The limit to evolutionary rescue depends on ploidy in yeast exposed to nystatin.

The number of copies of each chromosome, or ploidy, of an organism is a major genomic factor affecting adaptation. We set out to determine how ploidy can impact the outcome of evolution, as well as the likelihood of evolutionary rescue, using short-term experiments with yeast (Saccharomyces cerevisiae) in a high concentration of the fungicide nystatin. In similar experiments using haploid yeast, the genetic changes underlying evolutionary rescue were highly repeatable, with all rescued lines containing a single mutation in the ergosterol biosynthetic pathway. All of these beneficial mutations were recessive, which led to the expectation that diploids would find alternative genetic routes to adaptation. To test this, we repeated the experiment using both haploid and diploid strains and found that diploid populations did not evolve resistance. Although diploids are able to adapt at the same rate as haploids to a lower, not fully inhibitory, concentration of nystatin, the present study suggests that diploids are limited in their ability to adapt to an inhibitory concentration of nystatin, while haploids may undergo evolutionary rescue. These results demonstrate that ploidy can tip the balance between adaptation and extinction when organisms face an extreme environmental change.

High Hepatitis C Cure Rates Among Patients With Alcohol Use at a Safety-Net Hepatitis C Clinic.

OBJECTIVES: We set out to examine several aspects of the relationship between alcohol use and hepatitis C virus (HCV) among a cohort of patients treated at an HCV clinic within a safety net hospital. We examined (1) the prevalence of alcohol use among patients treated for HCV, (2) the likelihood of being started on treatment among patients who reported drinking alcohol compared with those who did not, and (3) the associations between alcohol use and HCV cure. METHODS: We performed a retrospective chart abstraction study using data from the Grady Liver Clinic, a specialty HCV clinic colocated in Grady Memorial Hospital's primary care clinic and run by general internists. RESULTS: Nine hundred fifty-four patients were included. The sustained virologic response rate among those with 12-week posttreatment measurement was 99.2%, with only 5 patients experiencing virologic failure. None of the alcohol use indicators significantly impacted sustained virologic response or loss to follow-up. Estimates of alcohol use ranged from 28.9% (by International Classification of Diseases, Tenth Revision, code) to 48.9% (clinician documentation). Treatment initiation rates were the same among those who did and did not report alcohol use. CONCLUSIONS: Alcohol use was not associated with decreased HCV cure rates. Our findings validate the inclusion of patients with alcohol use in HCV treatment programs.

A contactless cure: Leveraging telehealth to improve hepatitis C treatment at a safety-net hospital.

Hepatitis C virus (HCV) causes significant mortality worldwide. HCV is highly curable but access to care is limited for many patients. The Grady Liver Clinic (GLC), a primary care-based HCV clinic, utilizes a multidisciplinary team to provide comprehensive care for a medically underserved patient population in Atlanta, Georgia. The GLC added a telehealth option for HCV treatment at the start of the COVID-19 pandemic. We describe the outcomes of utilizing telehealth in this population. We performed a retrospective chart review of patients who initiated HCV treatment from March 2019 to February 2020 (pre-pandemic) and March 2020 to February 2021 (pandemic). Charts were abstracted for patient demographics and characteristics, treatment regimen, and treatment outcomes. Our primary outcome was HCV cure rate of the pre-pandemic compared to the pandemic cohorts and within the different pandemic cohort visit types. We performed an intention-to-treat (ITT) analysis for all patients who took at least one dose of a direct-acting antiviral (DAA) regardless of therapy completion, and a per-protocol (PP) analysis of those who completed treatment and were tested for HCV cure. SVR12 rates were >95% on ITT analysis, with no significant difference between pre-pandemic and pandemic cohorts. There was also no significant difference within the pandemic group when treatment was provided traditionally, via telehealth, or via a hybrid of these. Our findings support the use of telehealth as a tool to expand access to HCV treatment in a medically underserved patient population.

Large-Scale, Primary Care-Based Hepatitis C Treatment in an Urban, Medically Underserved Patient Population.

