At-Home Versus Onsite COVID-19 School-based Testing: A Randomized Noninferiority Trial.

OBJECTIVES: Equitable access to coronavirus 2019 (COVID-19) screening is important to reduce transmission and maintain in-person learning for middle school communities, particularly in disadvantaged schools. Rapid antigen testing, and at-home testing in particular, could offer substantial advantages over onsite testing from a school district's perspective, but it is unknown if engagement in at-home testing can be initiated and sustained. We hypothesized that an at-home COVID-19 school testing program would be noninferior to an onsite school COVID-19 testing program with regard to school participation rates and adherence to a weekly screening testing schedule. METHODS: We enrolled 3 middle schools within a large, predominantly Latinx-serving, independent school district into a noninferiority trial from October 2021 to March 2022. Two schools were randomized to onsite and 1 school to at-home COVID-19 testing programs. All students and staff were eligible to participate. RESULTS: Over the 21-week trial, at-home weekly screening testing participation rates were not inferior to onsite testing. Similarly, adherence to the weekly testing schedule was not inferior in the at-home arm. Participants in the at-home testing arm were able to test more consistently during and before returning from school breaks than those in the onsite arm. CONCLUSIONS: Results support the noninferiority of at-home testing versus onsite testing both in terms of participation in testing and adherence to weekly testing. Implementation of at-home COVID-19 screening testing should be part of schools' routine COVID-19 prevention efforts nationwide; however, adequate support is essential to ensure participation and persistence in regular at-home testing.

A Psychometric Evaluation and a Framework Test of the HIV Stigma Mechanisms Scale Among a Population-Based Sample of Men and Women Living with HIV in Central Uganda.

HIV stigma is a critical barrier to HIV prevention and care. This study evaluates the psychometric properties of the HIV Stigma Mechanisms Scale (HIV-SMS) among people living with HIV (PLHIV) in central Uganda and tests the underlying framework. Using data from the PATH/Ekkubo study, (n = 804 PLHIV), we assessed the HIV-SMS' reliability and validity (face, content, construct, and convergent). We used multiple regression analyses to test the HIV-SMS' association with health and well-being outcomes. Findings revealed a more specific (5-factor) stigma structure than the original model, splitting anticipated and enacted stigmas into two subconstructs: family and healthcare workers (HW). The 5-factor model had high reliability (α = 0.92-0.98) and supported the convergent validity (r = 0.12-0.42, p < 0.01). The expected relationship between HIV stigma mechanisms and health outcomes was particularly strong for internalized stigma. Anticipated-family and enacted-family stigma mechanisms showed partial agreement with the hypothesized health outcomes. Anticipated-HW and enacted-HW mechanisms showed no significant association with health outcomes. The 5-factor HIV-SMS yielded a proper and nuanced measurement of HIV stigma in central Uganda, reflecting the importance of family-related stigma mechanisms and showing associations with health outcomes similar to and beyond the seminal study.

Prevalence and correlates of depressive symptoms, and points of intervention, in rural central Uganda: results from a cross-sectional population-based survey of women and men.

OBJECTIVES: The present study aimed to identify the prevalence and correlates of depressive symptoms and potential intervention points among women and men from a population-based sample in rural central Uganda. DESIGN: A cross-sectional study. SETTING: Four districts in rural Uganda. PARTICIPANTS: Women and men aged 15-59 residing in four districts in rural Uganda accepting home-based HIV testing who completed a baseline survey at the time of testing. PRIMARY OUTCOME MEASURES: Depressive symptoms measured by the 10-item Center for Epidemiological Studies Depression Scale using a cut-off score of 13 for significant depressive symptoms. RESULTS: Among a sample of 9609 women and 6059 men, 1415 (14.7%) women and 727 (12.0%) men met criteria for significant depressive symptoms. Having ever received mental health services was associated with lower odds of significant depressive symptoms (women: adjusted OR (adjOR)=0.32, 95% CI=0.22 to 0.47; men: adjOR=0.36, 95% CI=0.18 to 0.62). Having received outpatient (women: adjOR=3.64, 95% CI=3.14 to 4.22; men: adjOR=3.37, 95% CI=2.78 to 4.07) or inpatient (women: adjOR=5.44, 95% CI=4.24 to 6.97; men: adjOR=3.42, 95% CI=2.21 to 5.28) care in the prior 6 months was associated with greater odds of significant depressive symptoms. For women only, known HIV positive status (adjOR=1.37, 95% CI=1.05 to 1.77), and for men only, alcohol misuse (adjOR=1.38, 95% CI=1.12 to 1.70), were associated with increased odds of significant depressive symptoms. CONCLUSION: Our findings suggest that depression screening within outpatient and inpatient settings may help to identify people in need of mental health services. Routine screening in outpatient or inpatient clinics along with the implementation of evidence-based interventions could ultimately help close the mental health gap for depression in this and similar settings.

