Violence against nurses and other healthcare workers is a significant and escalating concern, impeding the provision of safe and effective healthcare services. A majority of nurses experience some kind of violence, including physical and nonphysical assaults during their careers. The consequences of workplace violence extend beyond individual trauma, leading to increased burnout, turnover, and significant financial costs for healthcare systems. Training programs focused on workplace violence prevention (WVP) have become ubiquitous, with elements like situational threat assessment, de-escalation techniques, and physical skills. Studies show that experiential components, such as role play, enhance the effectiveness of these trainings. Virtual Reality (VR) offers a promising solution by providing immersive, interactive training environments that enhance decision-making, physical coordination, and team dynamics. In this article we discuss how VR simulations can replicate real-world settings, allowing healthcare workers to practice and master violence prevention and management skills in a controlled, safe environment. We also describe how VR is scalable and cost-effective, enabling widespread adoption within and across organizations with minimal logistical challenges. Integrating VR into WVP training programs could significantly improve training outcomes, reduce the need for physical and chemical restraints, and ultimately enhance the overall safety and quality of healthcare services.

In both molecular epidemiology and microbial ecology, it is useful to be able to categorize specific strains of microorganisms in either an ingroup or an outgroup in a given population, e.g. to distinguish a pathogenic strain of interest from its non-virulent relatives. An "ingroup" refers to a group of microbes that are the primary focus of study or interest. Conversely, an "outgroup" consists of microbes that are closely-related to, but have evolved separately from, the ingroup. While whole genome sequencing and downstream phylogenetic analyses can be employed to do this, these techniques are often slow and can be resource intensive. Additionally, the laboratory would have to sequence the whole genome to use these tools to determine whether or not a new sample is part of the ingroup or outgroup. Alternatively, polymerase chain reaction (PCR) can be used to amplify regions of genetic material that are specific to the strain(s) of interest. PCR is faster, less expensive, and more accessible than whole genome sequencing, so having a PCR-based approach can accelerate the detection of specific strain(s) of microbes and facilitate diagnoses and/or population studies.

Background: The first licensed malaria vaccine, RTS,S/AS01<inf>E</inf>, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. Method(s): Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01<inf>E</inf> regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. Finding(s): We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01<inf>E</inf> regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01<inf>E</inf> regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1.1-1.6 infections (95% CI union 0.6-2.1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0.0053). Interpretation(s): All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. Funding(s): GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research. Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

BACKGROUND: The first licensed malaria vaccine, RTS,S/AS01(E), confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. METHODS: Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01(E) regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. FINDINGS: We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01(E) regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01(E) regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053). INTERPRETATION: All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. FUNDING: GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.

The use of data analytics has seen widespread application in fields such as medicine and supply chain management, but their application in occupational safety has only recently become more common. The purpose of this scoping review was to summarize studies that employed analytics within establishments to reveal insights about work-related injuries or fatalities. Over 300 articles were reviewed to survey the objectives, scope and methods used in this emerging field. We conclude that the promise of analytics for providing actionable insights to address occupational safety concerns is still in its infancy. Our review shows that most articles were focused on method development and validation, including studies that tested novel methods or compared the utility of multiple methods. Many of the studies cited various challenges in overcoming barriers caused by inadequate or inefficient technical infrastructures and unsupportive data cultures that threaten the accuracy and quality of insights revealed by the analytics.

BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

BACKGROUND: Accreditation Council for Graduate Medical Education (ACGME) work-hour restrictions (WHRs) are intended to improve patient safety by reducing resident fatigue. Compliance with ACGME WHRs is not universal. PURPOSE: The purpose of this study was to identify factors that influence residents' decisions to take a postcall day (PCD) off according to ACGME WHRs. METHODS: Residents (N = 433) at one university were emailed a link to a survey in 2019. The survey included demographic details and a Discrete Choice Experiment examining influences on resident decisions to take a PCD off. RESULTS: One hundred seventy-five residents (40.4%) responded to the survey; 113 residents (26%) completed the survey. Positive feedback from attending physicians about taking PCDs off in the past had the greatest impact on respondents' decisions to take a PCD off, increasing the probability by 27.3%, followed by chief resident comments about the resident looking tired (16.6% increase), and having never heard their attendings comment about PCDs off as either positive or negative (13.9% increase). Factors that had the largest effect on decreasing the probability of taking a PCD were negative feedback about taking PCDs off (14.3% decrease), continuity of care concerns (10.8% decrease), and whether the resident was looking forward to an assignment (7.9% decrease). CONCLUSIONS: The most important influencer of residents' decisions to take a PCD off was related to feedback from their attending physicians, suggesting that compliance with WHRs can be improved by focusing on the residency program's safety culture.

Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Here, we examined parasites from 3,147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, we constructed a series of Poisson generalized linear mixed-effects models to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. We compared the model-predicted incidence with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (<10/1000/annual [‰]). When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence >10 ‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was <10 ‰, we found that many of the correlations between parasite genetics and incidence were reversed, which we hypothesize reflects the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets.

Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.Competing Interest StatementThe authors have declared no competing interest.

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Parasite genetic surveillance has the potential to play an important role in malaria control. We describe here an analysis of data from the first year of an ongoing, nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal, intended to provide actionable information for malaria control efforts. Looking for a good proxy for local malaria incidence, we found that the best predictor was the proportion of polygenomic infections (those with multiple genetically distinct parasites), although that relationship broke down at very low incidence. The proportion of closely related parasites in a site was more weakly correlated with incidence while the local genetic diversity was uninformative. Study of related parasites indicated their potential for discriminating local transmission patterns: two nearby study areas had similarly high fractions of relatives, but one area was dominated by clones and the other by outcrossed relatives. Throughout the country, most related parasites proved to belong to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci as well as at one novel locus, reflective of ongoing selection pressure. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

To understand genome evolution in a group of microbes, we need to know the timing of events such as duplications, deletions and horizontal transfers. A common approach is to perform a gene-tree / species-tree reconciliation. While a number of software packages perform this type of analysis, none are geared toward a complete reconstruction for all families in an entire clade. Here we describe an update to the xenoGI software package which allows users to perform such an analysis using the newly developed DTLOR (duplication-transfer-loss-origin-rearrangement) reconciliation model starting from genome sequences as input.

Introduction: The present study attempted to provide a proof-of-concept of usefulness of cluster analysis for identifying distinct and practically meaningful subgroups of drivers who differed in their perceived risk and frequency of texting while driving (TWD). Method: Using a hierarchical cluster analysis, which involves sequential steps in which individual cases are merged together one at a time based on their similarities, the study first attempted to identify distinct subgroups of drivers who differed in their perceived risk and frequency of TWD. To further evaluate the meaningfulness of the subgroups identified, the subgroups were compared in terms of levels of trait impulsivity and impulsive decision making for each gender. Results: The study identified the following three distinct subgroups: (a) drivers who perceive TWD as risky but frequently engage in TWD; (b) drivers who perceive TWD as risky and infrequently engage in TWD; and (c) drivers who perceive TWD as not so risky and frequently engage in TWD. The subgroup of male, but not female, drivers who perceive TWD as risky but frequently engage in TWD showed significantly higher levels of trait impulsivity, but not impulsive decision making, than the other two subgroups. Discussion: This is the first demonstration that drivers who frequently engage in TWD can be categorized into two distinct subgroups that differ in terms of the perceived risk of TWD. Practical applications: For drivers who perceived TWD as risky yet frequently engage in TWD, the present study suggests that different intervention strategies may be needed for each gender. © 2023 National Safety Council and Elsevier Ltd

In occupational safety and health, big data and analytics show promise for the prediction and prevention of workplace injuries. Advances in computing power and analytical methods have allowed companies to reveal insights from the “big” data that previously would have gone undetected. Despite the promise, occupational safety has lagged behind other industries, such as supply chain management and healthcare, in terms of exploiting the potential of analytics and much of the data collected by organizations goes unanalyzed. The purpose of the present paper is to argue for the broader application of establishment-level safety analytics. This is accomplished by defining the terms, describing previous research, outlining the necessary components required, and describing knowledge gaps and future directions. The knowledge gaps and future directions for research in establishment-level analytics are categorized into readiness for analytics, analytics methods, technology integration, data culture, and impact of analytics. © 2023

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Background: Attributable fractions (AF) of anemia are often used to understand the multifactorial etiologies of anemia, despite challenges interpreting them in cross-sectional studies. We aimed to compare different statistical approaches for estimating AF for anemia due to inflammation, malaria, and micronutrient deficiencies including iron, vitamin A, vitamin B12, and folate.

BACKGROUND: In the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain. OBJECTIVES: We describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings. METHODS: Cross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications. RESULTS: In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines. CONCLUSIONS: Where having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME), which sets the standards for residency training, instituted work-hour restrictions in 2003. Our purpose was to assess residents' perceptions of fatigue and local safety climate specific to these duty-hour restrictions. METHODS:  All residents (N=433) at one university were emailed a link to a survey in 2019. The survey included demographic details, on-call descriptors, an 18-point climate survey (CS), and the 33-point Chalder Fatigue Questionnaire (CFQ). The CS was adapted from a commonly used safety climate scale and intended to measure the respondent's perceptions of their program's attitudes and practices around resident duty-hour compliance. A Pearson correlational analysis was used to determine if there were associations between the variables. RESULTS:  Mean CS score was 12.89 (95% confidence interval, CI 12.32-13.46, N=164, 48.5%). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME duty-hour restrictions," where 57 (34.7%) disagreed or strongly disagreed. Mean CFQ score was 16.02 (95% CI 14.87-17.17, N=113, 26.1%). As the CS score improved, CFQ scores decreased indicating an inverse relationship between duty-hour climate and fatigue (r=-0.328, p<0.05). Having a protected post-call day off, and having either the Program Director, Chief Resident, or Senior Resident decide that a resident takes a post-call day off were all associated with higher CS scores.  Conclusion: We found that the CS had good internal consistency and evidence of construct validity. An inverse relationship between CS score and fatigue suggests that the level of fatigue is higher among residents in programs where residents perceived that ACGME duty-hour compliance was less important.

