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Background & Aims Retreatment with glecaprevir/pibrentasvir (G/P) resulted in a rate of sustained virologic response 12 weeks after treatment completion (SVR12) of >90% in HCV genotype 1 (GT1) patients who previously failed a regimen of sofosbuvir plus an NS5A inhibitor (NS5Ai). This study investigated the prevalence and impact of baseline NS3 and NS5A resistance-associated substitutions (RASs) on the efficacy of G/P in prior GT1 sofosbuvir+NS5Ai failures and the persistence of treatment-emergent RASs. Methods Longitudinal samples from 177 patients enrolled in a phase IIIb, randomized pragmatic clinical trial were analyzed. Patients without cirrhosis were randomized to 12 or 16 weeks of G/P, and patients with compensated cirrhosis were randomized to G/P and ribavirin for 12 weeks or G/P for 16 weeks. Linkage of RAS was identified using Primer-ID next-generation sequencing at a 15% cut-off. Results Of 177 patients, 169 (95.5%) were PI-naive. All 33 GT1b-infected patients achieved SVR12. In GT1a-infected patients, baseline NS5A RASs were prevalent (74.5%, 105/141) but NS3 RASs were uncommon. Baseline NS3 RASs had no impact on G/P efficacy and patients with baseline NS5A RASs showed a numerically but not statistically significantly lower SVR12 rate compared to those without NS5A RASs (89% vs. 97%). SVR12 was achieved in 34 of 35 (97%) patients without NS5A baseline substitution, and 53 of 57 (93%), 35 of 40 (88%), 5 of 8 (63%) with single, double-linked, and triple-linked NS5A substitutions, respectively. Among 13 patients with virologic failure, 4 acquired treatment-emergent NS3 RASs and 10 acquired NS5A RASs. Conclusion Baseline NS5A RASs were highly prevalent. The presence of an increasing number of linked NS5A RASs in GT1a showed a trend in decreasing SVR12 rates, although no specific NS5A RASs or their linkage pattern were associated with lower SVR12 rates. Lay summary Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C infection, but treatment failure occurs in some patients. Retreatment of patients who previously failed a regimen consisting of sofosbuvir and an NS5A inhibitor with a regimen of glecaprevir and pibrentasvir (G/P) is >90% effective. Herein, we analyzed samples from these patients and showed that retreatment efficacy with G/P is lower in patients with double- or triple-linked NS5A resistance mutations than in patients with single or no NS5A resistance mutations. Clinical trial number NCT03092375 .

Hepatic encephalopathy (HE) is a complex and reversible neuropsychiatric syndrome that is associated with growing, substantial healthcare resource utilization. We aim to examine the predictors of 30-day readmission and hospitalization cost associated with HE. We conducted a cross-sectional study using the Nationwide Readmissions Database from 2010 to 2014. We assessed the readmission rates using multivariate logistic regression and established temporal trends of readmission rates and hospitalization cost. Weighted hierarchical logistic regression and generalized linear mixed models were used to identify predictors for nationally representative readmissions and hospitalization costs, respectively. The number of index hospitalizations with HE increased with a significant trend from 34,967 in 2010 to 44,791 in 2014. 16.8% of patients were readmitted within 30 days. Predictors increasing readmission risk included female sex, Elixhauser readmission score < 25, elective admission, patient’s state residential status, privately insured, number of diagnoses >13, and length of stay >4 days. Our results indicate there is a need to implement better management strategies to improve outcomes in patients hospitalized with HE to curb the increase in the economic burden associated with the disease.

BACKGROUND AND AIMS Our aim was to evaluate the impact of direct-acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD. APPROACH AND RESULTS This retrospective cohort study used the MarketScan database (2013-2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06-0.30) and non-SUD (aHR 0.11; 95% CI, 0.07-0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33-2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13-0.88) and non-SUD (aHR, 0.40; 95% CI, 0.25-0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37-1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03-2.24) and HCC (aHR, 1.69; 95% CI, 1.05-2.72) compared with non-SUD group. CONCLUSIONS Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.

