PLoS Medicine最新文献

{"title":"Medical imaging utilization in migrants compared with nonmigrants in a universal healthcare system: A population-based matched cohort study.","authors":"Giancarlo Di Giuseppe, Rinku Sutradhar, Priscila Pequeno, Marilyn L Kwan, Diana L Miglioretti, Rebecca Smith-Bindman, Jason D Pole","doi":"10.1371/journal.pmed.1004474","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004474","url":null,"abstract":"<p><strong>Background: </strong>Medical imaging is an integral part of healthcare. Globalization has resulted in increased mobilization of migrants to new host nations. The association between migration status and utilization of medical imaging is unknown.</p><p><strong>Methods and findings: </strong>A retrospective population-based matched cohort study was conducted in Ontario, Canada from April 1, 1995 to December 31, 2016. A total of 1,848,222 migrants were matched 1:1 to nonmigrants in the year of migration on age, sex, and geography. Utilization of computed tomography (CT), magnetic resonance imaging (MRI), radiography, and ultrasonography was determined. Rate differences per 1,000 person-years comparing migrants to nonmigrants were calculated. Relative rates were calculated using a recurrent event framework, adjusting for age, sex, and time-varying socioeconomic status, comorbidity score, and access to a primary care provider. Estimates were stratified by migration age: children and adolescents (≤19 years), young adults (20 to 39), adults (40 to 59), and older adults (≥60). Utilization rates of CT, MRI, and radiography were lower for migrants across all age groups compared with Ontario nonmigrants. Increasing age at migration was associated with larger differences in utilization rates. Older adult migrants had the largest gap in imaging utilization. The longer the time since migration, the larger the gap in medical imaging use. In multivariable analysis, the relative rate of imaging was approximately 20% to 30% lower for migrants: ranging from 0.77 to 0.88 for CT and 0.72 to 0.80 for MRI imaging across age groups. Radiography relative rates ranged from 0.84 to 0.90. All migrant age groups, except older adults, had higher rates of ultrasonography. The indication for imaging was not captured, thus it was not possible to determine if the imaging was necessary.</p><p><strong>Conclusions: </strong>Migrants utilized less CT, MRI, and radiography but more ultrasonography. Older adult migrants used the least amount of imaging compared with nonmigrants. Future research should evaluate whether lower utilization is due to barriers in healthcare access or health-seeking behaviors within a universal healthcare system.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004474"},"PeriodicalIF":15.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511178","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":"Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands.","authors":"Bouke Catherine de Jong, Said Nourdine, Auke Thomas Bergeman, Zahara Salim, Silahi Halifa Grillone, Sofie Marijke Braet, Mohamed Wirdane Abdou, Rian Snijders, Maya Ronse, Carolien Hoof, Achilleas Tsoumanis, Nimer Ortuño-Gutiérrez, Christian van der Werf, Alberto Piubello, Aboubacar Mzembaba, Younoussa Assoumani, Epco Hasker","doi":"10.1371/journal.pmed.1004453","DOIUrl":"10.1371/journal.pmed.1004453","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) &lt;450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a &lt;10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI -1.8, 5.3, p = 0.41). No individual's QTc increased by &gt;50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampici","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004453"},"PeriodicalIF":15.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478608","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":"Risk of common psychiatric disorders, suicidal behaviours, and premature mortality following violent victimisation: A matched cohort and sibling-comparison study of 127,628 people who experienced violence in Finland and Sweden.","authors":"Amir Sariaslan, Joonas Pitkänen, Jonas Forsman, Ralf Kuja-Halkola, Isabell Brikell, Brian M D'Onofrio, Mikko Aaltonen, Henrik Larsson, Pekka Martikainen, Paul Lichtenstein, Seena Fazel","doi":"10.1371/journal.pmed.1004410","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004410","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Associations between violent victimisation and psychiatric disorders are hypothesised to be bidirectional, but the role of violent victimisation in the aetiologies of psychiatric disorders and other adverse outcomes remains unclear. We aimed to estimate associations between violent victimisation and subsequent common psychiatric disorders, suicidal behaviours, and premature mortality while accounting for unmeasured familial confounders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Using nationwide registers, we identified a total of 127,628 individuals born in Finland (1987 to 2004) and Sweden (1973 to 2004) who had experienced violent victimisation, defined as either hospital admissions or secondary care outpatient visits for assault-related