Open Forum Infectious Diseases
◐ Oxford University Press (OUP)
Preprints posted in the last 90 days, ranked by how well they match Open Forum Infectious Diseases's content profile, based on 134 papers previously published here. The average preprint has a 0.08% match score for this journal, so anything above that is already an above-average fit.
Preiksaitis, C. M.; Hughes, J.; Iscoe, M.; Makutonin, M.; Rider, A.; Melnick, E.; Rose, C.
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Objectives: Electronic Health Records (EHRs) impose a significant time burden on physicians, often requiring work to be completed outside of scheduled hours. While this burden is well-documented, how it evolves throughout emergency medicine (EM) residency remains poorly understood. This study aimed to quantify EHR usage patterns, analyze the composition of after-shift work, and characterize the development of EHR efficiency across EM training. Methods: We conducted a retrospective cohort study of EM residents (postgraduate year [PGY] 1-4) using 5.5 years of EHR audit log data (2020-2025) at a single academic institution. We analyzed EHR time per new patient encounter, stratified by postgraduate year, and categorized activities into domains such as documentation, chart review, and orders. EHR work was measured both during and after scheduled shifts. Results: The analysis included 144 unique residents and 167,010 new patient encounters across 15,386 shifts. Encounter-attributed EHR time per encounter decreased by 52% from PGY-1 to PGY-4 (median 19.9 to 9.6 minutes, p<0.001), despite an 86% increase in patient volume per shift (median 7 to 13 encounters). This efficiency gain was driven primarily by a 69% reduction in documentation time (9.3 to 2.9 minutes), accompanied by shorter notes. After-shift work (EHR activity after the 9-hour clinical shift) was present in 89.9-94.4% of encounters. At the shift level, combined after-shift EHR time (encounter-attributed plus tracking board) was a median of 64.2 minutes per shift for PGY-1 and 104.2 minutes for PGY-4. Shift-level tracking board activity dominated the after-shift burden and increased with training (median 40.2 to 79.0 minutes per shift from PGY-1 to PGY-4). Conclusions: EM residents achieve substantial gains in on-shift EHR efficiency, with the largest reductions observed in documentation time, accompanied by shorter notes and faster input speed. However, a persistent after-hours workload, dominated by administrative and patient flow tasks, suggests that (at least at this single institution) system-level factors--not just individual skill--may contribute to this pattern. Monitoring these objective EHR metrics may help programs identify struggling learners and evaluate the impact of interventions aimed at improving resident well-being and workflow efficiency.
Nakiyingi, L.; Kikaire, B.; Nakayenga, S.; Kamulegeya, L.; Nakabugo, E.; Asio, J. N.; Bagaya, B.; Ssengooba, W.; Mayanja-Kizza, H.; Manabe, Y. C.
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Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population where the majority are or have been on antiretroviral therapy (ART), comparing mortality between those who received empiric TB treatment and those who did not. Materials and Methods: From November 2017 to December 2020, Xpert-negative presumptive TB adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29-45) years, 82.3% on ART, median CD4 206 cells/mm3 (IQR 36-507). Of the 300 participants, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 91.4% among inpatients, 72% within three months post-enrolment. Mortality was higher among those who received empiric TB treatment (51.5 vs. 30.2 per 1,000 person-months; p=0.013) compared to those who did not. TB cultures were positive in 5.0% (15/300), of whom seven (46.7%) were also TB-LAM positive. CrAg was positive in 12.3% and 3.7% had positive blood culture. Conclusion: We found high mortality among Xpert-negative PLHIV, particularly those who received empiric TB treatment, despite high ART coverage. Cryptococcal antigenemia and bacteremia were not uncommon. In presence of negative Xpert results in PLHIV, clinicians should perform extensive laboratory evaluations to identify possible comorbidities or alternative non-TB diagnosis.
Bianchina, N.; Fischer, C.; Rai, K.; Clawson, J.; McBeth, L.; Gottenborg, E.; Keniston, A.; Burden, M.
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BackgroundHigh workload among healthcare workers has increasingly been correlated with poor patient outcomes, inefficient operational and financial outcomes, and burnout. Despite growing literature exploring causes of attending physician workload, there is limited understanding of trainee-specific measures. ObjectiveWe aimed to characterize elements contributing to trainee workload and perceived challenges and satisfiers to the trainee workday as a foundation for better understanding and measuring trainee work experience. MethodsInternal Medicine and Medicine-Pediatrics residents at an academic medical center were invited to participate in focus groups discussing contributors to inpatient workload and work experience between March and April 2024. A qualitative content analysis identified key metrics of trainee workload and work experience, which were then consolidated into overarching domains. A structured, multi-round rating process ranked the perceived relevance of each metric. ResultsTwenty residents participated across six focus groups. Analysis of focus groups yielded 297 workload metrics across 28 unique domains. Seventeen domains had metrics identified as highly relevant (median 6-7; IQR < 1) including autonomy, communication, disruptions, task switching, documentation, emotional burden, patient factors, professional fulfillment, rounding, teaming, and work-life balance. ConclusionsResident physicians highlighted complex interactions between clinical factors, work design, and psychosocial dynamics that contribute to their sense of workload. This creates opportunities to develop unique measures of workload to understand the trainee experience better. Further studies are needed to capture the generalizability of these findings and the relationship between these workload domains and patient, organizational, and trainee outcomes with the aim of implementing evidence-based work design.
