"title":"Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: A population-based cohort study of 477,870 patients in England.","authors":"Meena Rafiq, Cristina Renzi, Becky White, Nadine Zakkak, Brian Nicholson, Georgios Lyratzopoulos, Matthew Barclay","doi":"10.1371/journal.pmed.1004426","DOIUrl":"10.1371/journal.pmed.1004426","url":null,"abstract":"<p><strong>Background: </strong>Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms.</p><p><strong>Methods and findings: </strong>Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use.</p><p><strong>Conclusions: </strong>In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Fu","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004426"},"PeriodicalIF":15.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856916","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}
Background: Long-term care facilities (LTCFs) are hotspots for pathogen transmission. Infection control interventions are essential, but the high density and heterogeneity of interindividual contacts within LTCF may hinder their efficacy. Here, we explore how the patient-staff contact structure may inform effective intervention implementation.
Methods and findings: Using an individual-based model (IBM), we reproduced methicillin-resistant Staphylococcus aureus colonisation transmission dynamics over a detailed contact network recorded within a French LTCF of 327 patients and 263 staff over 3 months. Simulated baseline cumulative colonisation incidence was 21 patients (prediction interval: 11, 31) and 35 staff (prediction interval: 19, 54). We examined the potential impact of 3 types of interventions against transmission (reallocation reducing the number of unique contacts per staff, reinforced contact precautions, and hypothetical vaccination protecting against acquisition), targeted towards specific populations. All 3 interventions were effective when applied to all nurses or healthcare assistants (median reduction in MRSA colonisation incidence up to 35%), but the benefit did not exceed 8% when targeting any other single staff category. We identified "supercontactor" individuals with most contacts ("frequency-based," overrepresented among nurses, porters, and rehabilitation staff) or with the longest cumulative time spent in contact ("duration-based," overrepresented among healthcare assistants and patients in elderly care or persistent vegetative state (PVS)). Targeting supercontactors enhanced interventions against pathogen spread in the LTCF. With contact precautions, targeting frequency-based staff supercontactors led to the highest incidence reduction (20%, 95% CI: 19, 21). Vaccinating a mix of frequency- and duration-based staff supercontactors led to a higher reduction (23%, 95% CI: 22, 24) than all other approaches. Although based on data from a single LTCF, when varying epidemiological parameters to extend to other pathogens, our results suggest that targeting supercontactors is always the most effective strategy, indicating this approach could be applied to prevent transmission of other nosocomial pathogens.
Conclusions: By characterising the contact structure in hospital settings and identifying the categories of staff and patients more likely to be supercontactors, with either more or longer contacts than others, interventions against nosocomial spread could be more effective. We find that the most efficient implementation strategy depends on the intervention (reallocation, contact precautions, vaccination) and target population (staff, patients, supercontactors). Importantly, both staff and patients may be supercontactors, highlighting the importance of including patients in measures to prevent pathogen transmission in LTCF.