injuries. These were age- and sex-matched with up to 10 individuals in the general population (n = 1,276,215). Additionally, we matched those who had experienced violent victimisation with their unaffected siblings (n = 132,408). Outcomes included depression, anxiety, personality disorders, alcohol use disorders, drug use disorders, suicidal behaviours, and premature mortality. Participants were followed from the victimisation date until the date of the outcome, emigration, death, or December 31, 2020, whichever occurred first. Country-specific associations were estimated using stratified Cox regression models, which also accounted for unmeasured familial confounders via sibling comparisons. The country-specific associations were then pooled using meta-analytic models. Among 127,628 patients (69.0% male) who had experienced violent victimisation, the median age at first violent victimisation was 21 (interquartile range: 18 to 26) years. Incidence of all outcomes was larger in those who were exposed to violent victimisation compared to population controls, ranging from 2.3 (95% confidence interval (CI) [2.2; 2.4]) per 1,000 person-years for premature mortality (compared with 0.6, 95% CI [0.6; 0.6], in controls) to 22.5 (95% CI [22.3; 22.8]) per 1,000 person-years for anxiety (compared with 7.3, 95% CI [7.3; 7.4], in controls). In adjusted models, people who had experienced violent victimisation were between 2 to 3 times as likely as their siblings to develop any of the outcomes, ranging from adjusted hazard ratio [aHR] 1.7 (95% CI [1.7; 1.8]) for depression to 3.0 (95% CI [2.9; 3.1]) for drug use disorders. Risks remained elevated 2 years post-victimisation, ranging from aHR 1.4 (95% CI [1.3; 1.5]) for depression to 2.3 (95% CI [2.2; 2.4]) for drug use disorders. Our reliance on secondary care data likely excluded individuals with milder assault-related injuries and less severe psychiatric symptoms, thus suggesting that our estimates may be conservative. Another limitation is the possibility of residual genetic confounding, as full siblings share on average about half of their co-segregating genes. However, the associations remained robust even after adjusting for both measured","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004410"},"PeriodicalIF":15.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478555","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":"Manufactured meals: The challenges of ultraprocessed foods.","authors":"Alexandra Tosun","doi":"10.1371/journal.pmed.1004477","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004477","url":null,"abstract":"<p><p>In this Editorial on behalf of the PLOS Medicine Editors, Alexandra Tosun discusses how ultra-processed food has found itself at the center of a growing storm of criticism, the complexities of the ongoing nutrition debate and why stakeholders must be held to higher standards.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004477"},"PeriodicalIF":15.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478554","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":"Ultraprocessed food (UPF), health, and mechanistic uncertainty: What should we be advising the public to do about UPFs?","authors":"Eric Robinson, Alexandra M Johnstone","doi":"10.1371/journal.pmed.1004439","DOIUrl":"10.1371/journal.pmed.1004439","url":null,"abstract":"<p><p>In this perspective, we discuss why current mechanistic uncertainty on ultraprocessed foods (UPFs) and health acts as a major challenge to providing informed dietary guidelines and public advice on UPFs. Based on the balance of current evidence, we do not believe it is appropriate to be advising consumers to avoid all UPFs and we await further evidence to inform consumer guidance on the need to limit consumption of specifics foods based on their degree or type of processing.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004439"},"PeriodicalIF":15.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478609","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":"Growth, physical, and cognitive function in children who are born HIV-free: School-age follow-up of a cluster-randomised trial in rural Zimbabwe.","authors":"Joe D Piper, Clever Mazhanga, Marian Mwapaura, Gloria Mapako, Idah Mapurisa, Tsitsi Mashedze, Eunice Munyama, Maria Kuona, Thombizodwa Mashiri, Kundai Sibanda, Dzidzai Matemavi, Monica Tichagwa, Soneni Nyoni, Asinje Saidi, Manasa Mangwende, Dzivaidzo Chidhanguro, Eddington Mpofu, Joice Tome, Gabriel Mbewe, Batsirai Mutasa, Bernard Chasekwa, Handrea Njovo, Chandiwana Nyachowe, Mary Muchekeza, Kuda Mutasa, Virginia Sauramba, Ceri Evans, Melissa J Gladstone, Jonathan C Wells, Elizabeth Allen, Melanie Smuk, Jean H Humphrey, Lisa F Langhaug, Naume V Tavengwa, Robert Ntozini, Andrew J Prendergast","doi":"10.1371/journal.pmed.1004347","DOIUrl":"10.1371/journal.pmed.1004347","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood by 2022. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterised school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;The SHINE trial enrolled pregnant women between 2012 and 2015 across 2 rural Zimbabwean districts. Co-primary outcomes were height-for-age Z-score and haemoglobin at age 18 months (clinicaltrials.gov NCT01824940). Children were re-enrolled if they were aged 7 years, resident in Shurugwi district, and had known pregnancy HIV-exposure status. From 5,280 pregnant women originally enrolled, 376 CBHF and 2016 CHU reached the trial endpoint at 18 months in Shurugwi; of these, 264 CBHF and 990 CHU were evaluated at age 7 years using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox. Cognitive function was evaluated using the Kaufman Assessment Battery for Children (KABC-II), with additional tools measuring executive function, literacy, numeracy, fine motor skills, and socioemotional function. Physical function was assessed using standing broad jump and handgrip for strength, and the shuttle-run test for cardiovascular fitness. Growth was assessed by anthropometry. Body composition was assessed by bioimpedance analysis and skinfold thicknesses. A caregiver questionnaire measured demographics, socioeconomic status, nurturing, child discipline, food, and water insecurity. We prespecified the primary comparisons and used generalised estimating equations with an exchangeable working correlation structure to account for clustering. Adjusted models used covariates from the trial (study arm, study nurse, exact child age, sex, calendar month measured, and ambient temperature). They also included covariates derived from directed acyclic graphs, with separate models adjusted for contemporary variables (socioeconomic status, household food insecurity, religion, social support, gender norms, caregiver depression, age, caregiver education, adversity score, and number of children's books) and early-life variables (length-for-age-Z-score) at 18 months, birthweight, maternal baseline depression, household diet, maternal schooling and haemoglobin, socioeconomic status, facility birth, and gender norms. We applied a Bonferroni correction for the 27 comparisons (0.05/27) with threshold of p &lt; 0.00185 as significant. We found strong evidence that cognitive function was lower in CBHF compared to CHU across multiple domains. The KABC-II mental processing index was 45.2 (standard deviation (SD) 10.5) in CBHF and 48.3 (11.3) in CHU (mean differ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004347"},"PeriodicalIF":15.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407087","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 a patient-reported outcome-based remote monitoring and alert intervention for early detection of critical recovery after joint replacement: A randomised controlled trial.","authors":"Lukas Schöner, David Kuklinski, Laura Wittich, Viktoria Steinbeck, Benedikt Langenberger, Thorben Breitkreuz, Felix Compes, Mathias Kretzler, Ursula Marschall, Wolfgang Klauser, Mustafa Citak, Georg Matziolis, Daniel Schrednitzki, Kim Grasböck, Justus Vogel, Christoph Pross, Reinhard Busse, Alexander Geissler","doi":"10.1371/journal.pmed.1004459","DOIUrl":"10.1371/journal.pmed.1004459","url":null,"abstract":"<p><strong>Background: </strong>While the effectiveness of patient-reported outcome measures (PROMs) as an intervention to impact patient pathways has been established for cancer care, it is unknown for other indications. We assessed the cost-effectiveness of a PROM-based monitoring and alert intervention for early detection of critical recovery paths following hip and knee replacement.</p><p><strong>Methods and findings: </strong>The cost-effectiveness analysis (CEA) is based on a multicentre randomised controlled trial encompassing 3,697 patients with hip replacement and 3,110 patients with knee replacement enrolled from 2019 to 2020 in 9 German hospitals. The analysis was conducted with a subset of 546 hip and 492 knee replacement cases with longitudinal cost data from 24 statutory health insurances. Patients were randomised 1:1 to a PROM-based remote monitoring and alert intervention or to a standard care group. All patients were assessed at 12-months post-surgery via digitally collected PROMs. Patients within the intervention group were additionally assessed at 1-, 3-, and 6-months post-surgery to be contacted in case of critical recovery paths. For the effect evaluation, a PROM-based composite measure (PRO-CM) was developed, combining changes across various PROMs in a single index ranging from 0 to 100. The PRO-CM included 6 PROMs focused on quality of life and various aspects of physical and mental health. The primary outcome was the incremental cost-effectiveness ratio (ICER). The intervention group showed incremental outcomes of 2.54 units PRO-CM (95% confidence interval (CI) [0.93, 4.14]; p = 0.002) for patients with hip and 0.87 (95% CI [-0.94, 2.67]; p = 0.347) for patients with knee replacement. Within the 12-months post-surgery period the intervention group had less costs of 376.43€ (95% CI [-639.74, -113.12]; p = 0.005) in patients with hip, and 375.50€ (95% CI [-767.40, 16.39]; p = 0.060) in patients with knee replacement, revealing a dominant ICER for both procedures. However, it remains unclear which step of the multistage intervention contributes most to the positive effect.