McNair, E. A.; Kwon, J. H.; Grijalva, C. G.; McLaren, S. H.; Biddle, J. E.; Dean, S.; White, E. B.; Fritz, S. A.; Presti, R. M.; O'Neil, C. A.; Sano, E.; Vargas, C.; Schmitz, J. E.; Zhu, Y.; Scott, T. A.; House, S.; Talbot, H. K.; Stockwell, M. S.; Mellis, A. M.
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Background: Oseltamivir is an antiviral medication for influenza that can reduce the duration of symptoms and may lower the risk of some complications. Recommendations for use of oseltamivir include in the outpatient setting for individuals at higher risk of developing influenza complications. Objectives: To describe oseltamivir initiation and treatment completion among influenza-positive outpatients and identify factors associated with each. Methods: In a U.S. outpatient household transmission study, index participants with laboratory-confirmed influenza provided up to 12 days of detailed information on medication use. We described oseltamivir initiation among index cases and treatment course completion of [≥] 10 doses among cases who initiated oseltamivir. We used unadjusted and adjusted logistic regression to identify factors associated with initiation and course completion. Results: Among 823 enrolled index cases, 324 (39%) initiated oseltamivir treatment. Of 406 persons at higher risk for influenza complications, 172 (42%) initiated treatment. Oseltamivir initiation was lowest among children aged 2 to < 5 years (19%) compared to all other age groups. Among 313 cases who initiated oseltamivir, 42% completed the recommended treatment course of [≥] 10 doses. Among 163 individuals at higher risk of influenza complications, 69 (42%) completed the recommended treatment course of [≥] 10 doses. Children < 2 years were significantly less likely to complete treatment compared to adults aged 18-50 years (aOR: 0.21, 95% CI: 0.04, 0.78, p= 0.030); reasons for discontinuation could not be determined. Conclusions: These findings reveal differences in oseltamivir treatment in an outpatient setting among groups at higher risk for influenza complications.
Dani, H. A.; Njau, P.; Sangeda, R. Z.
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BackgroundDolutegravir (DTG)-based regimens are currently the preferred first-line therapy in many HIV programs; however, the influence of baseline advanced HIV disease (AHD) on virologic outcomes in routine national data in the DTG era remains unclear. MethodsWe conducted a retrospective cohort analysis using routinely collected data from Tanzanias National AIDS, STIs, and Hepatitis Control Programme (NASHCoP) database (2017-2021). A simple random sample of 50,000 patients was drawn from the de-duplicated national dataset, yielding 49,863 patients after data processing. The analytic cohort included 4,044 patients with baseline CD4 and endpoint viral load measurements. Viral load suppression was defined as <1000 copies/mL. Associations between baseline AHD, regimen status, and suppression were assessed using risk ratios and multivariable Poisson regression models, including an interaction term between AHD and DTG. ResultsOverall viral load suppression was 89.2% (3,607/4,044). Patients with baseline AHD had lower suppression than those without AHD (81.3% vs. 91.1%; RR 0.48, 95% CI 0.40-0.57). Suppression was higher among patients receiving DTG-based regimens than among those receiving non-DTG regimens (91.5% vs. 77.2%; RR 2.67, 95% CI 2.23-3.20). In the adjusted analysis, baseline AHD remained associated with reduced suppression (aRR 0.89, 95% CI 0.86-0.92), whereas DTG use was associated with improved suppression (aRR 1.15, 95% CI 1.10-1.20). A significant interaction between AHD and DTG was observed (aRR 1.40, 95% CI 1.20-1.63), indicating that the relative benefit of DTG was greater among patients with baseline AHD. ConclusionsAlthough viral load suppression was high in this Tanzanian routine-care cohort, patients with baseline AHD had poorer outcomes. DTG-based regimens were associated with improved overall suppression, with a greater relative benefit among patients with advanced disease. These findings support the continued prioritization of DTG-based therapy and reinforce the importance of early diagnosis and targeted management of patients with AHD.
Mullen, B.; Githua, J.; Escudero, J. N.; Mecha, J.; Kijaro, L.; Ndunge, M.; Muriithi, M.; Kibet, I.; John-Stewart, G.; Maleche-Obimbo, E.; Nduba, V.; LaCourse, S. M.
