Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.

Low concordance between CTPA and echocardiography in identification of right ventricular strain in PERT patients with acute pulmonary embolism.

PURPOSE: Right ventricular strain (RVS) is used to risk stratify patients with acute pulmonary embolism (PE) and influence treatment decisions. Guidelines suggest that either computed tomography pulmonary angiography (CTPA) or transthoracic echocardiography (TTE) can be used to assess RVS. We sought to determine how often CTPA and TTE yield discordant results and to assess the test characteristics of CTPA compared to TTE. METHODS: We analyzed data from a single-center registry of PE cases severe enough to warrant activation of the hospital's Pulmonary Embolism Response Team (PERT). We defined RVS as a right ventricular to left ventricular ratio (RV/LV) ≥ 1 or radiologist's interpretation of RVS on CTPA or as the presence of either RV dilation, hypokinesis, or septal bowing on TTE. RESULTS: We included 554 patients in our analysis, of whom 333 (60%) had concordant RVS findings on CTPA and TTE. Using TTE as the reference standard, CTPA had a sensitivity of 95% (95% CI 92-97%) and a specificity of 4% (95% CI 2-8%) for identifying RVS. CONCLUSIONS: In a selected population of patients with acute PE for which PERT was activated, CTPA is highly sensitive but not specific for the detection of RVS when compared to TTE.

COVID-19 Seroprevalence in ED Health Care Professionals Study: A Cross-Sectional Study.

INTRODUCTION: ED health care professionals are at the frontline of evaluation and management of patients with acute, and often undifferentiated, illness. During the initial phase of the SARS-CoV-2 outbreak, there were concerns that ED health care professionals may have been at increased risk of exposure to SARS-CoV-2 due to difficulty in early identification of patients. This study assessed the seroprevalence of SARS-CoV-2 antibodies among ED health care professionals without confirmed history of COVID-19 infection at a quaternary academic medical center. METHODS: This study used a cross-sectional design. An ED health care professional was deemed eligible if they had worked at least 4 shifts in the adult emergency department from April 1, 2020, through May 31, 2020, were asymptomatic on the day of blood draw, and were not known to have had prior documented COVID-19 infection. The study period was December 17, 2020, to January 27, 2021. Eligible participants completed a questionnaire and had a blood sample drawn. Samples were run on the Roche Cobas Elecsys Anti-SARS-CoV-2 antibody assay. RESULTS: Of 103 health care professionals (16 attending physicians, 4 emergency residents, 16 advanced practice professionals, and 67 full-time emergency nurses), only 3 (2.9%; exact 95% CI, 0.6%-8.3%) were seropositive for SARS-CoV-2 antibodies. DISCUSSION: At this quaternary academic medical center, among those who volunteered to take an antibody test, there was a low seroprevalence of SARS-CoV-2 antibodies among ED clinicians who were asymptomatic at the time of blood draw and not known to have had prior COVID-19 infection.

'Not all fevers are malaria': a mixed methods study of non-malarial fever management in rural southern Malawi.

INTRODUCTION: With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making. METHODS: A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5ºC or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication. RESULTS: In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions. CONCLUSION: Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

The Cedar Project: mortality among young Indigenous people who use drugs in British Columbia.

BACKGROUND: Young Indigenous people, particularly those involved in the child welfare system, those entrenched in substance use and those living with HIV or hepatitis C, are dying prematurely. We report mortality rates among young Indigenous people who use drugs in British Columbia and explore predictors of mortality over time. METHODS: We analyzed data collected every 6 months between 2003 and 2014 by the Cedar Project, a prospective cohort study involving young Indigenous people who use illicit drugs in Vancouver and Prince George, BC. We calculated age-standardized mortality ratios using Indigenous and Canadian reference populations. We identified predictors of mortality using time-dependent Cox proportional hazard regression. RESULTS: Among 610 participants, 40 died between 2003 and 2014, yielding a mortality rate of 670 per 100 000 person-years. Young Indigenous people who used drugs were 12.9 (95% confidence interval [CI] 9.2-17.5) times more likely to die than all Canadians the same age and were 7.8 (95% CI 5.6-10.6) times more likely to die than Indigenous people with Status in BC. Young women and those using drugs by injection were most affected. The leading causes of death were overdose (n = 15 [38%]), illness (n = 11 [28%]) and suicide (n = 5 [12%]). Predictors of mortality included having hepatitis C at baseline (adjusted hazard ratio [HR] 2.76, 95% CI 1.47-5.16), previous attempted suicide (adjusted HR 1.88, 95% CI 1.01-3.50) and recent overdose (adjusted HR 2.85, 95% CI 1.00-8.09). INTERPRETATION: Young Indigenous people using drugs in BC are dying at an alarming rate, particularly young women and those using injection drugs. These deaths likely reflect complex intersections of historical and present-day injustices, substance use and barriers to care.