A note on point estimation and interval estimation of the relative treatment effect under a simple crossover design.

To increase power or reduce the number of patients needed for a parallel groups design, the crossover design has been often used to study treatments for noncurable chronic diseases. However, in the presence of carry-over effect caused by treatments, the commonly-used estimator which ignores the carry-over effect leads to a biased estimator for estimating the treatment effect difference. A two-stage test approach aimed to address carry-over effect proposed was found to be potentially misleading. In this paper, we propose a weighted average of the commonly-used estimator and an unbiased estimator that uses only the first period of the data. We derive an optimal weight that minimizes the mean squared error (MSE) and its modified estimator. We apply Monte Carlo simulation to evaluate the performance of the proposed estimators in a variety of situations. In the simulations, we examine the estimated MSE (EMSE), percentile interval length, and coverage probability calculated from the percentile intervals among considered estimators. Simulation results show that our proposed weighted average estimator and its modified estimator lead to smaller EMSEs on average comparing to the two commonly used estimators. The coverage probabilities using our proposed estimators are reasonably close to the nominal confidence level and the interval lengths are shorter comparing to the use of the unbiased estimator that uses only the first period of the data. We apply an example that was to evaluate the efficacy of two type of bronchodilators for asthma treatment to demonstrate the use of the proposed estimators.

Pilot randomised controlled trial of a patient navigation intervention to enhance engagement in the PrEP continuum among young Latino MSM: a protocol paper.

INTRODUCTION: Men who have sex with men (MSM) are one of the most at-risk group for contracting HIV in the USA. However, the HIV epidemic impacts some groups of MSM disproportionately. Latino MSM comprise 25.1% of new HIV infections among MSM between the ages of 13 and 29 years. The daily medication tenofovir/emtricitabine was approved by the Food and Drug Administration for pre-exposure prophylaxis (PrEP) in 2012 and has demonstrated strong efficacy in reducing HIV acquisition. METHODS AND ANALYSIS: Through extensive formative research, this study uses a pilot randomised controlled trial design and will examine the feasibility and acceptability of a patient navigation intervention designed to address multiple barriers to improve engagement in the PrEP continuum among 60 Latino MSM between the ages of 18 and 29 years. The patient navigation intervention will be compared with usual care plus written information to evaluate the feasibility and acceptability of the intervention and study methods and the intervention's potential in improving PrEP continuum behaviours. The results will be reviewed for preparation for a future full-scale efficacy trial. ETHICS AND DISSEMINATION: This study was approved by the institutional review board at San Diego State University and is registered at ClinicalTrials.gov. The intervention development process, plan and the results of this study will be shared through peer-reviewed journal publications, conference presentations and healthcare system and community presentations. REGISTRATION DETAILS: Registered under the National Institutes of Health's ClinicalTrials.gov (NCT04048382) on 7 August 2019 and approved by the San Diego State University (HS-2017-0187) institutional review board. This study began on 5 August 2019 and is estimated to continue through 31 March 2021. The clinical trial is in the pre-results stage.

Perceived HIV stigma and HIV testing among men and women in rural Uganda: a population-based study.