INTRODUCTION: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS: Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1–6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS: Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0–4: 100%; weeks 5–8: 98.3%; and weeks 9–12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (

In the United States, Black people are disproportionately diagnosed with hepatitis C virus (HCV) compared with White people but are under-represented in HCV studies. In this US-based cross-sectional telephone survey study, we assessed willingness to participate (WTP) in health/medical research and attitudes and beliefs that may influence WTP among Black patients with HCV. Two hundred participants who had current or prior HCV diagnosis and self-identified as Black or African American were recruited from a national HCV cohort study and an outpatient hepatology clinic. WTP responses ranged from 1 (not at all willing) to 5 (very willing). Multivariable models were used to identify factors associated with the overall mean WTP score. In addition, an open-ended question solicited strategies to help increase research participation from the Black community. Overall, participants reported moderate WTP in research (Mean [95% Confidence Interval (CI)] = 3.78 [3.68, 3.88]). Of 13 types of research presented, participants reported lowest WTP for randomized controlled trials of medications (Mean [95% CI] = 2.31 [2.11, 2.50]). The initial multivariable model identified higher subjective knowledge of research as positively associated with WTP (Parameter estimate [95% CI] = 0.15 [0.02, 0.27]). Sensitivity analyses also identified higher perceived benefits of research as an additional factor associated with WTP. Qualitative findings indicate that greater community-based outreach efforts would increase accessibility of research opportunities. When given the opportunity to participate, Black participants with HCV reported moderate WTP in health/medical research. Research sponsors and investigators should employ community-based outreach to expand access and awareness of research opportunities.

Background and aims The long-term impact of hepatitis C virus (HCV) therapy with all-oral direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) has not been well-described. We characterized changes in PROs from pre-treatment to 12 months post-treatment in a real-world cohort. Methods PROP UP was a multi-center observational cohort study of 1,601 patients treated with DAAs at 11 U.S. gastroenterology/hepatology practices from 2015-2017. PROs were evaluated pre-treatment (T1) and 12 months post-treatment (T5). A minimally important change (MIC) threshold was prespecified as >5% change in PRO scores from T1 to T5. Multivariable analyses identified predictors of change. Results Three-quarters of patients were 55 or older; 45% were female, 60% were white, 33% were black, nearly half had cirrhosis. The most commonly-prescribed DAA regimens were sofosbuvir-based (83%) and grazoprevir/elbasvir (11%). Study retention was greater than 95%. On average, small improvements were observed at 3 months post-treatment in all PROs and sustained at 12 months post-treatment among patients with sustained virologic response (SVR). Clinically meaningful improvements were achieved in fatigue (mean change score: -3.7 [-4.2, -3.1]), sleep (mean change score: -3.1 [-3.7, -2.5]), abdominal pain (mean change score: -2.6 [-3.3, -1.9]) and functional well-being (mean change score: -7.0 [-6.0, -8.0]). Symptom improvements were generally not sustained with no SVR (n=52). Patients with cirrhosis and MELD ≥ 12 had the greatest improvements in functional well-being (-12.9 [-17.6, -8.1]). Conclusions The improvements in patient-reported outcomes reported by patients who achieved SVR following HCV DAA therapy were durable at 12 months post-treatment.

Medicaid prior authorization (PA) policies for treatment of hepatitis C virus (HCV) with direct‐acting antiviral (DAA) therapy are changing. We aimed to evaluate effects of changes in PA requirements on treatment uptake and to determine the factors associated with DAA treatment among Florida Medicaid beneficiaries with HCV. This is a retrospective cohort analysis of Florida’s Medicaid administrative claims and electronic medical records (2013‐2018). A total of 14,063 newly diagnosed patients with HCV were grouped based on human immunodeficiency virus (HIV) co‐infection and/or a substance use disorder (SUD) (7,735 HCV mono‐infected with a SUD, 5,180 HCV mono‐infected without a SUD, 564 HCV/HIV co‐infected with a SUD, and 584 HCV/HIV co‐infected without a SUD). Although the treatment rate increased three‐fold after June 1, 2016, when a fibrosis‐stage restriction was eliminated, only 8% received DAAs. Compared to HCV mono‐infected without a SUD, HCV mono‐infected with a SUD and HCV/HIV co‐infected with a SUD were 47% (adjusted hazard ratio, 0.53; 95% confidence interval, 0.47‐0.60) and 59% (adjusted hazard ratio, 0.41; 95% confidence interval, 0.28‐0.61) less likely to initiate DAAs. Those with HCV/HIV/SUD did not experience a DAA initiation increase after a fibrosis‐stage restriction was eliminated. Compared with Whites, Blacks were less likely to receive DAAs but were more likely to complete treatment. Use of medication‐assisted therapy was low, despite those on medication‐assisted therapy being 60% more likely to initiate DAA therapy and no more likely to discontinue therapy. Conclusion: Despite changes in Florida’s Medicaid PA requirements for DAA treatment, only 8% received treatment. Disparities in treatment access were found among patients with HIV and a SUD, and who were Black., In our retrospective cohort study analysis using Florida Medicaid claims data (2013‐2018), we examined the effects of prior authorization policy on access to direct‐acting antiviral (DAA) treatment and identified factors associated with disparities among Florida Medicaid patients with hepatitis C virus (HCV). Our work shows that the number of Florida Medicaid patients treated for HCV has increased, but treatment rates are still very low (8%); compared to HCV mono‐infected patients without substance use disorders (SUD), HCV mono‐infected patients with SUD and HCV/HIV patients co‐infected with SUD were 47% and 59% less likely to initiate DAAs, but no difference was observed in HCV/HIV patients co‐infected without SUD. Disparities in access to treatment continue among patients with SUD, blacks, and pregnant women among Medicaid patients with HCV.