The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile.

BACKGROUND: Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. OBJECTIVES: We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. METHODS: Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. RESULTS: Adults with both a BMI above the 90th percentile (>33.9kg/m2) and arsenic water concentrations ≥11µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV1/FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV1 alone or in ever-smokers. CONCLUSIONS: This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease.

The Alcohol Use Disorders Identification Test (AUDIT): Exploring the Factor Structure and Cutoff Thresholds in a Representative Post-Conflict Population in Northern Uganda.

AIMS: Despite increased use of the Alcohol Use Disorders Identification Test (AUDIT) in sub-Saharan Africa, few studies have assessed its underlying conceptual framework, and none have done so in post-conflict settings. Further, significant inconsistencies exist between definitions used for problematic consumption. Such is the case in Uganda, facing one of the highest per-capita alcohol consumption levels regionally, which is thought to be hindering rebuilding in the North after two decades of civil war. This study explores the impact of varying designation cutoff thresholds in the AUDIT as well as its conceptual factor structure in a representative sample of the population. METHODS: In all, 1720 Cango Lyec Project participants completed socio-economic and mental health questionnaires, provided blood samples and took the AUDIT. Participant characteristics and consumption designations were compared at AUDIT summary score thresholds of ≥3, ≥5 and ≥8. Confirmatory factor analyses (CFA) explored one-, two- and three-factor level models overall and by sex with relative and absolute fit indicators. RESULTS: There were no significant differences in participant demographic characteristics between thresholds. At higher cutoffs, the test increased in specificity to identify those with hazardous drinking, disordered drinking and suffering from alcohol-related harms. All conceptual models indicated good fit, with three-factor models superior overall and within both sexes. CONCLUSION: In Northern Uganda, a three-factor AUDIT model best explores alcohol use in the population and is appropriate for use in both sexes. Lower cutoff thresholds are recommended to identify those with potentially disordered drinking to best plan effective interventions and treatments. SHORT SUMMARY: A CFA of the AUDIT showed good fit for one-, two, and three-factor models overall and by sex in a representative sample in post-conflict Northern Uganda. A three-plus total AUDIT cutoff score is suggested to screen for hazardous drinking in this or similar populations.

The Outpatient Treatment of Venous Thromboembolism: Operational Impact and the Role of Novel Anticoagulants.

Pulmonary embolism (PE) and venous thromboembolism (VTE) are common diagnoses in the emergency department (ED), with significant potential morbidity and mortality. As a result, historically nearly all patients with PE have been admitted to the hospital for observation and treatment. In recent years, the ability to rapidly and accurately risk stratify patients with VTE according to their risk of short-term clinical deterioration has supported outpatient treatment, and non-vitamin K antagonist oral anticoagulants (NOACs) have further facilitated this approach. This review details the historical context and operational impact of managing VTE in the outpatient setting, describes a model for outpatient management of VTE, and suggests potential areas of further inquiry.

"The Cango Lyec Project - Healing the Elephant": HIV related vulnerabilities of post-conflict affected populations aged 13-49 years living in three Mid-Northern Uganda districts.

BACKGROUND: The protracted war between the Government of Uganda and the Lord's Resistance Army in Northern Uganda (1996-2006) resulted in widespread atrocities, destruction of health infrastructure and services, weakening the social and economic fabric of the affected populations, internal displacement and death. Despite grave concerns that increased spread of HIV/AIDS may be devastating to post conflict Northern Uganda, empirical epidemiological data describing the legacy of the war on HIV infection are scarce. METHODS: The 'Cango Lyec' Project is an open cohort study involving conflict-affected populations living in three districts of Gulu, Nwoya and Amuru in mid-northern Uganda. Between November 2011 and July 2012, 8 study communities randomly selected out of 32, were mapped and house-to-house census conducted to enumerate the entire community population. Consenting participants aged 13-49 years were enrolled and interviewer-administered data were collected on trauma, depression and socio-demographic-behavioural characteristics, in the local Luo language. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression was used to determine factors associated with HIV prevalence at baseline. RESULTS: A total of 2954 participants were eligible, of whom 2449 were enrolled. Among 2388 participants with known HIV status, HIV prevalence was 12.2% (95%CI: 10.8-13.8), higher in females (14.6%) than males (8.5%, p < 0.001), higher in Gulu (15.2%) than Nwoya (11.6%, p < 0.001) and Amuru (7.5%, p = 0.006) districts. In this post-conflict period, HIV infection was significantly associated with war trauma experiences (Adj. OR = 2.50; 95%CI: 1.31-4.79), the psychiatric problems of PTSD (Adj. OR = 1.44; 95%CI: 1.06-1.96), Major Depressive Disorder (Adj. OR = 1.89; 95%CI: 1.28-2.80) and suicidal ideation (Adj. OR = 1.87; 95%CI: 1.34-2.61). Other HIV related vulnerabilities included older age, being married, separated, divorced or widowed, residing in an urban district, ulcerative sexually transmitted infections, and staying in a female headed household. There was no evidence in this study to suggest that people with a history of abduction were more likely to be HIV positive. CONCLUSIONS: HIV prevalence in this post conflict-affected population is high and is significantly associated with age, trauma, depression, history of ulcerative STIs, and residing in more urban districts. Evidence-based HIV/STI prevention programs and culturally safe, gender and trauma-informed are urgently needed.

