Enhancing trauma care in Ukraine amid conflict: A successful implementation of the modified advanced trauma life support course in an active war zone.

BACKGROUND: Following the 2022 Russian invasion, Ukraine's healthcare system suffered extensive damage, with over 1000 medical facilities destroyed, exacerbating the trauma care crisis. The absence of standardized trauma training left Ukrainian healthcare providers ill-equipped to manage the surge in trauma cases amid conflict. To bridge this gap, we implemented advanced trauma life support (ATLS) courses in Ukraine amid active warfare, aiming to enhance trauma care expertise among healthcare professionals. METHODS: A consortium, including the International Medical Corps, Harvard Humanitarian Initiative, and others, responded to a request from the Ukrainian Ministry of Health. The ATLS curriculum, translated into Ukrainian, guided the training, with US-based instructors sent to Ukraine for teaching. Despite logistical challenges, such as missile attacks and curfews, the courses ran in multiple Ukrainian cities over 3 months. Course effectiveness was evaluated through pre- and post-course knowledge tests, self-efficacy surveys, and satisfaction assessments. RESULTS: Ten ATLS courses trained 213 Ukrainian healthcare providers across five deployments. Significant improvements in knowledge scores (p < 0.05) and enhanced self-reported confidence in trauma management were observed. Notably, no casualties were reported among instructors or students, highlighting program safety despite security challenges. CONCLUSIONS: Our study demonstrates successful ATLS course implementation in an active war zone, filling a critical gap in trauma education in Ukraine. Despite challenges, the program significantly enhanced participants' trauma care knowledge and confidence. Collaboration between international and local partners was pivotal. This model can serve as a valuable framework for trauma education globally, improving outcomes in conflict zones and resource-limited settings.

Evaluation of Chemical, Biological, Radiological, Nuclear, Explosives (CBRNE) Knowledge Change and Skills Confidence Among Frontline-Line Providers During the Russia-Ukraine War.

OBJECTIVE: The aim of this study was to evaluate the change in knowledge and skill confidence after implementation of a chemical, biological, radiological, nuclear, and explosive (CBRNE) training course during the Russia-Ukraine War. METHODS: Pre/post-test study in the Ukrainian cities of Kyiv, Dnipro, Zaporizhzhia, and Odesa. Fifteen CBRNE courses were conducted over a 3-mo period, August to October 2022. Change in knowledge and skills confidence were evaluated with pre/post-course written exams and practical skill assessments that were observed during the training exercises. Changes were analyzed based on nonparametric Wilcoxon matched-pairs signed-rank testing. Pre/post self-efficacy surveys were analyzed with McNemar's test for paired data. Course evaluations were conducted with standardized questions which assessed instruction quality, teaching relevance, knowledge gained, and post-course skills confidence. RESULTS: A total of 523 participants registered and completed 1 of the 15 courses. Overall mean pre-course test score: 57.8% (SD 20.7%); mean post-course test score: 81.4% (SD 11.3%); participants with increasing test scores: 90.7%; mean difference in score (95% confidence interval) 23.6% (21.2%-25.9%), P < 0.0001. Pre/post self-efficacy surveys (4-point Likert scale) noted participants recognized signs and symptoms of a CBRNE incident, and necessary skills to manage CBRNE exposures, P < 0.0001. CONCLUSIONS: The implementation of this CBRNE course for front-line providers in Ukraine was successful. To our knowledge, it was the first implementation of a field course during the current Russian-Ukraine war. Future research should evaluate knowledge retention and impact of our innovative Train-the-Trainer model. Further iterations should emphasize expanding the quantity of training equipment and practical skill sessions.

Longitudinal SARS-CoV-2 Nucleocapsid Antibody Kinetics, Seroreversion, and Implications for Seroepidemiologic Studies.

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

Respiratory viruses in rural Zambia before and during the COVID-19 pandemic.