We report the draft genome sequence for Pseudoalteromonas sp. strain JC3, an isolate obtained from an aquaculture facility for whiteleg shrimp ( Litopenaeus vannamei ). The JC3 genome suggests multiple mechanisms for microbial interactions, including a type VI secretion system and potential for antibiotic production.

Background: Breast cancer in the United States is diagnosed in over 90% of cases prior to evidence of distant metastasis (stages I–III) with approximately 70% of these cases classified as hormone receptor positive human epidermal growth factor receptor 2 negative (HR+HER2-).1 Despite primary surgery, radiation, and adjuvant endocrine/chemotherapy treatment options, approximately 20-30% of patients will experience relapse with distant metastases.2 Some clinical and pathological characteristics are known to be prognostic factors, but there are no standard definitions associated with level of risk. The objective of this study was to determine the extent of mortality associated with clinical and pathological characteristics of early breast cancer (EBC) using real-world data. Methods: Eligible patients from 2010–2016 Surveillance, Epidemiology, and End Results (SEER) data were aged ≥18 years and had a diagnosis of stage I, II, or III breast cancer with no distant metastases. Patients with HR-HER2- breast cancer were excluded. Mortality rates (95% confidence interval) by HER2 status and, for HR+HER2- tumors, by cancer stage, Bloom-Richardson (BR) grade, ipsilateral auxiliary lymph nodes status, and tumor size were estimated using Kaplan-Meier methods. Results: A total of 257,278 breast cancer patients were included: 214,578 HR+HER2-, 30,122 HR+HER2+, and 12,578 HR-HER2+. Mean age was 61.5 years, 99.1% were female, and 70.1% were white/non-Hispanic. The 5-year mortality rates were similar for HR+HER2- (12.3%) and HR+HER2+ (12.2%), whereas HR-HER2+ was numerically higher (16.8%). Within the HR+HER2- group, the 5-year mortality rates for subgroups are shown in Table 1. The highest mortality rate for both the node positive and micrometastases subgroups was approximately 30% for those who had 1–3 ipsilateral auxiliary lymph nodes, BR grade 3, and tumor size ≥5 cm. Conclusions: Patients with HR+HER2- EBC had similar mortality rates to patients with HR+HER2+ EBC. In patients with HR+HER2- EBC, higher mortality rates were numerically associated with ≥4 positive lymph nodes, BR grade 3, and greater tumor size. The effect on mortality was compounded with combinations of these histopathologic characteristics. References: 1. Howlander N, et al. J Natl Cancer Inst 2014;106:dju055; 2. Cardoso F, et al. Breast 2018;39:131-8. Table 1. Kaplan-Meier 5-year mortality estimates for patients with HR+HER2- early breast cancer by stage, grade, nodal status, and tumor size Node positiveN1mi: micrometastasesNode negativen=50,321n=10,096n=154,161 Mortality rate, % (95% CI)Mortality rate, % (95% CI)Mortality rate, % (95% CI)Overall18.15 (17.70–18.60)10.31 (9.51–11.11)10.54 (10.33–10.74)Stage INA7.29 (6.39–8.20)8.35 (8.13–8.56)Stage II12.56 (12.06–13.06)13.39 (11.91–14.87)16.69 (16.17–17.21)Stage III26.41 (25.61–27.22)19.10 (15.13–23.07)44.46 (40.69–48.23)1–3 Ips Ax nodes positive12.93 (12.43–13.43)9.96 (9.14–10.78)NA≥4 Ips Ax nodes positive24.75 (23.82–25.69)22.23 (15.64–28.82)NABR grade 325.62 (24.63–26.61)15.25 (13.09–17.41)14.24 (13.60–14.89)Tumor size Citation Format: Jacqueline Brown, Michael W Method, David R Nelson. Mortality rates associated with clinical and pathological characteristics of hormone receptor positive human epidermal growth factor receptor 2 negative early breast cancer: An analysis of the 2010-2016 surveillance, epidemiology, and end results data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-18.