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Tuberculosis (TB) is a significant cause of morbidity and mortality in children and adolescents, causing 172,000 deaths in 2024 in children and adolescents worldwide. Diagnostic challenges are pronounced in pediatrics, in which collecting respiratory specimens is challenging and TB is often paucibacillary, leading to delayed diagnosis and increased mortality. We describe the protocol and methodology of the Pediatric TB Diagnostic (PDTBDx) cohort, a study with the primary aim of evaluating non-sputum-based TB diagnostics for diagnosis and treatment response in children. This is a prospective observational cohort study of >400 children recruited from inpatient and outpatient clinical sites in Nairobi, Kenya. Children <15 years presenting to study clinical sites with TB symptoms will be considered for enrollment as symptomatic participants. Enrolled participants will undergo rigorous clinical assessment and longitudinal follow-up to ensure appropriate diagnostic classification by NIH consensus statement guidelines for pediatric TB. Baseline evaluation includes symptom assessment, chest x-ray, HIV testing, respiratory TB culture and GeneXpert Ultra, and urine LAM. Subsequent visits occur at week 2, months 1, 2, 4, 6,12 and 24. Blood and urine specimens will be collected at baseline and at follow-up visits for storage for evaluation of novel diagnostic assays, including exosome-based and CRISPR-based TB biomarkers. This large, prospective cohort of pediatric participants with and without TB follows a consistent and rigorous protocol for diagnosing childhood TB, in concordance with internationally recognized guidelines. Assays evaluated in PDTBDx will guide improved diagnostic strategies for pediatric TB.
Ho, M. Q.; Duong, T. B.; Nguyen, T. L. N.; Tri, N. S.; Bui, T.; Thai, T. T.; Muscatello, D. J.; Sunjaya, A. J.; Chen, S.; Nguyen, N. T.; Nguyen, T. M.; Nguyen, A. T. K.; Duong, C. M.
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The A(H1N1)pdm09 virus remains a major global health threat. This study examined the burden of ICU admission, mortality, and associated predictors among patients with A(H1N1)pdm09 pneumonia in a leading center for infectious diseases in Vietnam. Information on demographic, clinical, and laboratory characteristics, and outcomes was retrieved from medical records of adults admitted with influenza A(H1N1)pdm09 during 2009-2019. Among 729 cases, 21.7% (158/729) developed pneumonia. Among 158 pneumonia cases, 36.7% (58/158) developed moderate-to-severe acute respiratory distress syndrome (ARDS), and 15.2% (24/158) received invasive ventilation. ICU admission and mortality rates were 48.7% (77/158, 95%CI 41.1-56.5%) and 8.2% (13/158, 95%CI 4.9-13.6%), respectively. Predictors of ICU admission included being >60 years old (adjusted OR [AOR] 13.864, 95%CI 2.185-87.956, P=0.005), comorbidities (AOR 6.527, 95%CI 1.710-24.915, P=0.006), AST (AOR 1.013, 95%CI 1.001-1.025, P=0.029), and moderate-to-severe ARDS (AOR 14.027, 95%CI 4.220-46.627, P<0.001). Predictors of mortality were invasive ventilation (AOR 55.355, 95%CI 1.486-2062.375, P=0.030) and double-dose oseltamivir or combination therapy (AOR 32.625, 95%CI 1.594-667.661, P=0.024). In conclusion, mortality is not rare in A(H1N1)pdm09 infection. Monitoring of older patients and those with comorbidities, liver enzyme elevation, or moderate-to-severe ARDS is essential for the timely detection of complications requiring intensive care.
Ponce, L. J.; Xu, B.; Choo, E. L. W.; Chow, J. Y.; Rayapati, R.; Ling, B. Z. M.; Wee, L. E.; Li, R.; Lye, D. C. B.; Ooi, E. E.; Tan, K. B.; Lim, J. T.
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Background Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes-borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions. Methods We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when comparable effect estimates were available (PROSPERO #CRD420251124994). Findings 51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12-4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76-0.89]) and composite outcomes (RR:0.88 [0.82-0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01-1.78]), dementia (HR:1.61 [1.10-2.35]), autoimmune (RR:1.39 [1.17-1.67]), cardiovascular (HR:1.51 [1.27-1.80]), psychiatric (HR:1.17 [1.07-1.28]), and any sequelae (HR:1.19 [1.13-1.25]) versus those without prior infection. Interpretations Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.
Walsh, S.; Hahn, W. O.; Williams, W. B.; Hyrien, O.; Yu, P.-C.; Parks, K. R.; Edwards, R. J.; Parks, R.; Barr, M.; Polakowski, L. L.; Tindale, I.; Jones, M.; Yurdadon, C.; Burnham, R.; Yeh, C.-H.; Heptinstall, J.; Seaton, K.; Andriesen, J.; Sagawa, Z.; Miner, M. D.; De Rosa, S.; McElrath, M. J.; Corey, L.; Tomaras, G. D.; Montefiori, D. C.; Haynes, B. F.; Mayer, K. H.; Baden, L. R.
