Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2) Among Healthcare Providers Prior to the Vaccine Era in an Integrated Midwestern Healthcare System

We performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antinucleocapsid IgG testing on 5,557 healthcare providers and found a seroprevalence of 3.9%. African Americans were more likely to test positive than Whites, and HCWs with household exposure and those working on COVID-19 cohorting units were more likely to test positive than their peers

Kidney disease in Uganda: a community based study.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Sub-Saharan Africa (SSA). The majority of studies on CKD in SSA have been conducted among HIV-infected populations and mainly from large health facilities. We determined the prevalence of CKD and its predictors among populations in communities in central Uganda. METHODS: A cross-sectional study was conducted in Wakiso district using multi-stage sampling. Data was collected on age, sex, socio-economic status, history of alcohol intake, diabetes mellitus, hypertension and smoking. Measurement of blood pressure, weight and height to determine body mass index (BMI) and investigations including HIV testing, fasting blood sugar, creatinine and urinalysis were conducted. Logistic regression was used to estimate the strength of the association between variables and the presence of CKD estimated using the Cockcroft Gault formula. RESULTS: A total of 955 participants aged 18-87 years were enrolled into the study. The median age was 31 years (Interquartile range 24-42) and majority (67%) were female. Up to 21.4% (204/955) had abnormal renal function with CKD stage 1 in 6.2% (59/955), stage 2 in 12.7% (121/955), stage 3 in 2.4% (23/955), CKD stage 4 in 0% and CKD stage 5 in 0.1% (1/995). Female gender OR 1.8 (95% Confidence Interval [CI] 1.2-2.8), age >30 years OR 2.2(95% CI 1.2-3.8) and high social economic status OR 2.1 (95% CI 1.3-3.6) were associated with increased risk of CKD while BMI > 25Kg/m2 was protective against CKD OR 0.1 (95% CI 0.04-0.2). Traditional risk factors such as HIV-infection, diabetes mellitus, smoking and alcohol intake were not found to be significantly associated with CKD. CONCLUSION: We found a high prevalence of kidney disease in central Uganda. Interestingly the traditional risk factors associated with CKD previously documented, were not associated with CKD

HIV-associated anemia after 96 weeks on therapy: determinants across age ranges in Uganda and Zimbabwe.

Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5 g/dl, 12-14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management

U.S. Physician-Scientist Workforce in the 21st Century: Recommendations to Attract and Sustain the Pipeline

The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort. It is through biomedical research that certain diseases have been eliminated, cures for others have been discovered, and medical procedures and therapies that save lives have been developed. Yet, the U.S. PS workforce has both declined and aged over the last several years. The resulting decreased inflow and outflow to the PS pipeline renders the system vulnerable to collapsing suddenly as the senior workforce retires. In November 2015, the Alliance for Academic Internal Medicine hosted a consensus conference on the PS workforce to address issues impacting academic medical schools, with input from early-career PSs based on their individual experiences and concerns. One of the goals of the conference was to identify current impediments in attracting and supporting PSs and to develop a new set of recommendations for sustaining the PS workforce in 2016 and beyond. This Perspective reports on the opportunities and factors identified at the conference and presents five recommendations designed to increase entry into the PS pipeline and nine recommendations designed to decrease attrition from the PS workflow

Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone

Objectives: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone. Patients and methods: We conducted a cross-sectional study of HIV-positive adults aged 18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database andWHO 2009mutation list. Results: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone. Conclusions: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.Xunta Galicia-Fondo Social Europeo | Ref. IN606A-2016/023Case Western Reserve University | Ref. NIH NIAID T32 AI07024Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional-FEDER | Ref. RD16/0025/002

Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial

Objective: Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low–income African countries. Methods: Setting:: HIV clinics in Uganda and Zimbabwe. Design:: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without. Results: A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV–1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis. Conclusions: Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy

A case study of a real-time evaluation of the risk of disease transmission associated with a failure to follow recommended sterilization procedures

Background Failures to follow recommendations for reprocessing of surgical instruments may place patients at risk for exposure to pathogenic microorganisms. When such failures occur, medical facilities often face considerable uncertainty and challenges in assessing the actual risks of disease transmission. Methods In 2011, staff at an Ohio hospital determined that surgical instruments inside a Steriset Container had inadvertently been autoclaved on a gravity cycle rather than on the recommended pre-vacuum cycle, potentially exposing 72 patients who underwent surgery with the instruments to risk of infection. To provide an assessment of the level of risk, we tested the effectiveness of the machine washer/disinfector step and of the sterilization process inside the Steriset Container on the gravity cycle for killing of Geobacillus stearothermophilus spores, Clostridium difficile spores, and methicillin-resistant Staphylococcus aureus (MRSA). Based on the test results, the risk of transmission of MRSA by the instruments was calculated and the risk of transmission of hepatitis B virus was estimated. Results The machine washer/disinfector consistently reduced MRSA recovery by a factor of 1:100,000. The sterilization process inside the Steriset Container consistently reduced MRSA concentrations by a factor of >1:10,000,000 and killed 105 C. difficile spores and 105 G. stearothermophilus spores. The risk of MRSA transmission due to the incident was calculated to be 1 in 100 trillion. Conclusions The risk for transmission of infection due to the failure to follow recommended sterilization processes was negligible based upon complete killing of G. stearothermophilus biological indicator spores, C. difficile spores, and MRSA under conditions that replicated the incident where proper procedures were not followed. Such real-time assessments of the risks associated with specific incidents may provide evidence-based information that can be used to inform decisions regarding disclosure of the incident to patients