BACKGROUND: Stigma is a formidable social structural barrier to HIV testing, and yet the effect of stigma on HIV testing is rarely examined at the community level. We aimed to examine the geospatial relationships of perceived HIV stigma and HIV testing among men and women living in rural Uganda. METHODS: Women and men (aged ≥18 years or emancipated minor) residing in rural areas of Uganda who self-identified as HIV negative completed interviews that included measures of HIV testing history and how participants perceived HIV stigma. We used geospatial cluster analyses to identify areas of higher perceived stigma and lower perceived stigma and the geographical dispersion of these areas. We used Poisson regression models stratified by gender to test individual-level and community-level perceived stigma in relation to frequency of HIV testing in the previous 2 years. FINDINGS: Between Nov 25, 2015, and May 26, 2017, we interviewed 9740 participants (4359 [45%] men and 5381 [55%] women]), among whom 940 (9%) had never been tested for HIV, and among those who had been tested, 1131 (12%) had not been tested in the previous 2 years. Men (3134 [72%] of 4359) were less likely to have been tested in the past 2 years than women (4535 [84%] of 5381) were (p<0·001). We used Poisson regression models, reporting B coefficients, to test study hypotheses regarding the effects of individual-level and community-level stigma on HIV testing frequency counts. Multilevel modelling showed that women showed significant individual-level (B=-0·173, p<0·001) and community-level (B=-0·223, p<0·001) associations between lower stigma predicting higher rates of HIV testing. For men, lower individual-level perceived stigma was also associated with higher testing frequency (B=-0·030, p=0·018), whereas higher community-level perceived stigma was associated with higher testing frequency (B=0·077, p=0·008). INTERPRETATION: Our results suggest that perceived HIV stigma at the community level exerts a differential influence on testing for women and men. HIV testing campaigns that are targeted to men and women in rural Uganda will require gender tailoring to fit local contexts. FUNDING: US National Institute of Mental Health.

Efficacy of an enhanced linkage to HIV care intervention at improving linkage to HIV care and achieving viral suppression following home-based HIV testing in rural Uganda: study protocol for the Ekkubo/PATH cluster randomized controlled trial.

BACKGROUND: Though home-based human immunodeficiency virus (HIV) counseling and testing (HBHCT) is implemented in many sub-Saharan African countries as part of their HIV programs, linkage to HIV care remains a challenge. The purpose of this study is to test an intervention to enhance linkage to HIV care and improve HIV viral suppression among individuals testing HIV positive during HBHCT in rural Uganda. METHODS: The PATH (Providing Access To HIV Care)/Ekkubo Study is a cluster-randomized controlled trial which compares the efficacy of an enhanced linkage to HIV care intervention vs. standard-of-care (paper-based referrals) at achieving individual and population-level HIV viral suppression, and intermediate outcomes of linkage to care, receipt of opportunistic infection prophylaxis, and antiretroviral therapy initiation following HBHCT. Approximately 600 men and women aged 18-59 who test HIV positive during district-wide HBHCT in rural Uganda will be enrolled in this study. Villages (clusters) are pair matched by population size and then randomly assigned to the intervention or standard-of-care arm. Study teams visit households and participants complete a baseline questionnaire, receive HIV counseling and testing, and have blood drawn for HIV viral load and CD4 testing. At baseline, standard-of-care arm participants receive referrals to HIV care including a paper-based referral and then receive their CD4 results via home visit 2 weeks later. Intervention arm participants receive an intervention counseling session at baseline, up to three follow-up counseling sessions at home, and a booster session at the HIV clinic if they present for care. These sessions each last approximately 30 min and consist of counseling to help clients: identify and reduce barriers to HIV care engagement, disclose their HIV status, identify a treatment supporter, and overcome HIV-related stigma through links to social support resources in the community. Participants in both arms complete interviewer-administered questionnaires at six and 12 months follow-up, HIV viral load and CD4 testing at 12 months follow-up, and allow access to their medical records. DISCUSSION: The findings of this study can inform the integration of a potentially cost-effective approach to improving rates of linkage to care and HIV viral suppression in HBHCT. If effective, this intervention can improve treatment outcomes, reduce mortality, and through its effect on individual and population-level HIV viral load, and decrease HIV incidence. TRIAL REGISTRATION: NCT02545673.

Testing equality and interval estimation of the generalized odds ratio in ordinal data under a three-period crossover design.

The crossover design can be of use to save the number of patients or improve power of a parallel groups design in studying treatments to noncurable chronic diseases. We propose using the generalized odds ratio for paired sample data to measure the relative effects in ordinal data between treatments and between periods. We show that one can apply the commonly used asymptotic and exact test procedures for stratified analysis in epidemiology to test non-equality of treatments in ordinal data, as well as obtain asymptotic and exact interval estimators for the generalized odds ratio under a three-period crossover design. We further show that one can apply procedures for testing the homogeneity of the odds ratio under stratified sampling to examine whether there are treatment-by-period interactions. We use the data taken from a three-period crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea to illustrate the use of these test procedures and estimators proposed here.

Digitization of Electrocardiogram From Telemetry Prior to In-hospital Cardiac Arrest: A Pilot Study.