Hepatitis C virus (HCV) infection is a critical public health concern in the United States. HCV is highly curable, but access to care is limited for many patients. Primary care models can expand access to HCV care. The Grady Liver Clinic (GLC) is a primary care-based HCV clinic founded in 2002. During 20 years, using a multidisciplinary team, the GLC expanded its operations in response to advances in HCV screening and treatment. We describe the clinic model, patient population, and treatment outcomes of the clinic from 2015 through 2019. During this period, 2689 patients were seen in the GLC, and 77% (n = 2083) initiated treatment. Eighty-five percent (1779 of 2083) of patients who started treatment completed treatment and were tested for cure, and 1723 (83% of the total treated cohort, 97% of those tested for cure) were cured. Building on a successful primary care-based treatment model, the GLC dynamically responded to the changes in HCV screening and treatment guidelines, continually increasing access to HCV care. The GLC serves as a model of primary care-based HCV care that aims to achieve HCV microelimination in a safety-net health system. Our findings support the notion that for the United States to achieve elimination of HCV by 2030, generalists can and should provide HCV care, particularly in medically underserved patient populations.

Characteristics and Outcomes of Black and White Patients Hospitalized With Nonalcoholic Steatohepatitis: A Nationwide Analysis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an increasingly common etiology for liver-related hospitalizations in the United States. The aim of this study was to examine the differences of disease characteristics and outcomes between hospitalized Black and White patients with NASH. MATERIALS AND METHODS: We used the National Inpatient Sample (NIS) to identify all adult hospitalizations with NASH (ICD-10 code: K75.81) from 2016 to 2018. We compared demographic and clinical characteristics between Black and White patients. Multivariable models were computed to compare all-cause mortality, length of stay (LOS), and total hospital costs between the groups. RESULTS: There were 43,409 hospitalizations with NASH (41,143 White, 2266 Black). Black patients were less likely to have cirrhosis (33.6%) compared with Whites (56.4%), P <0.0001. Black patients were less likely to have esophageal variceal bleeding (1.2% vs. 3.5%), ascites (17.1% vs. 28.8%), and acute liver failure (16.2% vs. 28.9%) compared with Whites (all P <0.0001). These findings were consistent among patients with cirrhosis. Mortality was higher among Blacks compared with Whites (3.9% vs. 3.7%, adjusted odds ratio=1.34; 95% confidence interval: 1.05-1.71, P =0.018). Compared with Whites, Blacks had a longer LOS (6.3 vs. 5.6, P <0.001), and higher hospital costs ($18,602 vs. $17,467; P =0.03). CONCLUSION: In this large population of inpatients with NASH, Black patients were less likely to have cirrhosis and liver disease-related complications, but had overall worse hospital mortality, longer LOS, and higher hospital costs. Further research is warranted to elaborate on factors that generate the health inequities in NASH outcomes between Black and White patients.

Safe co-administration of direct-acting antivirals and direct oral anticoagulants among patients with hepatitis C virus infection: An international multicenter retrospective cohort study.

