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Efforts to end the HIV and hepatitis C virus (HCV) epidemics begin with ascertainment of a person's infection status through screening. Despite its importance as a site of testing, missed opportunities for screening in the Emergency Department (ED) are common. We describe the impact of implementing an individualized provider feedback intervention on HIV and HCV testing in a quaternary ED. We conducted an interrupted time series analysis to evaluate the impact of the intervention on weekly HIV and HCV screening in an observational cohort of patients seeking care in the ED. The intervention included a physician champion individualized feedback with peer comparisons to all providers in the ED and an existing HIV/HCV testing and response team. Data were abstracted from the electronic medical record (EMR) for 30 weeks before, during, and after implementing the intervention. We used Poisson regression analysis to estimate changes in the weekly counts and rates of HIV and HCV testing. The incidence rate ratios (IRRs) of HIV testing were 1.94 [95% confidence interval (CI) 1.85–2.04] and 1.38 (95% CI 1.31–1.45) times higher for the intervention and post-intervention period compared with the pre-intervention period. The IRRs of HCV testing was 6.96 (95% CI 6.40–7.58) and 4.70 (95% CI 4.31–5.13) for the intervention and post-intervention periods. There were no meaningful differences in demographic characteristics during the observation period. The intervention meaningfully increased HIV and HCV testing volume and positive case detection, including testing in high-risk groups like young adults and individuals without prior testing. Although diminished, the intervention effect sustained in the 30-week period following implementation.

Background and Aims Clostridioides difficile infection (CDI) is associated with a range of outcomes and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. Methods Eosinopenia was defined as 0 eosinophils/uL on the soonest peripheral blood draw within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of three large, unaffiliated hospital networks, tested positive for CDI by stool PCR and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. Results There were 4,518 unique hospitalized adults with CDI included (2,142 derivation cohort and 2,376 validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts respectively. In the validation cohort, the factors most strongly associated with death were eosinopenia [adjusted OR (aOR) 2.49, 95% CI 1.77-3.50], albumin 1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A six variable clinical prediction model was developed that improved upon existing classification schemes for CDI severity (AUROC of 0.75 vs. 0.68). Conclusions Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Objectives: The objectives of the study were to evaluate the benefit of awake prone positioning in COVID-19 patients hospitalized at Eka Kotebe General Hospital, Addis Ababa, Ethiopia. Materials and Methods: Consecutive patients with COVID-19 who require supplemental oxygen to maintain oxygen saturation of ≥90% during the month of October 2020 were enrolled. Structured questionnaires were employed to collect data. Admission oxygen saturation was recorded for each patient before and after their first proning session. Analysis of descriptive and comparison statistics was done using SPSS version 25. Results: A total of 61 patients were included in the study. The mean age (+SD) for the cohort was 55.4 (+16.9) years. The average duration of proning was 5+2.5 h/session and 8+6 h/day. The average oxygen saturation before proning was 89% (SD 5.2) and 93% (SD 2.8) 1 h after proning (P < 0.001); supplemental oxygen requirements significantly decreased with prone ventilation, before proning: FiO2 0.33 (+0.14) versus 1 h after prone ventilation: FiO2 0.31 (+0.13) (P < 0.001). Oxygen improvement with prone ventilation was not associated with duration of illness or total prone position hours. When assessed at 28 days after admission, 55.7% (n = 34) had been discharged home, 1.6% (n = 1) had died, and 42.6 (n = 26) were still hospitalized. Conclusion: Awake prone positioning demonstrated improved oxygen saturation in our oxygen requiring COVID-19 patients. Even though further studies are needed to support causality and determine the effect of proning on disease severity and mortality, early institution of prone ventilation in appropriate oxygen requiring COVID-19 patients should be encouraged.

RATIONALE: There is accumulating evidence that higher-than-standard doses of isoniazid are effective against low-to-intermediate–level isoniazid-resistant strains of Mycobacterium tuberculosis, but the optimal dose remains unknown. OBJECTIVES: To characterize the association between isoniazid pharmacokinetics (standard or high dose) and early bactericidal activity against M. tuberculosis (drug sensitive and inhA mutated) and N-acetyltransferase 2 status. METHODS: ACTG (AIDS Clinical Trial Group) A5312/INHindsight is a 7-day early bactericidal activity study with isoniazid at a normal dose (5 mg/kg) for patients with drug-sensitive bacteria and 5, 10, and 15 mg/kg doses for patients with inhA mutants. Participants with pulmonary tuberculosis received daily isoniazid monotherapy and collected sputum daily. Colony-forming units (cfu) on solid culture and time to positivity in liquid culture were jointly analyzed using nonlinear mixed-effects modeling. MEASUREMENTS AND MAIN RESULTS: Fifty-nine adults were included in this analysis. A decline in sputum cfu was described by a one-compartment model, whereas an exponential bacterial growth model was used to interpret time-to-positivity data. The model found that bacterial kill is modulated by isoniazid concentration using an effect compartment and a sigmoidal Emax relationship (a model linking the drug concentration to the observed effect). The model predicted lower potency but similar maximum kill of isoniazid against inhA-mutated compared with drug-sensitive isolates. Based on simulations from the pharmacokinetics-pharmacodynamics model, to achieve a drop in bacterial load comparable to 5 mg/kg against drug-sensitive tuberculosis, 10- and 15-mg/kg doses are necessary against inhA-mutated isolates in slow and intermediate N-acetyltransferase 2 acetylators, respectively. Fast acetylators underperformed even at 15 mg/kg. CONCLUSIONS: Dosing of isoniazid based on N-acetyltransferase 2 acetylator status may help patients attain effective exposures against inhA-mutated isolates. Clinical trial registered with www.clinicaltrials.gov (NCT01936831).

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6-63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non-alcohol-associated fatty liver disease, 23% alcohol-associated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End-Stage Liver Disease-sodium scores were 27.2 kg/m