BACKGROUND: The prevalence and risk factors for non-adherence to direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) in clinical practice settings are under-studied. OBJECTIVES: (1) To quantify DAA non-adherence in the total cohort and among subgroups with and without mental health conditions, alcohol use, and substance use, and (2) to investigate patient- and treatment-level risk factor non-adherence. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1562 patients receiving DAAs between January 2016 and October 2017 at 11 US medical centers including academic and community practices. MAIN MEASURES: Self-reported medication non-adherence, defined as any missed doses in the past 7 days, surveyed early (T2: at 4 ± 2 weeks) and late in treatment (T3: 2–3 weeks prior to end of treatment). Non-adherence to post-treatment follow-up visits was defined as absence of lab results after DAA therapy completion. KEY RESULTS: Of 1447 patients, 162 (11%) reported non-adherence at T2 or T3. Medical records indicated 262 (17%) of the 1562 participants had not returned for post-treatment visits. At baseline, 37% of patients reported mental health conditions, 15% reported alcohol use, and 23% reported using substances in the previous year. Baseline characteristics associated with DAA non-adherence included alcohol use (OR 1.96), younger age (< 35 years vs. > 55 years: OR 3.40), non-white race (OR > 2.26), and DAA treatment cohort, but not substance use or mental health condition. Non-adherence to follow-up exhibited association with younger age and a higher baseline overall symptom burden. Among 1287 patients with evaluable sustained virologic response (SVR) data, 53 patients (4%) did not achieve SVR. The bivariate correlation between adherence and SVR was negligible (r = 0.01). CONCLUSIONS: DAA non-adherence was low and SVR rates were high. Mental health conditions, substance use, and alcohol use should not disqualify patients from DAA therapy. Patients with alcohol use disorder before DAA therapy initiation may benefit from targeted on-treatment support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05394-9) contains supplementary material, which is available to authorized users.

Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT‐HCC) versus completely treated (CT‐HCC). HCC status was based on imaging 6 months before or 2 months after start of DAA therapy. Absence and presence of enhancing lesions after HCC treatment defined CT‐HCC and PT/UT‐HCC, respectively. Using minimally adjusted logistic regression, the association between the presence of HCC and SVR rates was estimated. Among the 1,457 patients with cirrhosis from HCV‐TARGET with complete virologic data (per‐protocol population) who did not undergo liver transplantation during treatment and followup, 1,300 were without HCC, 91 with CT‐HCC, and 66 with PT/UT‐HCC. Most patients were genotype 1 (81%) and treatment‐experienced (56%), 41% had history of prior decompensation, and the median pretreatment Model for End‐Stage Liver Disease was 9 (range 6‐39). The SVR rates were 91% for patients without HCC, 84% for CT‐HCC, and 80% for PT/UT‐HCC. The presence of HCC (versus not having HCC) was associated with significantly lower odds of achieving SVR (odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.33‐0.81; P = 0.003). However, among those with HCC, HCC treatment status (PT/UT‐HCC versus CT‐HCC) did not show association with SVR (OR = 0.79, 95% CI: 0.35‐1.79, P = 0.569). Conclusions: The presence of HCC reduces the likelihood of SVR by 50%, but with no evident difference in those with completely treated HCC versus partially treated/untreated HCC.

BACKGROUND: 50% of liver cancer is caused by hepatitis C virus (HCV). Baby boomers are at increased risk and are recommended for one-time HCV screening. However

Patients infected with hepatitis C virus (HCV) treated with interferon‐free direct‐acting antivirals may still require ribavirin. However, ribavirin is associated with adverse events that can limit its use. This open‐label, multicentre, Phase 3 study evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r + DSV) with low‐dose ribavirin for 12 weeks in genotype 1a‐infected patients without cirrhosis. The primary efficacy endpoint was sustained virologic response at post‐treatment Week 12 (SVR12). The primary safety endpoint was haemoglobin