Treatment for hepatitis C virus (HCV) with direct-acting antivirals (DAA) is advantageous over previous treatment options due to high efficacy, short treatment duration, and relatively few drug interactions. Similarly, direct oral anticoagulants (DOAC) are generally preferred over warfarin for the management of thrombosis and atrial fibrillation due to a favourable safety profile. Direct-acting antivirals inhibit DOAC transport through P-glycoprotein inhibition leading to a theoretical increase in bleeding risk. We evaluated the incidence of bleeding in patients who received concurrent DAA and DOAC therapy and stratified the analysis based on the patient's cirrhosis status. We conducted a multicenter, retrospective cohort study to evaluate bleeding in patients with HCV and cirrhosis compared to patients with HCV without cirrhosis. Patients receiving at least 1 month of overlapping DAA and DOAC therapy between May 2017 and August 2020 at 11 medical centers in the United Kingdom and three medical centers in the United States were included. Charts were manually reviewed to identify baseline characteristics as well as thromboembolic or bleeding events. Bleeding events were categorized as major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). Of 204 total patients, 36 patients (18%) had cirrhosis and 168 patients (82%) did not have cirrhosis. The majority of patients were male (79%) and Caucasian (75%). Sofosbuvir/velpatasvir (32%) and rivaroxaban (57%) were the most commonly prescribed DAA and DOAC, respectively. Leading indications for anticoagulation included thrombosis (75%) and atrial fibrillation (21%). There were three MB events (1.5%) all of which occurred in patients with additional risk factors (age over 65 and on antiplatelet therapy) and no CRNMB occurred while on DOAC and DAA therapy. Of the three MB, one occurred in a patient with cirrhosis and two in patients without cirrhosis, RR 1.23 (0.56-2.76). In conclusion, in this multicenter cohort study of concurrent DAA and DOAC use, MB was uncommon and there was no CRNMB. There was no significant difference in bleeding events among patients with cirrhosis compared to those without cirrhosis. These findings support the use of DAA among patients requiring DOAC.

Implementation of a Hepatocellular Carcinoma Screening Program for At-risk Patients Safety-Net Hospital: A Model for National Dissemination.

OBJECTIVE: This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population. BACKGROUND: Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients. METHODS: In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance. RESULTS: From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32-282). Median overall survival for treated patients was 32 months. CONCLUSIONS: Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program's success. Next steps include expanding the program to additional at-risk populations.

Using vibration controlled transient elastography and FIB-4 to assess liver cirrhosis in a hepatitis C virus infected population.

ABSTRACT: We assessed the performance characteristics of the Fibrosis-4 (FIB-4) score in a veteran population with chronic hepatitis C virus (HCV) infection and used vibration controlled transient elastography (VCTE) as the gold standard.All VCTE studies were performed by a single operator on United States veterans with HCV infection presenting for care at the Atlanta VA Medical Center (AVAMC) over a 2 year period. VCTE liver stiffness measurements (LSM) were categorized as cirrhotic if LSM was >12.5 kPa and non-cirrhotic if LSM was ≤12.5 kPa. FIB-4 scores ≤3.25 were considered non-cirrhotic and scores >3.25 were considered cirrhotic. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the FIB-4 score. A second analysis was done which identified and excluded indeterminate FIB-4 scores, defined as any value between 1.45 and 3.25.When FIB-4 was used to screen for liver cirrhosis using VCTE as the gold standard, sensitivity was 42%, specificity was 88%, PPV was 62%, and NPV was 76%. When indeterminate FIB-4 scores were excluded from the analysis, sensitivity was 95%, specificity was 61%, PPV was 62%, and NPV was 94.4%. In a veteran population with chronic HCV infection, we found the sensitivity of the FIB-4 score to be unacceptably low for ruling out liver cirrhosis when using a binary cutoff at 3.25. Using a second staging method like VCTE may be an effective way to screen for liver cirrhosis in persons with chronic HCV, especially when the FIB-4 score is in the indeterminate range.

Differences in inpatient and outpatient hepatitis C virus prevalence and linkage to care rates in a safety net hospital hepatitis C screening program.

BACKGROUND AND AIM: Routine screening for hepatitis C virus (HCV) infection is crucial in identifying the 50% of infected persons unaware of their infection. We added an inpatient screening initiative to our successful outpatient HCV screening program in an urban, safety-net hospital. METHODS: From March 2017 to December 2019, HCV screening was performed in inpatient and outpatient settings at Grady Health System. We compared care cascade outcomes, including anti-HCV testing, RNA testing, and linkage to care (LTC) between these settings. RESULTS: A total of 29 751 patients were tested for anti-HCV: 8883 inpatients and 20 868 outpatients. The anti-HCV population was predominantly Black (76.2%) and male (67.9%). The total anti-HCV prevalence was 8.9%, with 14% of inpatients and 6.7% of outpatients testing positive. RNA testing was performed on 86%. The prevalence of active HCV infection was 59.3% in those that were anti-HCV positive; inpatient prevalence was 66%, and outpatient was 53.8%. Of those with active infection, 67.5% were linked to care (57.3% of inpatients and 77.8% of outpatients). CONCLUSION: We found significant differences in prevalence of anti-HCV and LTC rates between inpatients and outpatients during an HCV screening program. Higher anti-HCV prevalence among inpatients may be due a higher prevalence of non-birth year HCV risk factors. LTC rates were lower in the inpatient setting despite a robust linkage strategy. The striking prevalence of HCV in both settings warrants continued screening, expansion to additional settings, and novel strategies to improve inpatient linkage rates, especially in the setting of new universal HCV screening guidelines.