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Background: Induction of HIV envelope (Env)-specific broadly neutralizing antibodies (bnAbs) is considered a key objective for HIV-1 vaccine development. One approach is to vaccinate with HIV Env immunogens that initially target the naive B cell receptors of a bnAb type and boost with a series of HIV Env variants. We chose a priming immunogen, the CH505 transmitted/founder Env with high affinity for the naive B cell receptor of the prototype CD4 binding site (bs) bnAb lineage, CH103, as a candidate priming immunogen to induce the initial critical step in CD4bs bnAb development. Methods: HVTN 300 is a first-in-human, open-label Phase 1 study evaluating the safety and immunogenicity of a CH505 TF chimeric (ch) Trimer adjuvanted with 3M-052-AF (a TLR7/8 agonist) + Alum. The immunogen is a recombinant, stabilized chimeric Env trimer protein with the N-terminal sequence of CH505 TF gp120 Env transplanted into the BG505 SOSIP sequence. Participants received the adjuvanted protein administered in both deltoid muscles at months 0, 2, 4, 8, and 12. Results: Adults (n=18) aged 18 to 55 were screened at a single site in Boston, USA, and 13 were enrolled. Local and systemic reactogenicity was typically mild to moderate. One participant had severe pain/tenderness, and five participants reported transient severe systemic symptoms at least once. Five participants chose to stop further vaccination due to reactogenicity. No vaccine-related SAEs occurred. Vaccine-specific B-cell response rates reached 100% two weeks post third and fifth vaccinations. Antibody blocking experiments with monoclonal antibodies demonstrated that most participants had antibodies directed to the CD4bs. Four out of 11 participants had serum neutralization signatures for CD4bs bnAb precursors. Conclusions: No safety concerns were identified. The adjuvanted CH505 TF chTrimer elicited serum antibodies capable of CD4bs-mediated neutralization against strains designed to detect early precursors of the CD4bs B-cell lineages. Trial Registration: NCT04915768 Disclosure: Presented in part at HIVR4P 2024, Lima, Peru, October 6-10, 2024
Alekhina, N.; Fonseca-Romero, P.; Gesteland, P. H.; Brintz, B. J.; Leber, A. L.; Jackson, J. T.; Dien Bard, J.; Kanwar, N.; Festekjian, A.; Larsen, C.; Chapin, K. C.; Selvarangan, R.; Soisson, S.; Pavia, A. T.; Leung, D. T.
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Infectious gastroenteritis (IGE) is a major cause of pediatric morbidity globally, with viral pathogens accounting for a substantial proportion of cases. While seasonal patterns of viral IGE are well recognized, the association between specific environmental exposures, such as ambient temperature, and viral IGE has not been fully quantified. First, we performed a secondary analysis of data from a prospective, multisite study of children presenting to emergency departments at five medical centers across the continental United States, linking individual level laboratory data to environmental exposures, including temperature, humidity, and air pollutants, measured during the 14 days preceding symptom onset. Mixed-effects logistic regression was applied to evaluate the association between viral IGE and environmental exposures, adjusting for site-level clustering and patient age. Among 868 children with IGE, higher ambient temperature was inversely associated with viral etiology (OR 0.50, 95% CI 0.36-0.68, p < 0.001). We did not find statistically significant associations between other environmental variables and viral IGE. Then, to contextualize these individual-level findings in children, we examined all-ages population-level surveillance data from GermWatch, a regional laboratory testing-based infectious disease surveillance system, which demonstrated concordant declines in viral pathogen detection with increasing temperature. These findings support the association of weather with viral transmission patterns. Incorporating environmental context into clinical decision-making may improve diagnostic stewardship and support more effective resource allocation during periods of increased viral IGE prevalence.
Bott, H.; Pei, R.; Murphy, M. E.; Shi, T.; Ho, A.