{"title":"Using contact network dynamics to implement efficient interventions against pathogen spread in hospital settings: A modelling study.","authors":"Quentin J Leclerc, Audrey Duval, Didier Guillemot, Lulla Opatowski, Laura Temime","doi":"10.1371/journal.pmed.1004433","DOIUrl":"10.1371/journal.pmed.1004433","url":null,"abstract":"<p><strong>Background: </strong>Long-term care facilities (LTCFs) are hotspots for pathogen transmission. Infection control interventions are essential, but the high density and heterogeneity of interindividual contacts within LTCF may hinder their efficacy. Here, we explore how the patient-staff contact structure may inform effective intervention implementation.</p><p><strong>Methods and findings: </strong>Using an individual-based model (IBM), we reproduced methicillin-resistant Staphylococcus aureus colonisation transmission dynamics over a detailed contact network recorded within a French LTCF of 327 patients and 263 staff over 3 months. Simulated baseline cumulative colonisation incidence was 21 patients (prediction interval: 11, 31) and 35 staff (prediction interval: 19, 54). We examined the potential impact of 3 types of interventions against transmission (reallocation reducing the number of unique contacts per staff, reinforced contact precautions, and hypothetical vaccination protecting against acquisition), targeted towards specific populations. All 3 interventions were effective when applied to all nurses or healthcare assistants (median reduction in MRSA colonisation incidence up to 35%), but the benefit did not exceed 8% when targeting any other single staff category. We identified \"supercontactor\" individuals with most contacts (\"frequency-based,\" overrepresented among nurses, porters, and rehabilitation staff) or with the longest cumulative time spent in contact (\"duration-based,\" overrepresented among healthcare assistants and patients in elderly care or persistent vegetative state (PVS)). Targeting supercontactors enhanced interventions against pathogen spread in the LTCF. With contact precautions, targeting frequency-based staff supercontactors led to the highest incidence reduction (20%, 95% CI: 19, 21). Vaccinating a mix of frequency- and duration-based staff supercontactors led to a higher reduction (23%, 95% CI: 22, 24) than all other approaches. Although based on data from a single LTCF, when varying epidemiological parameters to extend to other pathogens, our results suggest that targeting supercontactors is always the most effective strategy, indicating this approach could be applied to prevent transmission of other nosocomial pathogens.</p><p><strong>Conclusions: </strong>By characterising the contact structure in hospital settings and identifying the categories of staff and patients more likely to be supercontactors, with either more or longer contacts than others, interventions against nosocomial spread could be more effective. We find that the most efficient implementation strategy depends on the intervention (reallocation, contact precautions, vaccination) and target population (staff, patients, supercontactors). Importantly, both staff and patients may be supercontactors, highlighting the importance of including patients in measures to prevent pathogen transmission in LTCF.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004433"},"PeriodicalIF":15.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856917","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 : 2024-07-25eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004437
Giles S H Yeo
In the Editorial, Giles Yeo discusses if it is possible that the UPF concept could be doing more harm than good.
在社论中,Giles Yeo 讨论了 UPF 概念是否可能弊大于利。
{"title":"Breaking our daily \"ultra-processed\" bread.","authors":"Giles S H Yeo","doi":"10.1371/journal.pmed.1004437","DOIUrl":"10.1371/journal.pmed.1004437","url":null,"abstract":"<p><p>In the Editorial, Giles Yeo discusses if it is possible that the UPF concept could be doing more harm than good.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004437"},"PeriodicalIF":15.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762038","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 : 2024-07-25eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004438
William Burman, Oxana Rucsineanu, C Robert Horsburgh, James Johnston, Susan E Dorman, Dick Menzies
In the Perspective, William Burman and colleagues advocate improving the safety and acceptability of treatment, rather than treatment-shortening, of rifampin-susceptible tuberculosis.