Multihospital Outbreak of Clostridium difficile Infection, Cleveland, Ohio, USA

To determine whether a multihospital Clostridium difficile outbreak was associated with epidemic strains and whether use of particular fluoroquinolones was associated with increased infection rates, we cultured feces from C. difficile–infected patients. Use of fluoroquionolones with enhanced antianaerobic activity was not associated with increased infection rates

A potassium tert-butoxide and hydrosilane system for ultra-deep desulfurization of fuels

Hydrodesulfurization (HDS) is the process by which sulfur-containing impurities are removed from petroleum streams, typically using a heterogeneous, sulfided transition metal catalyst under high H_2 pressures and temperatures. Although generally effective, a major obstacle that remains is the desulfurization of highly refractory sulfur-containing heterocycles, such as 4,6-dimethyldibenzothiophene (4,6-Me_2DBT), which are naturally occurring in fossil fuels. Homogeneous HDS strategies using well-defined molecular catalysts have been designed to target these recalcitrant S-heterocycles; however, the formation of stable transition metal sulfide complexes following C–S bond activation has largely prevented catalytic turnover. Here we show that a robust potassium (K) alkoxide (O)/hydrosilane (Si)-based (‘KOSi’) system efficiently desulfurizes refractory sulfur heterocycles. Subjecting sulfur-rich diesel (that is, [S] ∼ 10,000 ppm) to KOSi conditions results in a fuel with [S] ∼ 2 ppm, surpassing ambitious future governmental regulatory goals set for fuel sulfur content in all countries. Fossil fuels contain naturally occurring organosulfur impurities, with quantities varying depending on the type of feedstock. These sulfur-containing organic small molecules poison catalytic converters and generate polluting sulfur dioxides when combusted. Hydrodesulfurization (HDS) is the industrial process by which sulfur impurities are removed from petroleum fractions prior to their use as fuels. Currently, HDS is performed by treating petroleum with H_2 at high pressures and temperatures (that is, 150–2,250 psi and 400 °C) over heterogeneous catalysts such as cobalt-doped molybdenum sulfide supported on alumina (that is, CoMoS_x∕γ-Al_2O_3; Fig. 1a). However, certain organosulfur species, in particular dibenzothiophenes alkylated at positions 4 and 6, are not efficiently removed. Homogeneous strategies employing sophisticated, well-defined transition metal complexes—including those based on platinum, nickel, tungsten, molybdenum, palladium, ruthenium, rhodium, iron, cobalt, and others—have been extensively investigated. While these studies have provided valuable mechanistic insights, several fundamental issues, such as the formation of stable organometallic S–M species upon C–S bond activation by the metal centre (Fig. 1b), generally restrict industrial implementation of such methods. Rare examples of desulfurization of dibenzothiophenes alkylated at the 4 and 6 positions by homogeneous transition metal catalysis utilized either Ni compounds in combination with superstoichiometric alkyl Grignard reagents or Ni or Co phosphoranimide complexes in the presence of superstoichiometric KH. These issues pose a formidable challenge for the development of new HDS methods. Moreover, increasingly strict governmental regulations require limiting the sulfur content in diesel fuel and gasoline (in the US: typically <15 and <30 ppm, respectively) as well as other fuels, rendering the development of new powerful HDS methods a primary global concern. In 2013, Grubbs and co-workers reported the KO^tBu mediated cleavage of aryl C–O bonds in lignin models in the absence of transition metals using hydrosilanes. Careful inductively coupled plasma mass spectrometry (ICP-MS) analyses of the reagents and reaction mixtures ruled out catalysis with transition metals. We thus became interested in extending this method to sulfur heterocycles of relevance in oil and gas refining applications. Herein, we report that the robust KOtBu/silane-based (that is, KOSi) system is a powerful and effective homogeneous HDS method, which desulfurizes HDS-resistant dibenzothiophenes in good yield and reduces the sulfur content in diesel fuel to remarkably low levels (Fig. 1c)