OBJECTIVES: With the emergence of the COVID-19 pandemic, restrictions were implemented globally to control the virus. Data on respiratory pathogens in sub-Saharan Africa during the COVID-19 pandemic are scarce. This analysis was conducted to evaluate patterns of respiratory pathogens in rural Zambia before and during the first year of the pandemic. METHODS: Surveillance was established in December 2018 at Macha Hospital in southern Zambia. Patients with respiratory symptoms in the outpatient and inpatient clinics were recruited. Nasopharyngeal samples were collected and tested for respiratory pathogens. The prevalence of respiratory symptoms and pathogens was evaluated and compared in the first (December 10, 2018-December 9, 2019) and second (December 10, 2019-November 30, 2020) years of surveillance. RESULTS: Outpatient visits and admissions for respiratory illness significantly decreased from the first to second year, especially among children. SARS-CoV-2 was not detected from any participants in Year 2. Among outpatients and inpatients with respiratory symptoms, the prevalence of respiratory syncytial virus and influenza viruses decreased from the first to second year. In contrast, the prevalence of rhinovirus/enterovirus, metapneumovirus and parainfluenza virus increased. CONCLUSIONS: The epidemiology of respiratory viruses in rural Zambia changed during the first year of the COVID-19 pandemic, suggesting that public health interventions may have had an impact on the introduction and circulation of respiratory pathogens in this area.

Declining HIV incidence in sub-Saharan Africa: a systematic review and meta-analysis of empiric data.

INTRODUCTION: UNAIDS models suggest HIV incidence is declining in sub-Saharan Africa. The objective of this study was to assess whether modelled trends are supported by empirical evidence. METHODS: We conducted a systematic review and meta-analysis of adult HIV incidence data from sub-Saharan Africa by searching Embase, Scopus, PubMed and OVID databases and technical reports published between 1 January 2010 and 23 July 2019. We included prospective and cross-sectional studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting greater than or equal to three incidence measurements since 2010 and assessed trends within them. RESULTS: Total 291 studies, including 22 sub-Saharan African countries, met inclusion criteria. Most studies were conducted in South Africa (n = 102), Uganda (n = 46) and Kenya (n = 41); there were 26 countries with no published incidence data, most in western and central Africa. Data were most commonly derived from prospective observational studies (n = 163; 56%) and from geographically defined populations with limited demographic or risk-based enrolment criteria other than age (i.e., general population studies; n = 151; 52%). Across general population studies, average annual incidence declines since 2010 were 0.12/100 person-years (95% CI: 0.06-0.18; p = 0.001) among men and 0.10/100 person-years (95% CI: -0.02-0.22; p = 0.093) among women in eastern Africa, and 0.25/100 person-years (95% CI: 0.17-034; p < 0.0001) among men and 0.42/100 person-years (95% CI: 0.23-0.62; p = 0.0002) among women in southern Africa. In nine of 10 studies with multiple measurements, incidence declined over time, including in two studies of key populations. Across all population risk groups, the highest HIV incidence estimates were observed among men who have sex with men, with rates ranging from 1.0 to 15.4/100 person-years. Within general population studies, incidence was typically higher in women than men with a median female-to-male incidence rate ratio of 1.47 (IQR: 1.11 to 1.83) with evidence of a growing sex disparity over time. CONCLUSIONS: Empirical incidence data show the rate of new HIV infections is declining in eastern and southern Africa. However, recent incidence data are non-existent or very limited for many countries and key populations.

Facility-based surveillance for influenza and respiratory syncytial virus in rural Zambia.

BACKGROUND: While southern Africa experiences among the highest mortality rates from respiratory infections, the burden of influenza and respiratory syncytial virus (RSV) in rural areas is poorly understood. METHODS: We implemented facility-based surveillance in Macha, Zambia. Outpatients and inpatients presenting with influenza-like illness (ILI) underwent testing for influenza A, influenza B, and RSV and were prospectively followed for 3 to 5 weeks to assess clinical course. Log-binomial models assessed correlates of infection and clinical severity. RESULTS: Between December 2018 and December 2019, 17% of all outpatients presented with ILI and 16% of inpatients were admitted with an acute respiratory complaint. Influenza viruses and RSV were detected in 17% and 11% of outpatient participants with ILI, and 23% and 16% of inpatient participants with ILI, respectively. Influenza (July-September) and RSV (January-April) prevalence peaks were temporally distinct. RSV (relative risk [RR]: 1.78; 95% confidence interval [CI] 1.51-2.11), but not influenza, infection was associated with severe disease among patients with ILI. Underweight patients with ILI were more likely to be infected with influenza A (prevalence ratio [PR]: 1.72; 95% CI 1.04-2.87) and to have severe influenza A infections (RR: 2.49; 95% CI 1.57-3.93). CONCLUSIONS: Populations in rural Zambia bear a sizeable burden of viral respiratory infections and severe disease. The epidemiology of infections in this rural area differs from that reported from urban areas in Zambia.