BACKGROUND: Analyzing telemetry electrocardiogram (ECG) data over an extended period is often time-consuming because digital records are not widely available at hospitals. Investigating trends and patterns in the ECG data could lead to establishing predictors that would shorten response time to in-hospital cardiac arrest (I-HCA). This study was conducted to validate a novel method of digitizing paper ECG tracings from telemetry systems in order to facilitate the use of heart rate as a diagnostic feature prior to I-HCA. METHODS: This multicenter study used telemetry to investigate full-disclosure ECG papers of 44 cardiovascular patients obtained within 1 hr of I-HCA with initial rhythms of pulseless electrical activity and asystole. Digital ECGs were available for seven of these patients. An algorithm to digitize the full-disclosure ECG papers was developed using the shortest path method. The heart rate was measured manually (averaging R-R intervals) for ECG papers and automatically for digitized and digital ECGs. RESULTS: Significant correlations were found between manual and automated measurements of digitized ECGs (p < .001) and between digitized and digital ECGs (p < .001). Bland-Altman methods showed bias = .001 s, SD = .0276 s, lower and upper 95% limits of agreement for digitized and digital ECGs = .055 and -.053 s, and percentage error = 0.22%. Root mean square (rms), percentage rms difference, and signal to noise ratio values were in acceptable ranges. CONCLUSION: The digitization method was validated. Digitized ECG provides an efficient and accurate way of measuring heart rate over an extended period of time.

Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes.

BACKGROUND: Dengue is one of the most aggressively expanding mosquito-transmitted viruses. The human burden approaches 400 million infections annually. Complex transmission dynamics pose challenges for predicting location, timing, and magnitude of risk; thus, models are needed to guide prevention strategies and policy development locally and globally. Weather regulates transmission-potential via its effects on vector dynamics. An important gap in understanding risk and roadblock in model development is an empirical perspective clarifying how weather impacts transmission in diverse ecological settings. We sought to determine if location, timing, and potential-intensity of transmission are systematically defined by weather. METHODOLOGY/PRINCIPAL FINDINGS: We developed a high-resolution empirical profile of the local weather-disease connection across Peru, a country with considerable ecological diversity. Applying 2-dimensional weather-space that pairs temperature versus humidity, we mapped local transmission-potential in weather-space by week during 1994-2012. A binary classification-tree was developed to test whether weather data could classify 1828 Peruvian districts as positive/negative for transmission and into ranks of transmission-potential with respect to observed disease. We show that transmission-potential is regulated by temperature-humidity coupling, enabling epidemics in a limited area of weather-space. Duration within a specific temperature range defines transmission-potential that is amplified exponentially in higher humidity. Dengue-positive districts were identified by mean temperature >22°C for 7+ weeks and minimum temperature >14°C for 33+ weeks annually with 95% sensitivity and specificity. In elevated-risk locations, seasonal peak-incidence occurred when mean temperature was 26-29°C, coincident with humidity at its local maximum; highest incidence when humidity >80%. We profile transmission-potential in weather-space for temperature-humidity ranging 0-38°C and 5-100% at 1°C x 2% resolution. CONCLUSIONS/SIGNIFICANCE: Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.

Electrocardiogram characteristics prior to in-hospital cardiac arrest.

Survival after in-hospital cardiac arrest (I-HCA) remains < 30 %. There is very limited literature exploring the electrocardiogram changes prior to I-HCA. The purpose of the study was to determine demographics and electrocardiographic predictors prior to I-HCA. A retrospective study was conducted among 39 cardiovascular subjects who had cardiopulmonary resuscitation from I-HCA with initial rhythms of pulseless electrical activity (PEA) and asystole. Demographics including medical history, ejection fraction, laboratory values, and medications were examined. Electrocardiogram (ECG) parameters from telemetry were studied to identify changes in heart rate, QRS duration and morphology, and time of occurrence and location of ST segment changes prior to I-HCA. Increased age was significantly associated with failure to survive to discharge (p < 0.05). Significant change was observed in heart rate including a downtrend of heart rate within 15 min prior to I-HCA (p < 0.05). There was a significant difference in heart rate and QRS duration during the last hour prior to I-HCA compared to the previous hours (p < 0.05). Inferior ECG leads showed the most significant changes in QRS morphology and ST segments prior to I-HCA (p < 0.05). Subjects with an initial rhythm of asystole demonstrated significantly greater ECG changes including QRS morphology and ST segment changes compared to the subjects with initial rhythms of PEA (p < 0.05). Diagnostic ECG trends can be identified prior to I-HCA due to PEA and asystole and can be further utilized for training a predictive machine learning model for I-HCA.