</p><p><strong>Conclusions: </strong>The intervention significantly improved patient outcomes at lower costs in patients with hip replacements when compared with standard care. Further it showed a nonsignificant cost reduction in knee replacement patients. This reinforces the notion that PROMs can be utilised as a cost-effective instrument for remote monitoring in standard care settings.</p><p><strong>Trial registration: </strong>Registration: German Register for Clinical Studies (DRKS) under DRKS00019916.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004459"},"PeriodicalIF":15.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394577","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":"Estimating the risk and spatial spread of measles in populations with high MMR uptake: Using school-household networks to understand the 2013 to 2014 outbreak in the Netherlands.","authors":"James D Munday, Katherine E Atkins, Don Klinkenberg, Marc Meurs, Erik Fleur, Susan Jm Hahné, Jacco Wallinga, Albert Jan van Hoek","doi":"10.1371/journal.pmed.1004466","DOIUrl":"10.1371/journal.pmed.1004466","url":null,"abstract":"<p><strong>Background: </strong>Measles outbreaks are still routine, even in countries where vaccination coverage exceeds the guideline of 95%. Therefore, achieving ambitions for measles eradication will require understanding of how unvaccinated children interact with others who are unvaccinated. It is well established that schools and homes are key settings for both clustering of unvaccinated children and for transmission of infection. In this study, we evaluate the potential for contacts between unvaccinated children in these contexts to facilitate measles outbreaks with a focus on the Netherlands, where large outbreaks have been observed periodically since the introduction of mumps, measles and rubella (MMR).</p><p><strong>Methods and findings: </strong>We created a network of all primary and secondary schools in the Netherlands based on the total number of household pairs between each school. A household pair are siblings from the same household who attend a different school. We parameterised the network with individual level administrative school and household data provided by the Dutch Ministry for Education and estimates of school level uptake of the MMR vaccine. We analysed the network to establish the relative strength of contact between schools and found that schools associated with low vaccine uptake are highly connected, aided by a differentiated school system in the Netherlands (Coleman homophily index (CHI) = 0.63). We simulated measles outbreaks on the network and evaluated the model against empirical measles data per postcode area from a large outbreak in 2013 (2,766 cases). We found that the network-based model could reproduce the observed size and spatial distribution of the historic outbreak much more clearly than the alternative models, with a case weighted receiver operating characteristic (ROC) sensitivity of 0.94, compared to 0.17 and 0.26 for models that do not account for specific network structure or school-level vaccine uptake, respectively. The key limitation of our framework is that it neglects transmission routes outside of school and household contexts.</p><p><strong>Conclusions: </strong>Our framework indicates that clustering of unvaccinated children in primary schools connected by unvaccinated children in related secondary schools lead to large, connected clusters of unvaccinated children. Using our approach, we could explain historical outbreaks on a spatial level. Our framework could be further developed to aid future outbreak response.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004466"},"PeriodicalIF":15.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394578","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":"The incidence of postoperative periprosthetic femoral fracture following total hip replacement: An analysis of UK National Joint Registry and Hospital Episodes statistics data.","authors":"Jonathan Nicholas Lamb, Jonathan Thomas Evans, Samuel Relton, Michael Richard Whitehouse, J Mark Wilkinson, Hemant Pandit","doi":"10.1371/journal.pmed.1004462","DOIUrl":"10.1371/journal.pmed.1004462","url":null,"abstract":"<p><strong>Background: </strong>Postoperative periprosthetic femoral fracture (POPFF) after total hip replacement (THR) requires complex surgery and is associated with a high morbidity, mortality, and cost. Although the United Kingdom based National Joint Registry (NJR) captures over 95% of THRs treated with revision, before June 2023 it did not capture POPFF treated with fixation. We aimed to estimate the incidence and epidemiology of POPFF treated with either surgery in England.