BACKGROUND: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data. METHODS: As part of the Botswana Combination Prevention Project, 20% of households in 30 villages were tested for HIV and followed from 2013 to 2018. A total of 12,610 participants were enrolled, 3596 tested HIV-positive at enrolment, and 147 participants acquired HIV during the trial. Extensive socio-demographic and behavioural data were collected from participants and next-generation sequences were generated for HIV-positive cases. We compared three groups of participants: (1) those previously known to be HIV-positive at enrolment (n = 2995); (2) those newly diagnosed at enrolment (n = 601) and (3) those who tested HIV-negative at enrolment but tested HIV-positive during follow-up (n = 147). We searched for differences in demographic and behavioural factors between known and newly diagnosed group using logistic regression. We also compared the topology of each group in HIV-1 phylogenies and used a genetic diversity-based algorithm to classify infections as recent (< 1 year) or chronic (≥ 1 year). RESULTS: Being male (aOR = 2.23) and younger than 35 years old (aOR = 8.08) was associated with undiagnosed HIV infection (p < 0.001), as was inconsistent condom use (aOR = 1.76). Women were more likely to have undiagnosed infections if they were married, educated, and tested frequently. For men, being divorced increased their risk. The genetic diversity-based algorithm classified most incident infections as recent (75.0%), but almost none of known infections (2.0%). The estimated proportion of recent infections among new diagnoses was 37.0% (p < 0.001). CONCLUSION: Our results indicate that those with undiagnosed infections are likely to be young men and women who do not use condoms consistently. Among women, several factors were predictive: being married, educated, and testing frequently increased risk. Men at risk were more difficult to delineate. A sizeable proportion of undiagnosed infections were recent based on a genetic diversity-based classifier. In the era of "test and treat all", pre-exposure prophylaxis may be prioritized towards individuals who self-identify or who can be identified using these predictors in order to halt onward transmission in time.

PURPOSE: Hospitals are important workplaces for nurses with many perceived barriers to healthy eating, but objective assessments are lacking. This study evaluated the healthfulness of hospital consumer food environments. DESIGN: Cross-sectional observational; Setting: South Carolina; Subjects: Cafeterias, vending machines (VM), and gift shops (GS) in hospitals of varying size, urbanization, and region. MEASURES: Using the Hospital Nutrition Environment Scan (HNES), primary outcomes of interest included availability, access, prices, and location of healthy foods in relation to nursing units. ANALYSIS: Descriptive and inferential statistics by independent samples t-test, ANOVA, Mann-Whitney U, χ2, or Fisher's exact test as appropriate. RESULTS: Thirty-one hospitals were observed from December 2019 to February 2020. Average composite HNES score (n = 28) was 46.3 ± 14.9 (-45 to 173 range), indicating sub-optimal food environments. Cafeterias (n = 31) scored an average of 30.9 ± 10.5 (-33 to 86 range). Average VM (n = 31) and GS (n = 28) scores were 11.6 ± 6.0 (-6 to 55 range) and 2.9 ± 4.0 (-6 to 32 range), respectively. Small hospitals (≤100 beds) had lower average cafeteria score (22.4 ± 10.3) than extra-large hospitals (≥500 beds; 42 ± 5.2, P < .01). Small hospitals also had lower composite HNES scores (34.4 ± 17.1) compared to extra-large hospitals (61.0 ± 14.4, P = .02). Data regarding availability, access, prices, and location were also reported. CONCLUSION: Due to abundant availability of unhealthy foods and beverages, hospital consumer food environments scored low on observations using the HNES, highlighting the opportunity to improve the healthfulness of facility offerings.