威廉-伯曼及其同事在《视角》中主张提高利福平易感结核病治疗的安全性和可接受性,而不是缩短治疗时间。
{"title":"Research on the treatment of rifampin-susceptible tuberculosis-Time for a new approach.","authors":"William Burman, Oxana Rucsineanu, C Robert Horsburgh, James Johnston, Susan E Dorman, Dick Menzies","doi":"10.1371/journal.pmed.1004438","DOIUrl":"10.1371/journal.pmed.1004438","url":null,"abstract":"<p><p>In the Perspective, William Burman and colleagues advocate improving the safety and acceptability of treatment, rather than treatment-shortening, of rifampin-susceptible tuberculosis.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004438"},"PeriodicalIF":15.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762039","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 : 2024-07-22eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004430
Sarah Cadot, Chloe Audebert, Charlotte Dion, Soleakhena Ken, Loic Dupré, Laetitia Largeaud, Camille Laurent, Loic Ysebaert, Fabien Crauste, Anne Quillet-Mary
<p><strong>Background: </strong>One of the first clinical observations of ibrutinib activity in the treatment of chronic lymphocytic leukemia (CLL) is a rapid decline in lymph nodes size. This phenomenon is accompanied by an hyperlymphocytosis, either transient or prolonged, which is associated with distinct clinical responses and thus has an impact on long-term outcomes. Understanding which factors determine distinct disease courses upon ibrutinib treatment remains a scientific challenge.</p><p><strong>Methods and findings: </strong>From 2016 to 2021, we conducted a longitudinal and observational study in 2 cohorts of patients with chronic lymphocytic leukemia (CLL) (cohort 1, n = 41; cohort 2, n = 81). These cohorts reflect the well-known clinical features of CLL patients, such as Male/Female sex ratio of 2/1, a median age of 70 years at diagnosis, and include patients in first-line therapy (27%) or relapsed/refractory patients (73%). Blood cell counts were followed for each patient during 2 years of ibrutinib treatment. In addition, immunophenotyping and whole-body magnetic resonance imaging (MRI) were assessed in patients from cohort 1. These data were integrated in a newly built mathematical model, inspired by previous mathematical works on CLL treatment and combining dynamical and statistical models, leading to the identification of biological mechanisms associated with the 2 types of clinical responses. This multidisciplinary approach allowed to identify baseline parameters that dictated lymphocytes kinetics upon ibrutinib treatment. Indeed, ibrutinib-induced lymphocytosis defined 2 CLL patient subgroups, transient hyperlymphocytosis (tHL) or prolonged hyperlymphocytosis (pHL), that can be discriminated, before the treatment, by absolute counts of CD4+ T lymphocytes (p = 0.026) and regulatory CD4 T cells (p = 0.007), programmed cell death protein 1 PD1 (p = 0.022) and CD69 (p = 0.03) expression on B leukemic cells, CD19/CD5high/CXCR4low level (p = 0.04), and lymph node cellularity. We also pinpointed that the group of patients identified by the transient hyperlymphocytosis has lower duration response and a poor clinical outcome. The mathematical approach led to the reproduction of patient-specific dynamics and the estimation of associated patient-specific biological parameters, and highlighted that the differences between the 2 groups were mainly due to the production of leukemic B cells in lymph node compartments, and to a lesser extent to T lymphocytes and leukemic B cell egress into bloodstream. Access to additional data, especially longitudinal MRI data, could strengthen the conclusions regarding leukemic B cell dynamics in lymph nodes and the relevance of 2 distinct groups of patients.</p><p><strong>Conclusions: </strong>Altogether, our multidisciplinary study provides a better understanding of ibrutinib response and highlights new pharmacodynamic parameters before and along ibrutinib treatment. Since our results highlight a reduced d
背景:伊布替尼治疗慢性淋巴细胞白血病(CLL)的首批临床观察结果之一是淋巴结体积迅速缩小。这一现象伴随着一过性或长期性的淋巴细胞增多,而淋巴细胞增多与不同的临床反应有关,因此会对长期预后产生影响。了解哪些因素决定了伊布替尼治疗后的不同病程仍是一项科学挑战:从2016年到2021年,我们对两组慢性淋巴细胞白血病(CLL)患者(组群1,n = 41;组群2,n = 81)进行了纵向观察研究。这些队列反映了CLL患者众所周知的临床特征,如男女性别比为2/1,诊断时的中位年龄为70岁,包括一线治疗患者(27%)或复发/难治患者(73%)。在伊布替尼治疗的两年期间,对每位患者的血细胞计数进行了跟踪。此外,还对第一组患者的免疫分型和全身磁共振成像(MRI)进行了评估。这些数据被整合到一个新建立的数学模型中,该数学模型的灵感来源于之前关于CLL治疗的数学研究,并结合了动态模型和统计模型,从而确定了与两种临床反应相关的生物机制。这种多学科方法有助于确定伊布替尼治疗时决定淋巴细胞动力学的基线参数。事实上,伊布替尼诱导的淋巴细胞增多定义了 2 个 CLL 患者亚群,即一过性淋巴细胞增多症(tHL)或长期淋巴细胞增多症(pHL),治疗前可通过 CD4+ T 淋巴细胞绝对计数(p = 0.026)和调节性 CD4 T 细胞(p = 0.007)、B 白血病细胞上程序性细胞死亡蛋白 1 PD1(p = 0.022)和 CD69(p = 0.03)的表达、CD19/CD5 高/CDXCR4 低水平(p = 0.04)和淋巴结细胞性。我们还发现,由一过性高淋巴细胞增多症识别出的一组患者的反应持续时间较短,临床预后较差。通过数学方法,我们再现了患者特异性的动态变化,并估算出了相关的患者特异性生物参数,突出表明两组患者之间的差异主要是由于淋巴结区白血病 B 细胞的产生,其次是 T 淋巴细胞和白血病 B 细胞进入血液。获得更多数据,尤其是纵向核磁共振成像数据,可以加强关于淋巴结中白血病B细胞动态以及两组不同患者相关性的结论:总之,我们的多学科研究让人们更好地了解了伊布替尼的反应,并强调了伊布替尼治疗前和治疗过程中的新药效学参数。由于我们的研究结果突显了一过性高淋巴细胞增多症患者的反应持续时间和结局缩短,因此我们的方法为伊布替尼治疗3个月后的管理提供了支持:试验注册:ClinicalTrials.gov NCT02824159。