</p><p><strong>Methods and findings: </strong>We performed a retrospective analysis of a mandatory, prospective database (NJR) linked to Hospital Episode Statistics (HES). All linkable primary THRs between 01/01/2004 and 31/12/2020 were included. Revision or fixation of POPFF were identified using a combination of procedural and diagnosis codes. We identified 809,832 THRs representing 5,542,332 prosthesis years at risk. A total of 5,100 POPFF were identified that had been surgically treated by revision, fixation, or both, and 2,831 of these fractures were treated with fixation alone, meaning 56% were not represented with revision data alone. The incidence of POPFF needing surgery was 0.92 (95% CI 0.90, 0.95) per 1,000 prostheses years. This incidence was higher in patients over the age of 70 at the time of primary THR (1.31 [95% CI 1.26, 1.35] per 1,000 prostheses years) and for patients who underwent THR for hip fracture (2.19 [95% CI 1.97, 2.42] per 1,000 prostheses years). This incidence appears to be increasing year on year. The cumulative probability of sustaining a POPFF within 10 years of THR was 1% and over 15% of patients died within 1 year of surgery for a POPFF.</p><p><strong>Conclusions: </strong>To date, the incidence of POPFF may have been underestimated with over 50% of cases missed if the case identification in this study is correct. After including these cases, we observed that POPFF is the largest reason for major reoperation following THR and patients sustaining these injuries have a high risk of death. The prevention and treatment of POPFF and requires further resource allocation and research.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 10","pages":"e1004462"},"PeriodicalIF":15.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367057","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":"Methaemoglobin as a surrogate marker of primaquine antihypnozoite activity in Plasmodium vivax malaria: A systematic review and individual patient data meta-analysis.","authors":"Ihsan Fadilah, Robert J Commons, Nguyen Hoang Chau, Cindy S Chu, Nicholas P J Day, Gavin C K W Koh, Justin A Green, Marcus Vg Lacerda, Alejandro Llanos-Cuentas, Erni J Nelwan, Francois Nosten, Ayodhia Pitaloka Pasaribu, Inge Sutanto, Walter R J Taylor, Kamala Thriemer, Ric N Price, Nicholas J White, J Kevin Baird, James A Watson","doi":"10.1371/journal.pmed.1004411","DOIUrl":"10.1371/journal.pmed.1004411","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The 8-aminoquinolines, primaquine and tafenoquine, are the only available drugs for the radical cure of Plasmodium vivax hypnozoites. Previous evidence suggests that there is dose-dependent 8-aminoquinoline induced methaemoglobinaemia and that higher methaemoglobin concentrations are associated with a lower risk of P. vivax recurrence. We undertook a systematic review and individual patient data meta-analysis to examine the utility of methaemoglobin as a population-level surrogate endpoint for 8-aminoquinoline antihypnozoite activity to prevent P. vivax recurrence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We conducted a systematic search of Medline, Embase, Web of Science, and the Cochrane Library, from 1 January 2000 to 29 September 2022, inclusive, of prospective clinical efficacy studies of acute, uncomplicated P. vivax malaria mono-infections treated with radical curative doses of primaquine. The day 7 methaemoglobin concentration was the primary surrogate outcome of interest. The primary clinical outcome was the time to first P. vivax recurrence between day 7 and day 120 after enrolment. We used multivariable Cox proportional-hazards regression with site random-effects to characterise the time to first recurrence as a function of the day 7 methaemoglobin percentage (log base 2 transformed), adjusted for the partner schizonticidal drug, the primaquine regimen duration as a proxy for the total primaquine dose (mg base/kg), the daily primaquine dose (mg/kg), and other factors. The systematic review protocol was registered with PROSPERO (CRD42023345956). We identified 219 P. vivax efficacy studies, of which 8 provided relevant individual-level data from patients treated with primaquine; all were randomised, parallel arm clinical trials assessed as having low or moderate risk of bias. In the primary analysis data set, there were 1,747 patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity enrolled from 24 study sites across 8 different countries (Indonesia, Brazil, Vietnam, Thailand, Peru, Colombia, Ethiopia, and India). We observed an increasing dose-response relationship between the daily weight-adjusted primaquine dose and day 7 methaemoglobin level. For a given primaquine dose regimen, an observed doubling in day 7 methaemoglobin percentage was associated with an estimated 30% reduction in the risk of P. vivax recurrence (adjusted hazard ratio = 0.70; 95% confidence interval [CI] [0.57, 0.86]; p = 0.0005). These pooled estimates were largely consistent across the study sites. Using day 7 methaemoglobin as a surrogate endpoint for recurrence would reduce required sample sizes by approximately 40%. Study limitations include the inability to distinguish between recrudescence, reinfection, and relapse in P. vivax recurrences.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;For a given primaquine regimen, higher methaemoglobin on day 7 was associated with a reduced risk of P. vivax recurrence. Under our prop","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004411"},"PeriodicalIF":15.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330665","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}