PLoS Medicine最新文献

{"title":"Increasing coverage in cervical and colorectal cancer screening by leveraging attendance at breast cancer screening: A cluster-randomised, crossover trial.","authors":"Anne Dorte Lerche Helgestad, Mette Bach Larsen, Sisse Njor, Mette Tranberg, Lone Kjeld Petersen, Berit Andersen","doi":"10.1371/journal.pmed.1004431","DOIUrl":"10.1371/journal.pmed.1004431","url":null,"abstract":"<p><strong>Background: </strong>Screening participation remains suboptimal in cervical cancer (CC) and colorectal cancer (CRC) screening despite their effectiveness in reducing cancer-related morbidity and mortality. We investigated the effectiveness of an intervention by leveraging the high participation rate in breast cancer (BC) screening as an opportunity to offer self-sampling kits to nonparticipants in CC and CRC screening.</p><p><strong>Methods and findings: </strong>A pragmatic, unblinded, cluster-randomised, multiple period, crossover trial was conducted in 5 BC screening units in the Central Denmark Region (CDR) between September 1, 2021 and May 25, 2022. On each of 100 selected weekdays, 1 BC screening unit was randomly allocated as the intervention unit while the remaining units served as controls. Women aged 50 to 69 years attending BC screening at the intervention unit were offered administrative check-up on their CC screening status (ages 50 to 64 years) and CRC screening status (aged 50 to 69), and women with overdue screening were offered self-sampling. Women in the control group received only standard screening offers according to the organised programmes. The primary outcomes were differences between the intervention group and the control group in the total screening coverage for the 2 programmes and in screening participation among women with overdue screening, measured 6 months after the intervention. These were assessed using intention-to-treat analysis, reporting risk differences with 95% confidence intervals (CIs). A total of 27,116 women were included in the trial, with 5,618 (20.7%) in the intervention group and 21,498 (79.3%) in the control group. Six months after the intervention, total coverage was higher in the intervention group as compared with the control group in CC screening (88.3 versus 83.5, difference 4.8 percentage points, 95% CI [3.6, 6.0]; p < 0.001) and in CRC screening (79.8 versus 76.0, difference 3.8 percentage points, 95% CI [2.6, 5.1]; p < 0.001). Among women overdue with CC screening, participation in the intervention group was 32.0% compared with 6.1% in the control group (difference 25.8 percentage points, 95% CI [22.0, 29.6]; p < 0.001). In CRC screening, participation among women overdue with screening in the intervention group was 23.8% compared with 8.9% in the control group (difference 14.9 percentage points, 95% CI [12.3, 17.5]; p < 0.001). Women who did not participate in BC screening were not included in this study.</p><p><strong>Conclusions: </strong>Offering self-sampling to women overdue with CC and CRC screening when they attend BC screening was a feasible intervention, resulting in an increase in participation and total coverage. Other interventions are required to reach women who are not participating in BC screening.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05022511. The record of processing activities for research projects in the Central Denmark Region (R. N","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004431"},"PeriodicalIF":15.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977012","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}

{"title":"Equity considerations in clinical practice guidelines for traumatic brain injury and the criminal justice system: A systematic review.","authors":"Zoe Colclough, Maria Jennifer Estrella, Julie Michele Joyce, Sara Hanafy, Jessica Babineau, Angela Colantonio, Vincy Chan","doi":"10.1371/journal.pmed.1004418","DOIUrl":"10.1371/journal.pmed.1004418","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is disproportionately prevalent among individuals who intersect or are involved with the criminal justice system (CJS). In the absence of appropriate care, TBI-related impairments, intersecting social determinants of health, and the lack of TBI awareness in CJS settings can lead to lengthened sentences, serious disciplinary charges, and recidivism. However, evidence suggests that most clinical practice guidelines (CPGs) overlook equity and consequently, the needs of disadvantaged groups. As such, this review addressed the research question \"To what extent are (1) intersections with the CJS considered in CPGs for TBI, (2) TBI considered in CPGs for CJS, and (3) equity considered in CPGs for CJS?\".</p><p><strong>Methods and findings: </strong>CPGs were identified from electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), targeted websites, Google Search, and reference lists of identified CPGs on November 2021 and March 2023 (CPGs for TBI) and May 2022 and March 2023 (CPGs for CJS). Only CPGs for TBI or CPGs for CJS were included. We calculated the proportion of CPGs that included TBI- or CJS-specific content, conducted a qualitative content analysis to understand how evidence regarding TBI and the CJS was integrated in the CPGs, and utilised equity assessment tools to understand if and how equity was considered. Fifty-seven CPGs for TBI and 6 CPGs for CJS were included in this review. Fourteen CPGs for TBI included information relevant to the CJS, but only 1 made a concrete recommendation to consider legal implications during vocational evaluation in the forensic context. Two CPGs for CJS acknowledged the prevalence of TBI among individuals in prison and one specifically recommended considering TBI during health assessments. Both CPGs for TBI and CPGs for CJS provided evidence specific to a single facet of the CJS, predominantly in policing and corrections. The use of equity best practices and the involvement of disadvantaged groups in the development process were lacking among CPGs for CJS. We acknowledge limitations of the review, including that our searches were conducted in English language and thus, we may have missed other non-English language CPGs in this review. We further recognise that we are unable to comment on evidence that is not integrated in the CPGs, as we did not systematically search for research on individuals with TBI who intersect with the CJS, outside of CPGs.</p><p><strong>Conclusions: </strong>Findings from this review provide the foundation to consider CJS involvement in CPGs for TBI and to advance equity in CPGs for CJS. Conducting research, including investigating the process of screening for TBI with individuals who intersect with all facets of the CJS, and utilizing equity assessment tools in guideline development are critical steps to enhance equity in healthcare for this disadvantaged group.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004418"},"PeriodicalIF":15.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972171","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}