{"title":"New pharmacodynamic parameters linked with ibrutinib responses in chronic lymphocytic leukemia: Prospective study in real-world patients and mathematical modeling.","authors":"Sarah Cadot, Chloe Audebert, Charlotte Dion, Soleakhena Ken, Loic Dupré, Laetitia Largeaud, Camille Laurent, Loic Ysebaert, Fabien Crauste, Anne Quillet-Mary","doi":"10.1371/journal.pmed.1004430","DOIUrl":"10.1371/journal.pmed.1004430","url":null,"abstract":"<p><strong>Background: </strong>One of the first clinical observations of ibrutinib activity in the treatment of chronic lymphocytic leukemia (CLL) is a rapid decline in lymph nodes size. This phenomenon is accompanied by an hyperlymphocytosis, either transient or prolonged, which is associated with distinct clinical responses and thus has an impact on long-term outcomes. Understanding which factors determine distinct disease courses upon ibrutinib treatment remains a scientific challenge.</p><p><strong>Methods and findings: </strong>From 2016 to 2021, we conducted a longitudinal and observational study in 2 cohorts of patients with chronic lymphocytic leukemia (CLL) (cohort 1, n = 41; cohort 2, n = 81). These cohorts reflect the well-known clinical features of CLL patients, such as Male/Female sex ratio of 2/1, a median age of 70 years at diagnosis, and include patients in first-line therapy (27%) or relapsed/refractory patients (73%). Blood cell counts were followed for each patient during 2 years of ibrutinib treatment. In addition, immunophenotyping and whole-body magnetic resonance imaging (MRI) were assessed in patients from cohort 1. These data were integrated in a newly built mathematical model, inspired by previous mathematical works on CLL treatment and combining dynamical and statistical models, leading to the identification of biological mechanisms associated with the 2 types of clinical responses. This multidisciplinary approach allowed to identify baseline parameters that dictated lymphocytes kinetics upon ibrutinib treatment. Indeed, ibrutinib-induced lymphocytosis defined 2 CLL patient subgroups, transient hyperlymphocytosis (tHL) or prolonged hyperlymphocytosis (pHL), that can be discriminated, before the treatment, by absolute counts of CD4+ T lymphocytes (p = 0.026) and regulatory CD4 T cells (p = 0.007), programmed cell death protein 1 PD1 (p = 0.022) and CD69 (p = 0.03) expression on B leukemic cells, CD19/CD5high/CXCR4low level (p = 0.04), and lymph node cellularity. We also pinpointed that the group of patients identified by the transient hyperlymphocytosis has lower duration response and a poor clinical outcome. The mathematical approach led to the reproduction of patient-specific dynamics and the estimation of associated patient-specific biological parameters, and highlighted that the differences between the 2 groups were mainly due to the production of leukemic B cells in lymph node compartments, and to a lesser extent to T lymphocytes and leukemic B cell egress into bloodstream. Access to additional data, especially longitudinal MRI data, could strengthen the conclusions regarding leukemic B cell dynamics in lymph nodes and the relevance of 2 distinct groups of patients.</p><p><strong>Conclusions: </strong>Altogether, our multidisciplinary study provides a better understanding of ibrutinib response and highlights new pharmacodynamic parameters before and along ibrutinib treatment. Since our results highlight a reduced d","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004430"},"PeriodicalIF":15.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749414","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 : 2024-07-18eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004429
Gabrielle Bonnet, John Bimba, Chancy Chavula, Harunavamwe N Chifamba, Titus H Divala, Andres G Lescano, Mohammed Majam, Danjuma Mbo, Auliya A Suwantika, Marco A Tovar, Pragya Yadav, Obinna Ekwunife, Collin Mangenah, Lucky G Ngwira, Elizabeth L Corbett, Mark Jit, Anna Vassall
Background: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice.