Pretreatment Assessment of Psychosocial Readiness Is Not Associated with Improved Treatment Outcomes in a Safety-Net HCV Treatment Clinic.

OBJECTIVES: Hepatitis C virus (HCV) is highly curable with antiviral therapy, and traditionally, treatment adherence has been critical for treatment success. We sought to determine whether assessing HCV treatment readiness with a structured treatment readiness tool was associated with increased rates of adherence and cure among patients at a safety-net HCV clinic. METHODS: We administered the Psychosocial Readiness Evaluation and Preparation for HCV Treatment (PREP-C) tool to 50 patients and compared them with 50 patients who received the usual care. The outcome measures included achievement of treatment milestones (eg, adherence to treatment, clinic visit attendance) and sustained virologic response (cure). RESULTS: We found no association between receiving the PREP-C assessment and outcomes, including referral to or starting HCV treatment, adherence to treatment, and HCV cure. CONCLUSIONS: We found that receiving the PREP-C assessment did not improve treatment outcomes, suggesting that targeted pretreatment assessment is unnecessary even in a medically and psychosocially complex population.

Organic contaminant sorption parameters should only be compared across a consistent system of linear functions.

Modeling contaminant sorption data using a linear model is very common; however, the rationale for whether the y-intercept should be constrained or not remains a subject of debate. This article justifies constraining the y-intercept in the linear model to zero. By doing so, one imposes consistency on the system of linear equations, allowing for direct comparison of the sorption coefficients.

Defining the hepatitis C cure cascade in an Urban health system using the electronic health record.

Hepatitis C virus (HCV) infection is a public health threat. The electronic health record (EHR) can be used to monitor patients along the HCV cure cascade and highlight opportunities for interventions to improve cascade outcomes. We developed an HCV patient registry using data from Grady Health System's (GHS) EHR and performed a cross-sectional analysis of 72 745 GHS patients who received anti-HCV testing from 2004 to 2016. We created a testing cascade: (1) anti-HCV reactive, (2) HCV RNA tested and (3) HCV RNA detectable; and a cure cascade: (1) HCV RNA detectable, (2) engaged in care, (3) treatment prescribed, (4) sustained virologic response (SVR) tested and (5) SVR documented. A total of 9893 (14%) had reactive anti-HCV tests of 72 745 patients tested, 5109 (52%) of these had HCV RNA tested, and 4224 (43%) were HCV RNA detectable. A total of 2738 (65%) of 4224 with detectable RNA were engaged in care, 909 (22%) were prescribed antiviral therapy, and 354 (8%) achieved SVR. Factors associated with HCV treatment included cirrhosis, tobacco use, depression, diabetes, obesity, alcohol use, male gender, black race and Medicare insurance. Uninsured patients were significantly less likely to be prescribed HCV treatment. In conclusion, using EHR data, we identified high anti-HCV prevalence and noted gaps in HCV RNA testing, linkage to care and treatment. The EHR can be used to evaluate the effectiveness of targeted interventions to overcome these gaps.

Improved Hepatitis C Cure Cascade Outcomes Among Urban Baby Boomers in the Direct-Acting Antiviral Era.