{"title":"Primary care to further improve vertical HIV programming outcomes: From spillover to strategy.","authors":"Elvin H Geng, Ana Mocumbi, Wilbroad Mutale, Victor Davila-Roman, Michael Reid","doi":"10.1371/journal.pmed.1004434","DOIUrl":"10.1371/journal.pmed.1004434","url":null,"abstract":"","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004434"},"PeriodicalIF":15.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894709","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}

{"title":"Benefits of specialist palliative care by identifying active ingredients of service composition, structure, and delivery model: A systematic review with meta-analysis and meta-regression.","authors":"Miriam J Johnson, Leah Rutterford, Anisha Sunny, Sophie Pask, Susanne de Wolf-Linder, Fliss E M Murtagh, Christina Ramsenthaler","doi":"10.1371/journal.pmed.1004436","DOIUrl":"10.1371/journal.pmed.1004436","url":null,"abstract":"<p><strong>Background: </strong>Specialist palliative care (SPC) services address the needs of people with advanced illness. Meta-analyses to date have been challenged by heterogeneity in SPC service models and outcome measures and have failed to produce an overall effect. The best service models are unknown. We aimed to estimate the summary effect of SPC across settings on quality of life and emotional wellbeing and identify the optimum service delivery model.</p><p><strong>Methods and findings: </strong>We conducted a systematic review with meta-analysis and meta-regression. Databases (Cochrane, MEDLINE, CINAHL, ICTRP, clinicaltrials.gov) were searched (January 1, 2000; December 28, 2023), supplemented with further hand searches (i.e., conference abstracts). Two researchers independently screened identified studies. We included randomized controlled trials (RCTs) testing SPC intervention versus usual care in adults with life-limiting disease and including patient or proxy reported outcomes as primary or secondary endpoints. The meta-analysis used, to our knowledge, novel methodology to convert outcomes into minimally clinically important difference (MID) units and the number needed to treat (NNT). Bias/quality was assessed via the Cochrane Risk of Bias 2 tool and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Random-effects meta-analyses and meta-regressions were used to synthesize endpoints between 2 weeks and 12 months for effect on quality of life and emotional wellbeing expressed and combined in units of MID. From 42,787 records, 39 international RCTs (n = 38 from high- and middle-income countries) were included. For quality of life (33 trials) and emotional wellbeing (22 trials), statistically and clinically significant benefit was seen from 3 months' follow-up for quality of life, standardized mean difference (SMD in MID units) effect size of 0.40 at 13 to 36 weeks, 95% confidence interval (CI) [0.21, 0.59], p < 0.001, I2 = 60%). For quality of life at 13 to 36 weeks, 13% of the SPC intervention group experienced an effect of at least 1 MID unit change (relative risk (RR) = 1.13, 95% CI [1.06, 1.20], p < 0.001, I2 = 0%). For emotional wellbeing, 16% experienced an effect of at least 1 MID unit change at 13 to 36 weeks (95% CI [1.08, 1.24], p < 0.001, I2 = 0%). For quality of life, the NNT improved from 69 to 15; for emotional wellbeing from 46 to 28, from 2 weeks and 3 months, respectively. Higher effect sizes were associated with multidisciplinary and multicomponent interventions, across settings. Sensitivity analyses using robust MID estimates showed substantial (quality of life) and moderate (emotional wellbeing) benefits, and lower number-needed-to-treat, even with shorter follow-up. As the main limitation, MID effect sizes may be biased by relying on derivation in non-palliative care samples.</p><p><strong>Conclusions: </strong>Using, to our knowledge, nove","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004436"},"PeriodicalIF":15.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879725","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}

{"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}

{"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}

{"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}

{"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}

{"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;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}

{"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}