The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*.

OBJECTIVE: To determine if the selective vasopressin type 1a receptor agonist selepressin (FE 202158) is as effective as the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis. DESIGN: Prospective, randomized, controlled laboratory experiment. SETTING: University animal research facility. SUBJECTS: Forty-five chronically instrumented sheep. INTERVENTIONS: Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure fell by more than 10 mm Hg from baseline level, an additional continuous IV infusion of arginine vasopressin or selepressin was titrated to raise and maintain mean arterial pressure within no less than 10 mm Hg from baseline level. Effects of combination treatment of selepressin with the selective vasopressin V2 receptor agonist desmopressin were similarly investigated. MEASUREMENTS AND MAIN RESULTS: In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of fluid were retained over 24 hours; this fluid accumulation was partially reduced by arginine vasopressin and almost completely blocked by selepressin; and combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to arginine vasopressin treatment. CONCLUSIONS: Resuscitation with the selective vasopressin type 1a receptor agonist selepressin blocked vascular leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist arginine vasopressin because of its lack of agonist activity at the vasopressin V2 receptor.

Trends and factors associated with initial and recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections among HIV-infected persons: an 18-year study.

BACKGROUND: Factors associated with initial methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs) and their recurrence have not been fully elucidated among HIV-infected persons. METHODS: We retrospectively evaluated a large cohort of HIV-infected patients from 1993 to 2010 for culture-proven MRSA SSTIs. Separate logistic regression models evaluated factors associated with initial and recurrent infections. RESULTS: Of the 794 patients, 63 (8%) developed an initial infection (19.8 infections/1000 person years [PY]); risk factors included CD4 count <500 cells/mm(3) and HIV RNA level ≥400 copies/mL (P < .01), US Centers for Disease Control and Prevention (CDC) stage C versus A/B (P < .01), and injection drug use (IDU, P < .01). In all, 27% developed recurrence (206 infections/1000 PY); risk factors included hospital admission (P = .02). Minocycline for treatment of the initial infection was associated with an 80% decreased odds for recurrence (P = .03). CONCLUSION: HIV control and avoidance of IDU may be useful in reducing rates of MRSA SSTIs among HIV-infected persons.

Training, deployment preparation, and combat experiences of deployed health care personnel: key findings from deployed U.S. Army combat medics assigned to line units.

OBJECTIVE: To describe the perceptions of training and deployment preparation and combat experiences and exposures of U.S. Army combat medics. METHODS: Data were from the first year of a 3-year longitudinal study designed to assess the impact of combat on the behavioral health and resilience of 347 combat medics surveyed 3 to 6 months after returning from a 12-month deployment to Operation Enduring Freedom/Operation Iraqi Freedom theatre and assigned to brigade combat teams. RESULTS: Analyses indicated that combat medics may benefit from better preparation in types of shifts required during deployment, type and intensity of combat likely to be seen and experienced, more adequate training in the area of stress and mental health care management, and easier access to behavioral mental health care. CONCLUSIONS: The military has shown considerable progress in addressing and understanding the mental health care needs of Soldiers. However, challenges remain. Additional emphasis should be placed on reducing the stigma and barriers related to mental health care both in theatre and garrison and on developing an evidence-based, validated program for medics and other Soldiers to recognize stress and mental health issues on the battlefield. For medics, this should be from two perspectives-that of a combat Soldier and that of a medical provider.

Modeling continuous auxiliary covariate data in generalized linear mixed models using the kernel smoother.

Auxiliary covariate data are often collected in biomedical studies when the primary exposure variable is only assessed on a subset of the study subjects. In this study, we investigate a semiparametric-estimated likelihood estimation for the generalized linear mixed models (GLMM) in the presence of a continuous auxiliary variable. We use a kernel smoother to handle continuous auxiliary data. The method can be used to deal with missing or mismeasured covariate data problems in a variety of applications when an auxiliary variable is available and cluster sizes are not too small. Simulation study results show that the proposed method performs better than that which ignores the random effects in GLMM and that which only uses data in the validation data set. We illustrate the proposed method with a real data set from a recent environmental epidemiology study on the maternal serum 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene level in relationship to preterm births.