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BackgroundBacterial co-infection contributes substantially to influenza-associated morbidity and mortality. Patterns of viral circulation, diagnostic testing and antimicrobial use changed markedly during the COVID-19 pandemic, yet contemporary estimates of bacterial co-infection and antimicrobial use in influenza have not been synthesised. ObjectivesTo estimate the pooled prevalence of microbiologically confirmed bacterial co-infection among hospital-attended patients with laboratory-confirmed influenza. Secondary objectives were to characterise co-infecting bacterial pathogens, quantify antimicrobial prescribing overall and across key subgroups. This study was registered with PROSPERO (CRD420251072782). Data sources and eligibilityWe searched Embase (Ovid), MEDLINE, PubMed, Scopus, and Web of Science to 15th June 2025 for English-language studies including [≥]50 hospital-attended patients with laboratory-confirmed influenza and reporting bacterial co-infection. MethodsPooled prevalence estimates and antimicrobial prescription proportions were calculated using a generalised linear mixed model with logit link. Subgroup analyses included age group, clinical setting, and seasonal vs. pandemic influenza. Risk of bias was assessed using ROBINS-E and certainty of evidence using GRADE. ResultsNinety-three studies from 30 countries, comprising 111,889 patients with influenza, met inclusion criteria; 9,899 had confirmed bacterial co-infection. The pooled prevalence was 17.3% (95%CI 13.6-21.7%; I2=99.2%). Prevalence was higher in ICU compared to non-ICU settings (28.3% vs. 13.6%). The most frequently identified bacterial pathogens were Streptococcus pneumoniae (35.7%) and Staphylococcus aureus (30.3%). Antimicrobial use, reported in 38 studies, was high (pooled prevalence 88.1%, 95%CI 76.0-94.5%; I2=99.9%), and was more common in adults than children (97.8% vs 65.0%), and in ICU compared with non-ICU settings (96% vs 81%). ConclusionsBacterial co-infection was identified in approximately one in six hospital-attended influenza cases, yet antimicrobial prescribing is near-universal. Substantial heterogeneity and diagnostic variability constraint interpretation but underscore persistent challenges in clinical decision-making. These findings support strengthened diagnostic capacity and antimicrobial stewardship to optimise management of suspected influenza-associated bacterial co-infection.
Neveux, M. R.; Hylin, R.; Ruiz Gonzalez, V.; Lopez Parra, A. P.; Onoja, A.; Sirivichayakul, S.; Sulaimon, A. A.; Rwibasira, G.; Ochwoto, M.
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IntroductionDiagnostics have become the fundamental backbone of HIV prevention, treatment and long-term retention in care, and are critical to achieving the 95-95-95 UNAIDS targets. To effectively reach underserved and remote populations, diagnostic technologies must be cost-effective, robust, user-friendly and suitable for settings with limited infrastructure. Among available testing modalities, rapid diagnostic tests (RDTs) play a central role in expanding HIV testing coverage. Earlier generations of RDTs were limited by their inability to detect acute HIV, with limited ability to detect p24 antigen (Ag), an early marker of HIV infection, which is expected to shorten the diagnostic window to two-to-three weeks. The introduction of fourth-generation RDTs, which detects both chronic and acute HIV infection through p24 Ag detection, was designed to ensure that the traditional diagnostic window of two-to-three months is shortened to approximately two-to-three weeks. However, integrating these assays into existing testing algorithms requires clear evidence that they meet high standards of quality and performance. This systematic review aims to assess the performance of WHO-prequalified fourth-generation Ag/Ab RDTs. MethodsWe performed a systematic search across six databases to identify studies evaluating Ag/Ab RDTs against laboratory reference standards in individuals aged 12 years and older, spanning 1 January 2010 to 31 December 2025. Outcomes were limited to measures of diagnostic accuracy. A meta-analysis focusing exclusively on WHO-prequalified fourth-generation RDTs was performed using a bivariate random-effect model. Results1,932 records were screened, of which 31 diagnostic accuracy studies from 19 countries were included. 15 studies used US-only approved products, 12 used WHO-prequalified products and four used commercially discontinued products. The pooled sensitivity of WHO-prequalified Ag/Ab RDTs for acute HIV infection (AHI) was 94% (95% CI: 86%-99%). An RNA threshold of [≥] 1,000,000 copies/mL was used as a proxy for high viraemia and used as a cut-off for the following analyses. The cut-off based analysis is considered more suited to decision-making, as it focuses on cases most likely to be associated with higher viraemia and greater potential for detection during the p24 Ag window. When using enzyme immunoassay (EIA) as the reference standard, the pooled p24 Ag sensitivity was 76% (95% CI: 62%-88%), and the pooled p24 Ag sensitivity when using nucleic acid amplification test (NAAT) as the reference standard was 75% (95% CI: 41%-97%). In the general population, the pooled sensitivity for p24 antigen detection was 77% (95% CI: 60%-92%). Amongst risk populations, only three studies had available raw data, and the pooled sensitivity was 62% (95% CI: 10%-97%). In plasma and serum specimens, pooled p24 Ag sensitivity was 74% (95% CI: 57%-88). DiscussionCollectively, these findings indicate that WHO-prequalified fourth-generation Ag/Ab RDTs can function as a scalable frontline screening tool, particularly in low- and middle-income countries, while offering incremental holistic detection through p24 Ag. Their effective deployment, however, depends on maintaining standard algorithm safeguards, including repeat testing and targeted laboratory referral when acute infection is suspected. ConclusionsResults from this meta-analysis support the use of WHO-prequalified fourth-generation Ag/Ab RDTs for general population screening. From a programmatic perspective, the added value of WHO-prequalified fourth-generation RDTs lies in their ability to combine rapid, decentralized access to testing, with incremental yet impactful improvements in holistic detection.