Nosocomial Respiratory Infections in a Rural Zambian Hospital.

The burden of nosocomial respiratory infections in rural southern Africa is poorly understood. We established a surveillance program at a rural Zambian hospital to detect influenza-like illness (ILI) and respiratory infections among hospitalized patients and a cohort of healthcare workers (HCWs). Nasopharyngeal specimens from symptomatic patients and HCWs underwent broadly multiplexed molecular testing to detect viruses and atypical bacteria. During 1 year of surveillance, 15 patients (1.7% of admissions) developed ILI more than 48 hours after admission. Among 44 HCWs, 19 (43%) experienced at least one ILI episode, with a total of 31 ILI episodes detected. Respiratory viruses were detected in 45% of patient and 55% of HCW specimens. The cumulative incidence of influenza infection among HCWs over 1 year was 9%. Overall, respiratory viruses were commonly found among patients and HCWs in a rural Zambian hospital with limited infection control infrastructure.

Respiratory pathogen diversity and co-infections in rural Zambia.

OBJECTIVES: The role of respiratory co-infections in modulating disease severity remains understudied in southern Africa, particularly in rural areas. This study was performed to characterize the spectrum of respiratory pathogens in rural southern Zambia and the prognostic impact of co-infections. METHODS: Respiratory specimens collected from inpatient and outpatient participants in a viral surveillance program in 2018-2019 were tested for selected viruses and atypical bacteria using the Xpert Xpress Flu/RSV assay and FilmArray Respiratory Panel EZ. Participants were followed for 3-5 weeks to assess their clinical course. Multivariable regression was used to examine the role of co-infections in influencing disease severity. RESULTS: A respiratory pathogen was detected in 63.2% of samples from 671 participants who presented with influenza-like illness. Common pathogens identified included influenza virus (18.2% of samples), respiratory syncytial virus (RSV) (11.8%), rhinovirus (26.4%), and coronavirus (6.0%). Overall, 6.4% of participants were co-infected with multiple respiratory pathogens. Compared to mono-infections, co-infections were found not to be associated with severe clinical illness either overall (relative risk (RR) 0.72, 95% confidence interval (CI) 0.39-1.32) or specifically with influenza virus (RR 0.80, 95% CI 0.14-4.46) or RSV infections (RR 0.44, 95% CI 0.17-1.11). CONCLUSIONS: Respiratory infections in rural southern Zambia were associated with a wide range of viruses. Respiratory co-infections in this population were not associated with clinical severity.

Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Racial and ethnic disparities in hospital observation in Maryland.

OBJECTIVES: Hospital observation is a key disposition option from the emergency department (ED) and encompasses up to one third of patients requiring post-ED care. Observation has been associated with higher incidence of catastrophic financial costs and has downstream effects on post-discharge clinical services. Yet little is known about the non-clinical determinants of observation assignment. We sought to evaluate the impact of patient-level demographic factors on observation designation among Maryland patients. METHODS: We conducted a retrospective analysis of all ED encounters in Maryland between July 2012 and January 2017 for four priority diagnoses (heart failure, chronic obstructive pulmonary disease [COPD], pneumonia, and acute chest pain) using multilevel logistic models allowing for heterogeneity of the effects across hospitals. The primary exposure was self-reported race and ethnicity. The primary outcome was the initial status assignment from the ED: hospital observation versus inpatient admission. RESULTS: Across 46 Maryland hospitals, 259,788 patient encounters resulted in a disposition of inpatient admission (65%) or observation designation (35%). Black (adjusted odds ratio [aOR]: 1.19; 95% confidence interval [CI]: 1.16-1.23) and Hispanic (aOR: 1.11; 95% CI: 1.01-1.21) patients were significantly more likely to be placed in observation than white, non-Hispanic patients. These differences were consistent across the majority of acute-care hospitals in Maryland (27/46). CONCLUSION: Black and Hispanic patients in Maryland are more likely to be treated under the observation designation than white, non-Hispanic patients independent of clinical presentation. Race agnostic, time-based status assignments may be key in eliminating these disparities.