OBJECTIVES: We compared outcomes of the hepatitis C virus (HCV) cure cascade (ie, the path a patient follows from diagnosis to cure), including antiviral treatment outcomes, from 2 HCV screening programs. Our objective was to assess whether treatment uptake and HCV cure rates improved in the cohort screened after the release of all-oral HCV direct-acting antiviral therapies. METHODS: We retrospectively compared outcomes of the HCV cure cascade from a cohort of newly diagnosed patients screened during 2012-2014 (period 1) with outcomes from a cohort of newly diagnosed patients screened during 2015-2016 (period 2) at Grady Health System in Atlanta, Georgia. Cure cascade outcomes included HCV antibody (anti-HCV) and RNA testing, linkage to care, antiviral treatment, and sustained virologic response. RESULTS: During period 1, 412 of 5274 (7.8%) persons screened were anti-HCV positive, and 264 (69.3%) of those tested were RNA positive. During period 2, 462 of 7137 (6.5%) persons screened were anti-HCV positive, and 240 (59.3%) of those tested were RNA positive (P = .003). The percentage of newly diagnosed patients who were treated during period 2 (64.0%) was 3 times that of newly diagnosed patients treated during period 1 (21.2%; P < .001). Both cohorts had similarly high levels of linkage to care (95.8% during period 1, 95.4% during period 2) and cure (92.6% during period 1, 95.5% during period 2). CONCLUSIONS: Over time, the prevalence of anti-HCV and HCV RNA positivity declined substantially, and linkage-to-care and cure rates remained high. Treatment uptake increased significantly after the introduction of all-oral direct-acting antiviral therapy. These findings suggest that combining large-scale screening initiatives with treatment programs can speed progress toward HCV elimination.

Optimizing cancer care for hepatocellular carcinoma at a safety-net hospital: The value of a multidisciplinary disease management team.

BACKGROUND: Hepatitis C (HCV) is the primary etiology of hepatocellular carcinoma (HCC) in the US multidisciplinary disease management teams (DMT) that optimize oncologic care. The impact of DMT for HCC in safety-net hospitals is unknown. METHODS: Patients diagnosed with HCC from 2009 to 2016 at Grady Memorial Hospital (GMH) were included. The primary aim was to evaluate referrals to care, receipt of therapy, and overall survival (OS) after DMT formation. Screening patterns of HCV patients for HCC were also examined. RESULTS: Of 204 HCC patients, median age was 58 years, with 81% male, 83% black. 46% presented with stage 4 disease, 53% had treatment with median OS 9.8 months. DMT formation was associated with increased referrals to surgery (49% vs 30%; P = .02), liver-directed therapy (58% vs 31%; P = .001), and radiation (13% vs 3%; P = .019). Patients were also more likely to get treatment (59% vs 41%; P = .026), with improved median OS (30.7 vs 4.9 months; P < .001). DMT did not alter HCV screening for HCC (23%). HCV patients screened for HCC had earlier stage disease (P = .001). CONCLUSION: Implementation of a DMT at GMH is associated with increased HCC patients referred for/receiving treatment, as well as improved survival. Few patients with HCV at risk for HCC are screened, despite DMT. Future efforts should aim to establish screening programs for HCV patients at risk for HCC.

Hepatitis B testing, care linkage, and vaccination coverage within a registry of hepatitis C infected patients.