Karichu, J. K.; Pennington, M.; Lander, K.; Smith, T. T.; Thornberg, A.
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Introduction Data on bloodstream infections (BSI) indicate a growth in incidence over time. This analysis utilised national data from England and the best available United States (US) evidence to predict BSI incidence over the years 2025 to 2029. The analysis utilised evidence on the cost-effectiveness of molecular rapid diagnostic tests (mRDT) to estimate the cost and mortality associated with BSI, and the potential for increased use of mRDT to save lives. Methods Data on BSI incidence by age group and sex for England in 2017 and the US (Minnesota) for 2003 to 2005 were combined with demographic projections over the years 2025 to 2029 to estimate the number of BSIs. Published costs and mortality associated with BSI, according to the method of identification of the pathogen, were used to estimate the lives saved and the cost impact of widespread use of mRDT in England and the US. Results BSI cases in England and the US are predicted to total 1.02 million and 6.24 million over the years 2025 to 2029, associated costs are GBP14.6 million and $221 million, respectively. Expanding the use of mRDT would save 2,219 and 7,554 lives in England and the US, respectively, over a 5-year period and would reduce healthcare expenditure in both countries. Conclusion There is a compelling argument to increase the uptake of mRDT to improve patient outcomes. This analysis demonstrates that expanded mRDT adoption can significantly reduce BSI burden, saving over 9,700 lives and decreasing healthcare expenditure in both countries.
Lewis, N. M.; Cleary, S.; Harker, E. J.; Safdar, B.; Ginde, A. A.; Peltan, I. D.; Gaglani, M.; Columbus, C.; Martin, E. T.; Lauring, A. S.; Steingrub, J. S.; Hager, D. N.; Mohamed, A.; Johnson, N. J.; Khan, A.; Duggal, A.; Wilson, J. G.; Qadir, N.; Busse, L. W.; Kwon, J. H.; Exline, M. C.; Vaughn, I. A.; Mosier, J. M.; Harris, E. S.; Zhu, Y.; Grijalva, C. G.; Halasa, N. B.; Chappell, J.; Surie, D.; Dawood, F. S.; Ellington, S. R.; Self, W. H.
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Background: The U.S. 2024-2025 influenza season was characterized by sustained elevated activity from November 2024 to April 2025, with circulation of both influenza A(H1N1)pdm09 and A(H3N2), the latter of which included some antigenically drifted viruses. Methods: From October 1, 2024, to April 30, 2025, a multistate respiratory virus surveillance network enrolled adults hospitalized with acute respiratory illness in 26 U.S. medical centers. Influenza vaccine effectiveness (VE) against influenza-associated hospitalization and severe in-hospital outcomes was estimated using a test-negative study. The odds of influenza vaccination among influenza-positive case patients and influenza-negative control patients were compared using multivariable logistic regression; VE was calculated as (1-adjusted odds ratio for vaccination) x 100, expressed as a percent. Results: The 2024-2025 seasonal influenza vaccine was effective against influenza-associated hospitalization (VE: 40% [95% confidence interval (CI): 32%-47%]), consistent across age group and influenza A subtypes. Influenza vaccination also reduced the overall risk of all severe in-hospital outcomes evaluated, including standard oxygen therapy (VE: 41% [95% CI: 31%-50%]), non-invasive advanced respiratory support (VE: 38% [95% CI: 19%-52%]), invasive organ support (VE: 58% [95% CI: 44%-69%]), ICU admission (VE: 58% [95% CI: 47%-67%]), and death (VE: 52% [95% CI: 18%-71%]) with effectiveness varying by influenza A subtype and age. Conclusions: Influenza vaccination reduced the risk of influenza-related hospitalization and severe in-hospital outcomes in adults during the severe 2024-2025 influenza season compared to those not vaccinated.
Shireman, J.; Mukherjee, N.; Brackman, K.; Kurtz, N.; Patniak, A.; McCarthy, L.; Gonugunta, N.; Ammanuel, S.; Dey, M.
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ObjectivesAcademic medical institutions are the gatekeepers of the physician workforce and shape the future of medicine by regulating medical school admissions as well as residency training. Although broadly the field of medicine is seeing more representation from traditionally underrepresented groups, the critical decision-making platform of academic medicine continues to be uncharacteristically homogeneous, represented mainly by white males. This is even more pronounced in surgical subspecialties, such as academic neurosurgery. This study aims to quantify this phenomenon, uncover its driving factors, and define opportunities for improvement. MethodsUsing a mixed research methodology, academic neurosurgical faculty in the U.S were identified, and their demographic data was collected. An internet search using Google Scholar and Scopus was conducted to determine scholarly activity using number of publications and h-index. ResultsWe found a significant increase in female faculty in academic neurosurgery within the last decade. Comparing the faculty rank amongst male and female faculty, we found that the majority of female faculty are at the assistant professor level (n=36/79; 45.6%) while male faculty are more at the full professor rank (n=265/582; 45.5%). A similar trend was seen for under-represented minority neurosurgery faculty. Strong scholarly activity corelated with a departmental chair position for male faculty, however, this trend was not true for female faculty. There was a significant difference in the number of publications and h-index in female vs male faculty, but only when including male faculty outliers at the full professor level. ConclusionSlowly but steadily, academic neurosurgery is making progress towards a more diverse and representative workforce in the U.S that better reflects the patient population. Facilitating timely progression of females and URM neurosurgeons into senior professorship and academic leadership roles will further advance this essential progress.