Introduction and aim Direct-acting antiviral (DAA) agents are highly effective for treatment of chronic hepatitis C virus (HCV) yet access to treatment remains a serious challenge. The aim of this study was to identify barriers to treatment initiation with DAA-containing regimens in an urban clinic setting. Materials and methods A retrospective cohort of all chronic HCV patients seen in an urban academic practice in Jacksonville, FL, USA from 1/2014 to 1/2017 was analyzed. Baseline characteristics were recorded and a review of medical records was performed to identify barriers to treatment initiation and overall success rates. Results Two-hundred and forty patients with chronic HCV were analyzed. Fifty-six percent of patients were African-American and 63% were insured through Medicaid/county programs or uninsured. Sixty-nine percent had barriers to initiating antiviral therapy categorized as psychosocial (n = 112), provider (n = 26), medical (n = 20), and insurance-related factors (n = 7). The most commonly encountered psychosocial barriers included failure to keep appointments (79/240, 33%), active substance abuse (18/240, 8%), and failure to obtain laboratory testing (11/240, 5%). Overall, only 27% of patients evaluated were initiated on DAA-containing regimens with 18% reaching SVR12 within the 36-month study period. Conclusion In conclusion, only 27% of patients who presented to an urban academic practice with chronic HCV received DAA-containing regimens over a 36-month period. Psychosocial issues were the major barriers to antiviral therapy. These findings illustrate the need for an integrated approach that addresses psychosocial factors as well as comorbidities and adherence to care in order to increase rates of HCV treatment in at risk patients.

There are limiteddata on long-term changes in the gut microbiome after acute lymphoblastic leukemia (ALL) therapy. We compared the gut microbial composition in stool samples of nine survivors of childhood ALL with 10 healthy sibling controls using 16S rRNA gene sequencing. Analysis of beta diversity within family units demonstrated a significant difference in bacterial strains between patients and healthy siblings. A significant difference in alpha diversity between patients and their healthy siblings was noted using Pielou's evenness. The composition of the gut microbiome differs between pediatric ALL survivors and healthy sibling controls for years after completion of therapy.

Background and aims Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach and results We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. Conclusions This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

Introduction The objective of this study was to measure the influence of differences in out-of-pocket (OOP) costs for type 2 diabetes (T2D) medications on within-patient adherence behavior towards combination drug therapy regimens. Methods This was an observational, retrospective, paired sample study in patients with T2D using longitudinal pharmacy data from the 2009–2014 Medical Expenditure Panel Survey (MEPS) augmented with socio-demographic factors. We took a within-patient approach to minimize confounding effects by including patients who maintained the same number of diabetes drug classes over 2 years of MEPS. For each patient, we selected the most and least costly drug classes in the second year and examined their corresponding adherence behavior measured by medication possession ratio. The primary hypothesis tested the significance of the correlation between magnitude of the OOP cost difference and behavioral response in adherence. Results Analysis included 1189 patients representing over 4.2 million US residents with T2D. A significant negative correlation (p

Background The stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies. Results This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways. Conclusions The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (horn flies and Glossina) and non-blood-feeding flies (house flies, medflies, Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.

Approved treatment for hepatitis C virus (HCV) with all-oral direct-acting antivirals (DAA) therapy is now entering into its fourth year; however, little has been reported on the real-world clinical (decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]) and economic outcomes. A retrospective cohort analysis of the Truven Health MarketScan Database (2012-2016) was conducted. In a cohort of 26,105 patients with newly diagnosed HCV, 30% received all-oral DAA therapy (DAA group) and 70% were not treated (untreated group). Multivariate Cox proportional hazards models were used to compare the risk of developing HCC and DCC, stratified by cirrhosis status. Among patients with cirrhosis (n = 2157), DAA therapy was associated with a 72% and a 62% lower incidence of HCC (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.15-0.52) and DCC (HR, 0.38; 95% CI, 0.26-0.56). Similarly, DAA therapy was associated with a 57% and a 58% lower incidence of HCC (HR, 0.43; 95% CI, 0.26-0.71) and DCC (HR, 0.42; 95% CI, 0.30-0.58) in patients with noncirrhotic HCV (n = 23,948). A propensity score-matched cohort of 8064 HCV-infected patients who had at least a 12-month follow-up after HCV treatment was included for economic analysis. For patients with cirrhosis in the DAA group, the mean adjusted liver-related costs ($1749 vs. $4575; P < 0.001) and all-cause medical costs ($19,300 vs. $33,039; P < 0.001) were significantly lower compared with those in the untreated group. The mean adjusted costs were not statistically different between the two groups among patients without cirrhosis. Conclusion: In the short term, all-oral DAA treatment for HCV infection was associated with a decreased risk of developing HCC and DCC, resulting in decreased health care costs, especially in patients with cirrhosis. A longitudinal study is necessary to confirm our findings.