Identifying patients with problematic drug use in the emergency department: results of a multisite study.

STUDY OBJECTIVE: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment. METHODS: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use. RESULTS: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score ≥ 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use. CONCLUSION: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs.

Evaluating a clinical mentorship intervention on maternal and neonatal complications in primary health facilities in Blantyre district, Malawi: A longitudinal analysis of the Global Action in Nursing program.

BACKGROUND: While Malawi has made great strides increasing the number of facility-based births, maternal and neonatal mortality remains high. An intervention started in 2019 provided short-course training followed by year-long longitudinal bedside mentorship for nurse midwives at seven health facilities in Blantyre district. The intervention was initiated following invitation from the district to improve outcomes for patients during childbirth. This study examined the impact of the intervention on the reporting of obstetric and neonatal complications and related care. METHODS: Patient level data were collected from the District Health Information System 2 database from intervention and non-intervention facilities. Bivariate analysis explored the impact of longitudinal bedside mentorship on select District Health Information System 2 variables at six-month intervals. Outcomes were then analyzed using nonlinear quantile mixed models to better account for the impact of time and clustering at the facility level. RESULTS: Significant changes were found in the reporting of obstetric and neonatal complications over time at intervention facilities compared to non-intervention facilities. Intervention facilities showed statistically significant increases in the reporting of prolonged labor, pre/eclampsia, fetal distress, retained placenta, and premature labor. There was also a statistically significant decrease in the reporting of no complications in the multivariate model (95%CI: -0.8 to -0.2). In both the bivariate and multivariate models, the reporting of 'None' significantly decreased (0.8 % median), while the reporting of prematurity (0.2 % median) and asphyxia (0.3 % median) both significantly increased. The missingness of data at intervention facilities decreased to almost zero compared to non-intervention facilities. DISCUSSION: The increase in reported maternal and neonatal complications suggests improved early identification of complications at the facility level. The improved accuracy of patient data from intervention facilities shows the impact mentorship has on data quality which is crucial for the allocation of resources. By highlighting the apparent dose-response relationship of longitudinal bedside mentorship, this study will inform the broader use of mentorship in training programs. Future research is needed to explore the impact of longitudinal mentorship on quality of care.

Exploring the impact of COVID-19 on reported maternal and neonatal complications and access to maternal health care in five government health facilities in Blantyre, Malawi.

BACKGROUND: There is a dearth of studies assessing the effects of SARS-CoV-2 on the healthcare system and access to care, especially in lower- and middle-income countries such as Malawi. We aimed to assess the impacts of COVID-19 on reported maternal and neonatal complications as well as potential changes in maternal care access to care among five primary care health facilities in Blantyre, Malawi. METHODS: This retrospective cohort study assessed maternal and neonatal register data from five participating health centers in Blantyre, Malawi using the Malawi District Health Information Software 2 (DHIS2) to compare outcomes from 15 months before COVID-19 emerged, defined as the pre-Covid period (January 2019 -March 2020) with nine months after COVID-19 (April 2020 -December 2020). RESULTS: There was a significant decrease in reported use of vacuum extraction, which went from <0.01%in the pre-COVID period to 0% in the COVID period (p = 0.01). The proportion of births reporting fetal distress almost tripled from 0.46% to 1.36% (p = 0.001) during the COVID-19 period. Additionally, reported anticonvulsant use significantly increased from 0.01% to 1.2% (p<0.01), and antibiotic use significantly increased from 0.45% to 1.6% (p = 0.01). Asphyxia was the only significant neonatal complication variable reported, increasing from 2.80% to 3.45% (p = 0.01). CONCLUSION: Our findings suggest that significant outcomes were mainly due to the indirect effects of COVID-19 rather than the virus itself. Based on our findings and the contextual qualitative interviews with two Malawian expert midwives, we concluded that mothers may have been affected more due to understaffing and shortage of skilled personnel in the study health facilities. Therefore, the development of highly skilled health workers may contribute to better outcomes, along with adequate staffing and a streamlined referral process.