Jefferies, T. J.; LaVigne, M. K.
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Introduction: Early exposure to otolaryngology (ENT) procedural skills in undergraduate medical education is limited by patient safety concerns, restricted clinical opportunities, and the cost of commercial simulators. As a result, essential ENT skills are often underrepresented in structured, hands-on curricula for medical students. Methods: We developed a low-cost, multistation ENT simulation curriculum consisting of five reproducible task trainers: ear examination and otologic procedures, mirror laryngoscopy, rigid and flexible endoscopic navigation, introductory mastoid drilling, and emergency cricothyrotomy. The curriculum was delivered as a 2-hour, faculty-led workshop during a third-year medical student otolaryngology rotation. Learners rotated through stations in small groups. Pre- and post-workshop surveys assessed self-reported anatomical familiarity, procedural confidence, and educational value using a 5-point Likert scale, with additional qualitative feedback collected. Results: All participants completed pre- and post-workshop evaluations. Learners demonstrated increased confidence across all assessed anatomical and procedural domains, including otoscopy, endoscopy, mirror laryngoscopy, mastoid drilling orientation, and cricothyroid membrane identification. Educational value ratings were high across all stations, with mean scores ranging from 4.33 to 5.00. Qualitative feedback emphasized the realism, accessibility, and benefit of hands-on practice in a low-stakes learning environment. Conclusion: This low-cost, multistation ENT simulation curriculum provides a feasible and reproducible approach for introducing foundational otolaryngology skills to medical students. The structured format and affordable models support early procedural exposure and may enhance learner preparedness prior to supervised clinical encounters, particularly in settings with limited simulation resources.
Dolin, P.; Keogh, K. A.; Rowell, J.; Edmonds, C.; Kielar, D.; Meyers, J.; Esterberg, E.; Nham, T.; Chen, S. Y.
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PurposeWe evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). MethodsPatients with newly diagnosed EGPA (2017-2021), [≥]12 months pre-diagnosis health plan enrollment, and [≥]1 inpatient or [≥]2 outpatient claims with an EGPA diagnosis were included. Follow-up was from EGPA diagnosis until disenrollment or database end. HCRU and health insurer payment costs during follow-up were compared with those for matched cohorts of general insured patients without EGPA (comparison A) and without EGPA but with severe uncontrolled asthma (SUA; comparison B). ResultsIn comparison A, all-cause HCRU was higher in the EGPA cohort (n = 213) versus matched patients (n = 779) for all clinical encounters/pharmacy claim types; annualized, mean total all-cause costs were 16-fold higher ($117,563/patient) versus matched patients ($7,520/patient). In comparison B, all-cause HCRU was higher for the EGPA cohort (n = 182) versus the matched SUA cohort (n = 640) for all clinical encounters/pharmacy claim types, with 5-fold higher mean total all-cause costs ($118,127/patient vs $22,286/patient). In both EGPA cohorts, HCRU and associated costs increased between the baseline and follow-up periods. ConclusionsThese findings highlight the need for more effective treatments to reduce the clinical and economic burden of EGPA.
Kulkarni, D.; Osei-Yeboah, R.; Templeton, K.; Nair, H.
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Background: Human metapneumovirus (hMPV) is commonly associated with respiratory tract infections (RTIs) in young children. Methods: We estimated the annual hospital incidence of hMPV RTIs in children under 5 years in Scotland from 2017 to 2023 using national hospital and laboratory data. Incidence outside Lothian, where testing practices were uncertain, was extrapolated from Lothian laboratory data, where hMPV testing was advised for all RTI admissions. We also examined the severity and mortality of laboratory-confirmed hMPV cases. We developed similar estimates for RSV and Influenza A for comparison. Results: This analysis included 1,462 laboratory-confirmed hMPV hospitalisations in children aged under 5 years. The extrapolated hMPV hospital incidence ranged from 19 per 100,000 to 537 per 100,000 in children aged under 5 years. The extrapolated incidence was two to three times higher than that based on laboratory-confirmed data. Hospital incidence was higher in infants than in toddlers. hMPV incidence dropped substantially during the 2020/21 season, followed by a rebound during the 2021/22 season. About 10% of hMPV RTI hospital admissions required hospital stay [≥]5 days, but <1% required intensive care unit admissions or resulted in in-hospital death. RSV hospital incidence appeared substantially higher than the hMPV hospital incidence in this population. Conclusions: hMPV RTIs contribute to a substantial hospital burden in young children in Scotland. However, the RSV RTI burden is likely to be higher in the population unvaccinated against both viruses. Improved surveillance and diagnosis strategies are required to develop robust hospital burden estimates.