We characterized the prevalence of obesity among Florida children 2–19 years old using electronic health records (EHRs). The obesity prevalence for 331,641 children was 16.9%. Obesity prevalence at 6–11 years (19.5%) and 12–19 years (18.9%) were approximately double the prevalence of obesity among children 2–5 years (9.9%). The highest prevalence of severe obesity occurred in rural Florida (21.7%) and non-Hispanic children with multiple races had the highest obesity prevalence (21.1%) across all racial/ethnic groups. Our results highlight EHR as a low-cost alternative to estimate the prevalence of obesity and severe obesity in Florida children, both overall and within subpopulations.

Our aim was to develop and validate a practical US healthcare claims algorithm for identifying incident lung cancer that improves on positive predictive value (PPV) and sensitivity observed in past studies.Patients newly diagnosed with lung cancer in Surveillance, Epidemiology, and End Results (SEER) (gold standard) were linked with Medicare claims. A 5% Medicare "other cancer" sample and noncancer sample served as controls. A split-sample validation approach was used. Rules-based, regression, and machine learning models for developing algorithms were explored. Algorithms were developed in the model building subset. Rules-based algorithms and those with the highest F scores were evaluated in the validation subset. F scores were compared for 1000 bootstrap samples. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives.A practical single-score algorithm derived from a logistic regression model had sensitivity = 78.22% and PPV = 78.50% (F score: 78.36). The algorithm was most likely to misclassify older patients (ages ≥80 years) or with missing data in the SEER registry, shorter follow-up time in Medicare (3 months), insurance through Veterans Affairs,1 cancer in SEER, or certain Charlson comorbidities (dementia, chronic pulmonary disease, liver disease, or myocardial infarction).In this dataset, a practical point-based algorithm for identifying incident lung cancer demonstrated significant and substantial improvement (7.9% and 23.9% absolute improvement in sensitivity and PPV, respectively) compared with a current standard.

Introduction With obesity rates and obesity-related healthcare costs increasing, policy makers must understand the scope of obesity across populations. Objective This study sought to characterize adult obesity using electronic health records (EHRs) available from a statewide clinical data research network, the OneFlorida Clinical Research Consortium, which contains claims and EHR data from over 12 million patients in Florida. The primary aim was to compare EHR-based Florida obesity rates with those rates obtained from the Behavioural Risk Factor Surveillance System (BRFSS). Methods Body mass index from OneFlorida patient data (2012-2016) was used to characterize obesity among adults 20-79 years old. Obesity rates from both OneFlorida and BRFSS (2013) were reported by demographics and by county. Results Among the 1,344,015 adults in OneFlorida with EHR data and who met inclusion criteria, the obesity rate was 37.1%. Women had higher obesity rates compared with men. Obesity rates varied within racial/ethnic groups, with the highest rate among African-Americans (45.7%). Obesity rates from OneFlorida were consistently higher than those found in BRFSS (overall 27.8%). Conclusions Utilizing clinical big data available through hospital system and health partner collaborations provides an important view of the extent of obesity. Although these data are available only from healthcare users, they are large in scope, directly measured and are available sooner than commonly used national data sources.

While community stakeholder engagement is becoming increasingly common in health care, operationalized training materials to support this learner population (community members) are scarce. Instructional design principles were used to create an Open Educational Resource (OER) to support the involvement of community stakeholders in health care research at a university health science center. Prior to the development of this project, a formal group, whose members named themselves Citizen Scientists (CSs), already existed to offer lay perspective on clinical and translational research studies. These CSs are involved in a wide range of active committees within the university’s college of medicine. The challenge of this program, however, is that the CSs require training to engage in these activities (e.g., reviewing research proposals). This design and development research case outlines the instructional design processes, and formative evaluation methods and results of the creation of an OER. While the description of the instructional design processes can be useful for similar project implementations, information on methods and results from the formative evaluation add the following benefits: (a) help community stakeholders to analyze whether projects’ goals have been met, (b) present project aspects that could be improved, and (c) support other communities by creating a model for project evaluation based on similar contexts and with similar project goals.