Measles Seroprevalence and Vaccine Responses in Human Immunodeficiency Virus-infected Adolescents and Adults: A Systematic Review.

BACKGROUND: The World Health Organization (WHO) recommends an additional dose of measles-containing vaccine (MCV) for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy following immune reconstitution. We conducted a systematic review to synthesize available evidence regarding measles seroprevalence and measles vaccine immunogenicity, efficacy, and safety in HIV-infected adolescents and adults to provide the evidence base for recommendations on the need for measles vaccination. METHODS: We conducted searches of 8 databases through 26 September 2017. Identified studies were screened independently by 2 reviewers. RESULTS: The search identified 30 studies meeting inclusion criteria. Across studies, measles seroprevalence among HIV-infected adolescents and adults was high (median, 92%; 27 studies), with no significant difference compared to HIV-uninfected participants (10 studies). In 6 studies that evaluated the immunogenicity of MCVs among seronegative HIV-infected adults, measles seropositivity at end of follow-up ranged from 0% to 56% (median, 39%). No severe adverse events were reported following measles vaccination in HIV-infected patients. CONCLUSIONS: Based on similar measles seroprevalence between HIV-infected and HIV-uninfected adolescents and adults, and the low response to vaccination, these studies do not support the need for an additional dose of MCV in HIV-infected adolescents and adults. These findings support WHO guidelines that measles vaccine be administered to potentially susceptible, asymptomatic HIV-infected adults, and may be considered for those with symptomatic HIV infection if not severely immunosuppressed. Measles-susceptible adolescents and adults, regardless of HIV status, may require targeted vaccination efforts to reach critical vaccination thresholds and achieve regional elimination goals.

A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice.

The visual system consists of two major subsystems, image-forming circuits that drive conscious vision and non-image-forming circuits for behaviors such as circadian photoentrainment. While historically considered non-overlapping, recent evidence has uncovered crosstalk between these subsystems. Here, we investigated shared developmental mechanisms. We revealed an unprecedented role for light in the maturation of the circadian clock and discovered that intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for this refinement process. In addition, ipRGCs regulate retinal waves independent of light, and developmental ablation of a subset of ipRGCs disrupts eye-specific segregation of retinogeniculate projections. Specifically, a subset of ipRGCs, comprising ~200 cells and which project intraretinally and to circadian centers in the brain, are sufficient to mediate both of these developmental processes. Thus, this subset of ipRGCs constitute a shared node in the neural networks that mediate light-dependent maturation of the circadian clock and light-independent refinement of retinogeniculate projections.

Hepatitis C virus NS2 protein triggers endoplasmic reticulum stress and suppresses its own viral replication.

BACKGROUND & AIMS: We previously reported that the NS2 protein of hepatitis C virus (HCV) inhibits the expression of reporter genes driven by a variety of cellular and viral promoters. The aim of the study was to determine whether the broad transcriptional repression is caused by endoplasmic reticulum (ER) stress. METHODS: Phosphorylation of the translation initiation factor eIF2α and HCV replication was detected by Western and Northern blot, respectively. De novo protein synthesis was measured by metabolic labeling. Activation of ER stress responsive genes was determined by promoter reporter assay, as well as mRNA and protein measurement by real time PCR and Western blot. RESULTS: Transient or inducible NS2 protein expression increased eIF2α phosphorylation and reduced de novo protein synthesis. It up-regulated promoter activities and transcript levels of ER stress inducible genes including GRP78, ATF6, and GADD153, as well as GRP78 protein level. The same effect was observed when NS2 was synthesized as part of the core-E1-E2-p7-NS2 polypeptide. NS2 protein also inhibited reporter gene expression from the HCV internal ribosome entry site and consequently reduced HCV replication. The full-length HCV replicon activated GRP78, ATF6, and GADD153 promoters more efficiently than the subgenomic replicon lacking the coding sequence for both the structural proteins and NS2. Abrogation of HCV infection/replication, by an inhibitor of the NS3 protease, relieved ER stress. CONCLUSIONS: HCV infection can induce ER stress, with NS2 protein being a major mediator. The stress can be relieved by a feedback mechanism.