Water and war: The effect of functioning chlorinated water stations in reducing waterborne diseases during conflict in northwest Syria, 2017-2021.

Since 2011, Syria has been engulfed in a complex conflict marked by both targeted and indiscriminate attacks on civilians and civilian infrastructure. Water infrastructure has been continuously targeted, exacerbating problems with contamination of and access to clean adequate drinking water, and increasing the risk of waterborne diseases. We aimed to determine whether having access to more functional and chlorinated water stations is associated with a reduced risk of waterborne disease in northwest Syria. We examined the effect of functioning chlorinated water stations on the incidence of waterborne disease in 10 districts of Northwest Syria between January 1, 2017, and June 30, 2021, using weekly reported disease surveillance data and data from a water, sanitation, and hygiene (WASH) system evaluation program of the Assistance Coordination Unit (ACU). We ran eight negative binomial models to examine the association between functioning chlorinated water stations and the incidence of four of the five waterborne diseases: acute bloody diarrhea (ABD), acute other diarrhea (AOD), acute jaundice syndrome (AJS), and severe typhoid fever (STF). Dose-response models were used to investigate how the incidence of disease can theoretically be reduced as functioning and chlorinated water stations strategically increase. Compared to areas with lower quintiles of functioning and chlorinated water stations, the rates of the four waterborne diseases were lower in areas with higher quintiles of functioning and chlorinated water stations. Exposure to functioning water stations had a stronger association with lower rates of waterborne diseases than exposure to chlorinated water stations. Dose-response models demonstrate a potential for curbing the incidence of acute diarrhea and acute jaundice syndrome. The results of this study provide an understanding of the effects of water station functionality and chlorination in conflict settings. These findings support greater prioritization of WASH activities in countries experiencing violence against civilian infrastructure.

Assessing Combined Longitudinal Mentorship and Skills Training on Select Maternal and Neonatal Outcomes in Rural and Urban Health Facilities in Malawi.

INTRODUCTION: Despite successful efforts to improve clinical access and skilled birth attendance in Malawi, it still faces high rates of maternal and neonatal mortality. In 2017, the UCSF-GAIN partnership began a nurse-midwifery clinical education and longitudinal mentorship program. While it has received positive reviews, it is unclear whether routinely collected indicators can assess such a program's impact. METHOD: A longitudinal review of the Malawian DHIS2 database explored variables associated with maternal and newborn care and outcomes before and after the intervention. Data were analyzed using generalized estimating equations (GEE) to account for facility-level correlations over time. RESULTS: Quality issues with DHIS2 data were identified. Significant changes potentially associated with the GAIN intervention were noted. DISCUSSION: The GAIN approach appears to be associated with positive trends in maternal and neonatal care. National summary databases are problematic, however, for evaluating targeted interventions and the provision of care to specific outcomes.

Evaluating the Impact of Language Concordance on Coronavirus Disease 2019 Contact Tracing Outcomes Among Spanish-Speaking Adults in San Francisco Between June and November 2020.

We evaluated the impact of language concordance-clinician or public health worker fluency in a patient's primary language-on coronavirus disease 2019 (COVID-19) contact tracing outcomes among 2668 Spanish-speaking adults in San Francisco. Language concordance was associated with 20% greater odds of COVID-19 testing and 53% greater odds of support service referrals.

Risk Factors Predicting Cellulitis Diagnosis in a Prospective Cohort Undergoing Dermatology Consultation in the Emergency Department.

Cellulitis is an infection of the skin and skin-associated structures with many clinical mimickers known collectively as pseudocellulitis. Dermatology or infectious disease consultation is considered the gold standard for diagnosis. We evaluated a prospective cohort of adult patients presenting to the emergency department (ED) with concern for lower extremity cellulitis who received dermatology consultation with conferral of a final diagnosis. Possible risk factors independently associated with cellulitis diagnosis (P<.1) were included in a logistic regression model for prediction of cellulitis diagnosis. Factors having odds ratios with a confidence interval excluding 1 were identified as significant independent predictors. The study identified factors that should be considered in evaluation of patients with suspected uncomplicated lower extremity cellulitis.