Introduction: There is a consistent increase in prevalence of obese type 2 diabetes (T2D) patients, many of whom require insulin treatment. As endogenous insulin secretion dwindles and progressively increasing body weight worsens insulin resistance, exogenous insulin doses can be quite high. This presents unique disease management challenges to patients, treating physicians, and the health systems. These challenges could lead to therapeutic inertia and result in poor glycemic control (continuous increase or persistently high glycated hemoglobin [A1c]). Therefore, examining the A1c trajectory over a significant period could detect the existence and magnitude of therapeutic inertia. Further segmenting the patients based on their A1c trajectory over time would help formulate management strategies with tailored interventions to targeted patient segments with signs of therapeutic inertia. Objective: To segment obese patients with T2D on U-100 basal-bolus regimen based on A1c trajectory over a 3-year period. Methods: Adults with ≥2 T2D claims who were on U-100 basal-bolus regimen and with body mass index ≥30 kg/m2 or diagnosis codes for obesity during the identification period (APR2014-SEP2015) in the Veterans Health Administration database were included. The study period was OCT2013-SEP2018 and patients were required to have continuous enrollment for ≥6 months pre- and ≥3 years post-index periods. We captured the A1c pattern at 6-month intervals over a 3-year period. Only patients with A1c in at least 4 of the 6 time periods were included. A longitudinal unsupervised trajectory clustering method using the traj R package was implemented. Twenty-four features of A1c trajectory were examined followed by feature reduction using factor analysis. Based on the selected features, K-means clustering was used to identify patient segments based on the A1c trajectory. We extended the approach by repeating the same process as above among patient cluster with stable A1c trajectory to detect further A1c patterns. Results: A total of 45,520 patients were included. Four patient clusters were identified based on distinct patterns of A1c trajectory. The first cluster has descending A1c over time (N=8,325; 18.3%) while the second one has ascending A1c over time (N=8,123; 17.8%). Among patients with stable A1c trajectory, two more clusters were identified: stable high (N=10,654; 23.4%) with persistently high A1c around 9.0% and stable low (N=18,378; 40.4%) with persistently low A1c around 7.2%. Conclusions: By applying an unsupervised machine learning algorithm on A1c trajectory over time, this study identified over 40% of obese T2D patients on basal-bolus regimen belong to segments with poor A1c control during a three-year period, suggesting the significant existence of therapeutic inertia. Further research is planned to identify various forms of therapeutic inertia associated with these segments.

Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2–4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice.

Introduction Although registries can rapidly identify clinical study participants, it is unknown which follow up methods for recruiting are most effective. We examined the efficacy of three communication strategies for recruiting and enrolling patients who were identified via a contact registry (i.e., registry linked to a consent to re-contact program) into a clinical study. Methods Patients who met the study criteria were identified via the contact registry and targeted for recruitment. In condition 1, patients established in the university hepatology specialty clinics were contacted one time via phone call by the study coordinator and asked to participate (C1). In condition 2, non-established specialty clinic patients were mailed an IRB-approved letter with study information and instructions for calling the study coordinator to participate (C2). Condition 2A included patients who called within two weeks of receiving the letter (C2A); condition 2B included patients who did not call after receiving the letter but were subsequently contacted via phone call. Results A registry identified 1060 patients, of which 661 were eligible and targeted for recruiting. All 37 patients were reached in C1 and 17 (45.9%) were recruited. Nineteen of the 624 patients in C2A were reached and 10 were recruited whereas 120 of the 605 patients in C2B were reached and 53 (8.7%) were recruited. Seventy patients enrolled with C2B being the most effective (total, cost) recruitment strategy (n = 50) (p Conclusion The efficacy of enrolling patients identified via a contact registry into clinical trials varies based on the communication strategies used for recruiting.

We assessed the risk of chronic kidney disease (CKD) in chronic hepatitis C virus (HCV)-infected patients and the incidence reduction of CKD after receipt of HCV treatment. We also evaluated the risk of membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemia in chronic HCV patients. A retrospective cohort analysis of the Truven Health MarketScan Database (2008-2015) in the United States was conducted. In a cohort of 56,448 HCV-infected patients and 169,344 propensity score (1:3)-matched non-HCV patients, we examined the association of HCV infection with the incidence of CKD. Of 55,818 HCV patients, 6.6 % (n = 3666), 6.3% (n = 3534), and 8.3% (n = 4628) patients received either interferon-based dual, triple, or all-oral direct acting antiviral agent therapy, respectively, whereas 79% of patients did not receive any HCV treatment. Cox proportional hazards models were used to compare the risk of developing CKD in HCV patients compared with non-HCV patients and treated patients compared with untreated HCV patients. In a multivariate time-varying Cox regression model, HCV-infected patients had a 27% increased risk of CKD compared with non-HCV patients (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.18-1.37). Among HCV patients, individuals who received the minimally effective HCV treatment for dual, triple, or all-oral therapy had a 30% decreased risk of developing CKD (HR, 0.70; 95% CI, 0.55-0.88). In addition, HCV-infected patients experienced a twofold and a nearly 17-fold higher risk of MPGN (HR, 2.23; 95% CI, 1.84-2.71) and cryoglobulinemia (HR, 16.91; 95% CI, 12.00-23.81) respectively, compared with non-HCV patients. Conclusion: HCV-infected individuals in the United States are at greater risk of developing CKD, MPGN, and cryoglobulinemia. Minimally effective treatment of HCV infection can prevent the development of CKD, although the association was not significant for all-oral therapy. (Hepatology 2018;67:492-504).