BACKGROUND: and Setting: The Botswana Combination Prevention Project (BCPP) demonstrated a 30% reduction in community HIV incidence through expanded HIV testing, enhanced linkage to care, and universal antiretroviral treatment and exceeded the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. We report rates and characteristics of incident HIV infections. METHODS: BCPP was a community-randomized controlled trial conducted in 30 rural/peri-urban Botswana communities from 2013 to 2017. Home-based and mobile HIV-testing campaigns were conducted in 15 intervention communities, with 39% of participants testing at least twice. We assessed the HIV incidence rate (IR; number of new HIV infections per 100 person-years (py) at risk) among repeat testers and risk factors with a Cox proportional hazards regression model. RESULTS: During 27,517py, 195 (women,79%) of 18,597 became HIV-infected (0.71/100py). Women had a higher IR (1.01/100py; 95% CI, 0.99 to 1.02) than men (0.34/100py; 95% CI, 0.33 to 0.35). The highest IRs were among women aged 16-24 years (1.87/100py) and men aged 25-34 years (0.56/100py). The lowest IRs were among those aged 35-64 years (women,0.41/100py; men,0.20/100py). Hazard of incident infection was highest among women aged 16-24 (HR=7.05). Sex and age were significantly associated with incidence (both P<0.0001). CONCLUSIONS: Despite an overall reduction in HIV incidence and approaching the UNAIDS 95-95-95 targets, high HIV incidence was observed in adolescent girls and young women. These findings highlight the need for additional prevention services [pre-exposure prophylaxis (PrEP), DREAMS] to achieve epidemic control in this subpopulation and increased efforts with men with undiagnosed HIV.

BACKGROUND: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision (VMMC) referrals increased coverage and decreased incidence over ∼29 months follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population. SETTING: Rural and peri-urban communities in Botswana. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model to estimate lifetime health impact and cost of 1) earlier ART initiation, and 2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio (ICER, US$/QALY) for CP vs. standard of care. RESULTS: In CP, 1,418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9,200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an ICER of $79 per QALY. CONCLUSIONS: Enhanced HIV testing, linkage, and early ART initiation improves life expectancy, reduces transmission, and can be cost-effective or cost-saving in settings like Botswana.

In this paper, we introduce discrete choice experiments (DCEs) and provide foundational knowledge on the topic. DCEs are one of the most popular methods within econometrics to study the distribution of choices within a population. DCEs are particularly useful when studying the effects of categorical variables on choice. Procedurally, a DCE involves recruiting a large sample of individuals exposed to a set of choice arrays. The factors that are suspected to affect choice are varied systematically across the choice arrays. Most commonly, DCE data are analyzed with a multinomial logit statistical model with a goal of determining the relative utility of each relevant factor. We also discuss DCEs in comparison with behavioral choice models, such as those based on the matching law, and we show an example of a DCE to illustrate how a DCE can be used to understand choice with behavioral, social, and organizational factors.

Police officers experience exposures associated with increased inflammation, such as the stress associated with shiftwork and poor-quality diet, both of which have been shown to affect sleep duration and quality. This study examined the longitudinal and cross-sectional effects of the Energy-density Dietary Inflammatory Index (E-DII™) on objectively and subjectively measured sleep among police officers. Data were derived from the Buffalo Cardio-Metabolic Occupational Police Stress Cohort (n = 464 at baseline), with longitudinal data collected from 2004 to 2019. A food frequency questionnaire obtained estimated dietary intake from which E-DII scores were calculated. Dependent variables were objectively (Micro Motion Logger Sleep Watch™) and subjectively (Pittsburgh Sleep Quality Index) measured sleep quality and quantity. The analyses included a series of linear mixed-effects models used to examine cross-sectional and longitudinal associations between the E-DII and sleep quantity and quality. Cross-sectionally, more pro-inflammatory diets were associated with higher wake-after-sleep-onset but improved subjective sleep quality. In models accounting for both longitudinal and cross-sectional effects, for every 1-unit increase in the E-DII scores over time (representing a pro-inflammatory change), wake-after-sleep-onset increased by nearly 1.4 min (p = 0.07). This result was driven by officers who primarily worked day shifts (β = 3.33, p = 0.01). Conversely, for every 1-unit increase in E-DII score, the Pittsburgh Sleep Quality Index global score improved. More pro-inflammatory diets were associated with increased wake-after-sleep-onset, an objective measure of sleep quality. Intervention studies to reduce dietary inflammatory potential may provide greater magnitude of effect for changes in sleep quality.

Retracing microbial emergence and spread is essential to understanding the evolution and 40 dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal 41 complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is 42 strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 43 isolates collected from 40 countries, since the first Lm isolation to the present day, to 44 define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 45 spread worldwide from North America following the Industrial Revolution through two 46 waves of expansion, coinciding with the transatlantic livestock trade in the second half of 47 the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then 48 firmly established at a local level, with limited inter-country spread. This study provides 49 an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute 50 to effective disease surveillance to reduce the burden of listeriosis.

BACKGROUND: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. METHODS: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression. RESULTS: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. CONCLUSIONS: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. CLINICAL TRIAL NUMBER: NCT01965470.