BACKGROUND: Hepatitis B virus (HBV) infection testing among persons with hepatitis C virus (HCV) infection is necessary to appropriately care for these patients, yet uptake of HBV testing and vaccination in this population is suboptimal. METHODS: In a retrospective cohort analysis, we describe the prevalence of hepatitis B testing, linkage to hepatitis B care, and hepatitis B vaccination in patients with HCV infection within a large urban safety-net health system. Using a registry of HCV-infected patients with patient-level electronic health record data, that included demographic, clinical, and laboratory information from 2004 to 2016 from Grady Health System in Atlanta, GA, we describe (1) The prevalence of hepatitis B testing (hepatitis B surface antigen [HBsAg], core antibody [anti-HBc], surface antibody [anti-HBs]); (2) The proportion of HBsAg-positive persons receiving HBV DNA and e-antigen (HBeAg) as indicators for linkage to hepatitis B-directed care; and (3) The proportion of persons receiving hepatitis B vaccine. RESULTS: Of 4224 HCV-infected patients, 3629 (86%) had test results for HBsAg and 43 (1.2%) were HBsAg-positive. Of 2342 (55%) with test results for all three HBV serological markers, median age was 60 years, 67% were male, and 83% were African-American, 789 (34%) anti-HBc positive only, 678 (29%) anti-HBc/anti-HBs positive, 190 (8.1%) anti-HBs positive only, and 642 (27%) were HBV-susceptible. Of HBsAg-positive patients, 21% received HBV DNA and 40% HBeAg testing. The proportion of HBV-susceptible patients receiving at least 1 dose of hepatitis B vaccine was 322/642 (50%). CONCLUSIONS: In a large cohort of HCV-infected patients, we found a high prevalence of current or past HBV infection, but there were gaps in complete hepatitis B testing, hepatitis B-directed care, and hepatitis B vaccination. Strategies are needed to increase hepatitis B testing, linkage to care, and administration of the hepatitis B vaccine for HCV-infected persons in this healthcare system.

Evaluation of the Performance of Algorithms That Use Serial Hepatitis C RNA Tests to Predict Treatment Initiation and Sustained Virological Response Among Patients Infected With Hepatitis C Virus.

The structure of electronic medical record data prevents easy population-level monitoring of hepatitis C virus (HCV) treatment uptake and cure. Using an HCV registry from a public hospital system in Atlanta, Georgia, we developed multiple algorithms that use serial HCV RNA test results as proxy measures for initiation of direct-acting antiviral (DAA) treatment and sustained virological response (SVR). We calculated sensitivity and positive predictive values (PPVs) by comparing the algorithms with the DAA initiation and SVR results from the registry. From December 2013 to August 2016, 1,807 persons actively infected with HCV were identified in the registry. Of those, 698 initiated DAA treatment on the basis of medical record abstraction; of 442 patients with treatment start and/or end dates, 314 had documented SVR. Treatment algorithm 2 (a detectable HCV RNA result followed by 2 sequential HCV RNA test results) and treatment algorithm 5 (a detectable HCV RNA result followed by 2 sequential HCV RNA test results >6 weeks apart) had the highest sensitivity (87% and 85%, respectively) and PPV (80% and 82%, respectively) combinations. Four SVR algorithms relied on fulfilling treatment algorithm definitions and having an undetectable HCV RNA test result ≥12 weeks after the last HCV RNA result; sensitivity for all 4 algorithms was 79%, and PPV was 92%-93%. Algorithms using serial quantitative HCV RNA results can serve as proxy measures for evaluating population-level DAA treatment and SVR outcomes.

Incidence of Acute Kidney Injury in Patients Coinfected with HIV and Hepatitis C Virus Receiving Tenofovir Disoproxil Fumarate and Ledipasvir/Sofosbuvir in a Real-World, Urban, Ryan White Clinic.

Ledipasvir/sofosbuvir (LDV/SOF), an antiviral treatment for hepatitis C virus (HCV), and tenofovir disoproxil fumarate (TDF), an antiretroviral for treating human immunodeficiency virus (HIV), may be coadministered in patients coinfected with these viruses. A drug interaction between LDV and TDF could increase TDF-associated nephrotoxicity rates; however, there is minimal clinical evidence describing acute kidney injury (AKI) rates in this population. This study was conducted at a Ryan White-funded facility in Atlanta, Georgia, that cares for over 5,000 patients with AIDS. This retrospective cohort used chart review to assess occurrence of and risk factors for AKI in HIV/HCV-coinfected patients receiving LDV/SOF and antiretroviral therapy (ART). AKI rates were compared between TDF-containing and non-TDF-containing ART groups according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Additional evaluated risk factors for AKI included chronic kidney disease and use of boosted protease inhibitor-based ART. In the 117 included patients, the overall incidence of AKI was 27.3%. AKI occurred more frequently in the non-TDF group (13/86, 15.1% vs. 19/31, 61.3%, p < .001). All AKI was KDIGO stage 1. From multivariable logistic regression, the only independent predictor of AKI was treatment with non-TDF relative to TDF (adjusted odds ratio 6.51, 95% confidence interval 2.34-18.10, p < .001). In this real-world cohort of HIV/HCV-coinfected patients, KDIGO-defined AKI was common, but occurred less frequently in patients receiving TDF-based ART. Our study suggests that patients with normal baseline renal function can be safely treated with TDF and LDV/SOF without significant nephrotoxicity if renal function is closely monitored.