Methods and findings: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza.
Conclusions: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like
{"title":"Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.","authors":"Gabrielle Bonnet, John Bimba, Chancy Chavula, Harunavamwe N Chifamba, Titus H Divala, Andres G Lescano, Mohammed Majam, Danjuma Mbo, Auliya A Suwantika, Marco A Tovar, Pragya Yadav, Obinna Ekwunife, Collin Mangenah, Lucky G Ngwira, Elizabeth L Corbett, Mark Jit, Anna Vassall","doi":"10.1371/journal.pmed.1004429","DOIUrl":"10.1371/journal.pmed.1004429","url":null,"abstract":"<p><strong>Background: </strong>Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice.</p><p><strong>Methods and findings: </strong>We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza.</p><p><strong>Conclusions: </strong>COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004429"},"PeriodicalIF":15.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724821","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 : 2024-07-17eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004399
Ana Basto-Abreu, Rossana Torres-Alvarez, Tonatiuh Barrientos-Gutierrez, Paula Pereda, Ana Clara Duran
Background: The consumption of sugar-sweetened beverages (SSBs) is associated with obesity, metabolic diseases, and incremental healthcare costs. Given their health consequences, the World Health Organization (WHO) recommended that countries implement taxes on SSB. Over the last 10 years, obesity prevalence has almost doubled in Brazil, yet, in 2016, the Brazilian government cut the existing federal SSB taxes to their current 4%. Since 2022, a bill to impose a 20% tax on SSB has been under discussion in the Brazilian Senate. To simulate the potential impact of increasing taxes on SSB in Brazil, we aimed to estimate the price-elasticity of SSB and the potential impact of a new 20% or 30% excise SSB tax on consumption, obesity prevalence, and cost savings.
Methods and findings: Using household purchases data from the Brazilian Household Budget Survey (POF) from 2017/2018, we estimated constant elasticity regressions. We used a log-log specification by income level for all beverage categories: (1) sugar-sweetened beverages; (2) alcoholic beverages; (3) unsweetened beverages; and (4) low-calorie or artificially sweetened beverages. We estimated the adult nationwide baseline intake for each beverage category using 24-h dietary recall data collected in 2017/2018. Taking group one as the taxed beverages, we applied the price and cross-price elasticities to the baseline intake data, we obtained changes in caloric intake. The caloric reduction was introduced into an individual dynamic model to estimate changes in weight and obesity prevalence. No benefits on cost savings were modeled during the first 3 years of intervention to account for the time lag in obesity cases to reduce costs. We multiplied the reduction in obesity cases during 7 years by the obesity costs per capita to predict the costs savings attributable to the sweetened beverage tax. SSB price elasticities were higher among the lowest tertile of income (-1.24) than in the highest income tertile (-1.13), and cross-price elasticities suggest SSB were weakly substituted by milk, water, and 100% fruit juices. We estimated a caloric change of -17.3 kcal/day/person under a 20% excise tax and -25.9 kcal/day/person under a 30% tax. Ten years after implementation, a 20% tax is expected to reduce obesity prevalence by 6.7%; 9.1% for a 30% tax. These reductions translate into a -2.8 million and -3.8 million obesity cases for a 20% and 30% tax, respectively, and a reduction of $US 13.3 billion and $US 17.9 billion in obesity costs over 10 years for a 20% and 30% tax, respectively. Study limitations include using a quantile distribution method to adjust self-reported baseline weight and height, which could be insufficient to correct for reporting bias; also, weight, height, and physical activity were assumed to be steady over time.