Lessler, J.; Smith, C. P.; Das, P.; Sykes, A. L.; Urbinati, A.; Geith, K.; Powers, K. A.; Davis, J. T.; Kern-Allely, S. C.; Vega Yon, G. G.; Lofgren, E. T.; Pearson, C. A. B.; Vespignani, A.
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Background: The 2026 FIFA World Cup may bring over one million visitors to North America from around the globe to participate in mass gathering events. The nature of the event and recent news have raised concerns for some that the tournament could lead to infectious disease outbreaks or fuel existing epidemics. Objective: To systematically assess the infectious disease threat posed to the United States by the tournament. Design: A multi-institutional team evaluated pathogen-specific risk across three dimensions: importation, outbreak potential, and impact to identify a priority pathogen list. A systematic screening protocol ensured common criteria and that pathogen information was collected when necessary to inform inclusion. Results: Increased risk from the World Cup is near zero for 63 of 77 evaluated pathogens. Pathogens were predominantly excluded as threats due to low excess importation risk and low outbreak potential if introduced. The remaining priority pathogens fall into five categories: (a) mosquito borne pathogens with the potential for sustained transmission in some host cities, (b) seasonal respiratory viruses, (c) chronic infections with high prevalence outside the United States, (d) pathogens present in the United States with likely increased transmission at World Cup activities, and (e) high-consequence infectious threats. Limitations: Data availability is variable across diseases. Impact calculations may not reflect actual costs to host cities. Disease incidence in World Cup travelers may differ from national incidence rates. Conclusion: While infectious disease outbreaks at the 2026 FIFA World Cup are possible, in an already highly connected world where large gatherings are frequent, the elevated risk from the tournament is not as extreme as it first may seem.
Saura-Lazaro, A.; Adolfo Bila, D.; Van den Bogaart, E.; Myburgh, H.; Fisher-Cunhete, M.; Vaz, P.; Paulussen, R.; Viljoen, L.; Rinke de Wit, T. F.; Naniche, D.
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Introduction: Viral load (VL) monitoring is the gold standard for antiretroviral therapy (ART) monitoring. Still, due to limited funds and infrastructure, many people living with HIV (PLHIV) in low- and middle-income countries do not receive timely VL testing. We evaluated the clinical performance and end-user acceptability of a prototype interferon gamma-induced protein 10 (IP-10) point-of-care (POC) test as a rule-out triage tool to identify individuals unlikely to have unsuppressed VL in PLHIV in Mozambique. Methods: A mixed-methods study was conducted between November 2023 and November 2024 at two primary healthcare facilities in Maputo Province. We enrolled 1,057 PLHIV on ART from stable and specialized risk clinics. Clinical performance of the IP-10 POC test (index test) was compared against plasma HIV VL (reference test; unsuppressed defined as >1000 copies/mL). Socio-demographic and clinical predictors of false-positive results were identified using multivariable logistic regression. Immediate acceptability was assessed through exit interviews on a subset of 43 PLHIV. Results: Among participants (71.7% female; median age 41.4 years), 12.0% had unsuppressed VL. The IP-10 POC test demonstrated high sensitivity (90.6%) and moderate specificity (35.6%). Specificity was higher in clinics treating stable patients (44.5% 95%CI: 39.7-49.3) compared to specialized risk clinics (26.5% 95%CI: 21.1-28.9). The proportion of false-positive results was also higher in patients attending specialized risk clinics. Independent predictors of false positivity included enrolment in a one-stop TB/HIV clinic (aOR=2.99 95%CI: 1.09-8.15), cotrimoxazole use (aOR=2.16, 95% CI: 1.13-4.13), and obesity (aOR=3.47 95%CI: 1.74-6.93). Acceptability was high: 70% of participants appreciated the test simplicity and rapid results, and 95.3% expressed interest in future testing. Most patients preferred finger-prick collection over venous draws. Conclusions: The IP-10 POC test is a highly sensitive triage tool, demonstrating superior performance among stable PLHIV enrolled in differentiated service delivery models like six-month multi-month dispensing. While factors associated with co-infections can reduce specificity, the test's high acceptability and potential to reduce confirmatory VL test demand suggests it could serve as a viable triage strategy for optimizing resources particularly in stable care pathways with a lower prevalence of inflammatory comorbidities. This could enable health systems to reallocate intensive monitoring toward higher-risk populations.