Multivariate soil fertility relationships for predicting the environmental persistence of 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitro-1,3,5-tricyclohexane (RDX) among taxonomically distinct soils.

After nearly a century of use in numerous munition platforms, TNT and RDX contamination has turned up largely in the environment due to ammunition manufacturing or as part of releases from low-order detonations during training activities. Although the basic knowledge governing the environmental fate of TNT and RDX are known, accurate predictions of TNT and RDX persistence in soil remain elusive, particularly given the universal heterogeneity of pedomorphic soil types. In this work, we proposed overcoming this problem by considering the environmental persistence of these munition constituents (MC) as multivariate mathematical functions over a variety of taxonomically distinct soil types, instead of a single constant or parameter of a specific absolute value. To test this idea, we conducted experiments where the disappearance kinetics of TNT and RDX were measured over a >300 h period in taxonomically distinct soils. Classical fertility-based soil measurements were log-transformed, statistically decomposed, and correlated to TNT and RDX disappearance rates (k-TNTand k-RDX) using multivariate dimension-reduction and correlation techniques. From these efforts, we generated multivariate linear functions for k parameters across different soil types based on a statistically reduced set of their chemical and physical properties: Calculations showed that the soil properties exhibited strong covariance, with a prominent latent structure emerging as the basis for relative comparisons of the samples in reduced space. Loadings describing TNT degradation were largely driven by properties associated with alkaline/calcareous soil characteristics, while the degradation of RDX was attributed to the soil organic matter content - reflective of an important soil fertility characteristic. In spite of the differing responses to the munitions, batch data suggested that the overall nutrient dynamics were consistent for each soil type, as well as readily distinguishable from the other soil types used in this study. Thus, we hypothesized that the latent structure arising from the strong covariance of full multivariate geochemical matrix describing taxonomically distinguished "soil types" may provide the means for potentially predicting complex phenomena in soils.

Highly Successful Hepatitis C Virus (HCV) Treatment Outcomes in Human Immunodeficiency Virus/HCV-Coinfected Patients at a Large, Urban, Ryan White Clinic.

BACKGROUND: The introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little "real-world" data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population. METHODS: This retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population. All HIV patients initiating HCV treatment from January 1, 2013 to November 30, 2015 were included in the analysis. The primary end point was sustained virologic response 12 weeks after the end of therapy (SVR12). RESULTS: A total of 172 patients initiated HCV treatment within the study period: 79% were male, 83% were black, 95% were HCV genotype 1, 79% were HCV treatment naive, and 16% had cirrhosis. At baseline, median CD4 was 494 cells/µL (interquartile range, 316-722) and 92% had HIV ribonucleic acid less than 40 copies/mL. The most common DAA initiated was ledipasvir/sofosbuvir (LDV/SOF) (85%), with 92% receiving 12 weeks of treatment. Overall, SVR12 was 93% by intention-to-treat analysis and 98% by per-protocol analysis. The majority of patients on LDV/SOF did not report any adverse effect. One patient in the ribavirin plus SOF group discontinued treatment due to adverse effect. CONCLUSIONS: In a cohort of mainly black, male, HIV/HCV-coinfected patients at a large, urban, Ryan White clinic, HCV treatment with DAAs resulted in high SVR12 rates and was well tolerated despite real-world challenges including medication access barriers and drug interaction concerns.