Conclusions: Adding a 20% to 30% excise tax on top of Brazil's current federal tax could help to reduce the co
{"title":"Estimated reduction in obesity prevalence and costs of a 20% and 30% ad valorem excise tax to sugar-sweetened beverages in Brazil: A modeling study.","authors":"Ana Basto-Abreu, Rossana Torres-Alvarez, Tonatiuh Barrientos-Gutierrez, Paula Pereda, Ana Clara Duran","doi":"10.1371/journal.pmed.1004399","DOIUrl":"10.1371/journal.pmed.1004399","url":null,"abstract":"<p><strong>Background: </strong>The consumption of sugar-sweetened beverages (SSBs) is associated with obesity, metabolic diseases, and incremental healthcare costs. Given their health consequences, the World Health Organization (WHO) recommended that countries implement taxes on SSB. Over the last 10 years, obesity prevalence has almost doubled in Brazil, yet, in 2016, the Brazilian government cut the existing federal SSB taxes to their current 4%. Since 2022, a bill to impose a 20% tax on SSB has been under discussion in the Brazilian Senate. To simulate the potential impact of increasing taxes on SSB in Brazil, we aimed to estimate the price-elasticity of SSB and the potential impact of a new 20% or 30% excise SSB tax on consumption, obesity prevalence, and cost savings.</p><p><strong>Methods and findings: </strong>Using household purchases data from the Brazilian Household Budget Survey (POF) from 2017/2018, we estimated constant elasticity regressions. We used a log-log specification by income level for all beverage categories: (1) sugar-sweetened beverages; (2) alcoholic beverages; (3) unsweetened beverages; and (4) low-calorie or artificially sweetened beverages. We estimated the adult nationwide baseline intake for each beverage category using 24-h dietary recall data collected in 2017/2018. Taking group one as the taxed beverages, we applied the price and cross-price elasticities to the baseline intake data, we obtained changes in caloric intake. The caloric reduction was introduced into an individual dynamic model to estimate changes in weight and obesity prevalence. No benefits on cost savings were modeled during the first 3 years of intervention to account for the time lag in obesity cases to reduce costs. We multiplied the reduction in obesity cases during 7 years by the obesity costs per capita to predict the costs savings attributable to the sweetened beverage tax. SSB price elasticities were higher among the lowest tertile of income (-1.24) than in the highest income tertile (-1.13), and cross-price elasticities suggest SSB were weakly substituted by milk, water, and 100% fruit juices. We estimated a caloric change of -17.3 kcal/day/person under a 20% excise tax and -25.9 kcal/day/person under a 30% tax. Ten years after implementation, a 20% tax is expected to reduce obesity prevalence by 6.7%; 9.1% for a 30% tax. These reductions translate into a -2.8 million and -3.8 million obesity cases for a 20% and 30% tax, respectively, and a reduction of $US 13.3 billion and $US 17.9 billion in obesity costs over 10 years for a 20% and 30% tax, respectively. Study limitations include using a quantile distribution method to adjust self-reported baseline weight and height, which could be insufficient to correct for reporting bias; also, weight, height, and physical activity were assumed to be steady over time.</p><p><strong>Conclusions: </strong>Adding a 20% to 30% excise tax on top of Brazil's current federal tax could help to reduce the co","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004399"},"PeriodicalIF":15.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635166","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 : 2024-07-16eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004427
Natasha L Hezelgrave, Natalie Suff, Paul Seed, Vicky Robinson, Jenny Carter, Helena Watson, Alexandra Ridout, Anna L David, Susana Pereira, Fatemeh Hoveyda, Joanna Girling, Latha Vinayakarao, Rachel M Tribe, Andrew H Shennan
<p><strong>Background: </strong>Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy.</p><p><strong>Methods and findings: </strong>SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic.</p><p><strong>Conclusions: </strong>In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapi
{"title":"Comparing cervical cerclage, pessary and vaginal progesterone for prevention of preterm birth in women with a short cervix (SuPPoRT): A multicentre randomised controlled trial.","authors":"Natasha L Hezelgrave, Natalie Suff, Paul Seed, Vicky Robinson, Jenny Carter, Helena Watson, Alexandra Ridout, Anna L David, Susana Pereira, Fatemeh Hoveyda, Joanna Girling, Latha Vinayakarao, Rachel M Tribe, Andrew H Shennan","doi":"10.1371/journal.pmed.1004427","DOIUrl":"10.1371/journal.pmed.1004427","url":null,"abstract":"<p><strong>Background: </strong>Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT \"Stitch, Pessary, or Progesterone Randomised Trial\" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy.</p><p><strong>Methods and findings: </strong>SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic.</p><p><strong>Conclusions: </strong>In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapi","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004427"},"PeriodicalIF":15.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141628132","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 : 2024-07-15eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004422
Tomáš Formánek, Libor Potočár, Katrin Wolfova, Hana Melicharová, Karolína Mladá, Anna Wiedemann, Danni Chen, Pavel Mohr, Petr Winkler, Peter B Jones, Jiří Jarkovský
Background: Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities.
Methods and findings: We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals diagnosed with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people diagnosed with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mort
{"title":"Deaths with COVID-19 and from all-causes following first-ever SARS-CoV-2 infection in individuals with preexisting mental disorders: A national cohort study from Czechia.","authors":"Tomáš Formánek, Libor Potočár, Katrin Wolfova, Hana Melicharová, Karolína Mladá, Anna Wiedemann, Danni Chen, Pavel Mohr, Petr Winkler, Peter B Jones, Jiří Jarkovský","doi":"10.1371/journal.pmed.1004422","DOIUrl":"10.1371/journal.pmed.1004422","url":null,"abstract":"<p><strong>Background: </strong>Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities.</p><p><strong>Methods and findings: </strong>We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals diagnosed with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people diagnosed with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mort","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004422"},"PeriodicalIF":15.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621286","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 : 2024-07-11eCollection Date: 2024-07-01DOI: 10.1371/journal.pmed.1004302
Priscila F P S Pinto, James Macinko, Andréa F Silva, Iracema Lua, Gabriela Jesus, Laio Magno, Carlos A S Teles Santos, Maria Yury Ichihara, Mauricio L Barreto, Corrina Moucheraud, Luis E Souza, Inês Dourado, Davide Rasella
Background: Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality.
Methods and findings: A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study.
Conclusions: AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.
{"title":"The impact of primary health care on AIDS incidence and mortality: A cohort study of 3.4 million Brazilians.","authors":"Priscila F P S Pinto, James Macinko, Andréa F Silva, Iracema Lua, Gabriela Jesus, Laio Magno, Carlos A S Teles Santos, Maria Yury Ichihara, Mauricio L Barreto, Corrina Moucheraud, Luis E Souza, Inês Dourado, Davide Rasella","doi":"10.1371/journal.pmed.1004302","DOIUrl":"10.1371/journal.pmed.1004302","url":null,"abstract":"<p><strong>Background: </strong>Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality.</p><p><strong>Methods and findings: </strong>A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study.</p><p><strong>Conclusions: </strong>AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004302"},"PeriodicalIF":15.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591759","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}