The objective of this study was to identify factors associated with stroke, myocardial infarction (MI), all-cause mortality, or a diagnosis of ischemic heart disease (IHD) or unstable angina (UA), among patients newly-diagnosed with type 2 diabetes (T2DM) with no recent history of cardiovascular (CV) events who rapidly achieve and maintain HbAData were obtained from the Clinical Practice Research Datalink (CPRD) from January 1990 to December 2012. A nested case-control design was used with Cox proportional hazards analysis. Cases were identified by the first occurrence of stroke, MI, IHD, UA, or death within 5 years after HbAA total of 11,426 T2DM patients met the inclusion criteria for cases. Of these, 5,261 experienced a CV event. Stroke was the most frequent CV event (40%), followed by IHD (29%), MI (22%), and UA (9%). Mean HbA1c ≥7.0% over the length of exposure (vs 6.5 to7.0%) was associated with an increased risk of stroke, MI, and IHD. The use of anti-platelet medications at baseline was also associated with increased risk of stroke (HR = 1.82 [CI = 1.60-2.06]), MI (HR = 1.67 [CI = 1.38-2.03]), and IHD (HR = 1.85 [CI = 1.57-2.17]). Mean HbA1c 6.0% was associated with increased risk of stroke (HR = 1.29 [CI = 1.02-1.63]) and IHD (HR = 1.65 [CI = 1.25-2.19]). Use of nitrate medications at baseline was associated with increased risk of MI (HR = 2.83 [CI = 2.24-3.57]), IHD (HR = 4.32 [CI = 3.57-5.22]), and UA (HR = 10.38 [CI = 7.67-14.03]).Early and sustained HbA

Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

Background Although drug use is common in the population, drug users are sometimes excluded from research without justification. Two models of individualized study matching were compared for effectiveness in enrolling people who “endorsed current drug use” and those who “did not” into appropriate research. Methods Participants in the NIDA-funded Transformative Approach to Reduce Research Disparities Towards Drug Users study (Navigation Study) were recruited through a Clinical and Translational Science Award (CTSA) community engagement model. Of the 614 community-recruited adults, 326 endorsed current drug use (cases); 288 did not (controls). Participants were randomized to one of two intervention groups: Navigation as Usual (NAU) [individualized study matching through a Study Navigator] or Enhanced Navigation (N+) [individualized study matching plus transportation and other assistance through an Ambassador]. Rates of enrollment into research studies were compared. Results At 90 days, N+ vs. the NAU intervention was associated with higher enrollment among both drug users (36.0% N+ vs. 24.9% NAU) and non-drug users (45.5% N+ vs. 25.2% NAU). NAU attained the same rate of enrollment for users of drugs (24.9%) and non-users (25.2%); N+ had similar rates as well (36.0% drug users vs. 45.5% non-drug users). In addition, high rates of enrollment were achieved among all groups of participants, from 24.9% (drug users in NAU) to 45.5% (non-drug users in N+). Conclusions Both the NAU and N+ methods can reduce barriers and help users and non-users become part of the population that participates in research. Working with the local CTSA adds significant value to the research enterprise.

The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with CYP2C19 genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded CYP2C19 genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene–drug pairs: TPMT–thiopurines, IFNL3 (IL28B)–PEG IFN-α-based regimens, CYP2D6–opioids, CYP2D6/CYP2C19–antidepressants and CYP2C19–proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations. In addition, we have developed a broad array of educational programs for providers, trainees and students that incorporate personal genotype evaluation to enhance participant learning.

Many U.S. residents infected with hepatitis C virus (HCV) are baby boomers (born 1945-1965), who remain undiagnosed. Past CDC and USPSTF guidelines recommended one-time HCV testing for all baby boomers, with newer guidelines recommending universal screening for all adults. This retrospective cohort study examined electronic medical records for patient visits from 2015 to 2017 within the OneFlorida Data Trust and University of South Florida Health system. We assessed percentages of HCV tests ordered and completed across four age groups (those born before 1945, 1945-1965, 1966-1985, and after 1985). In 2019, we used logistic regression to examine factors associated with HCV test ordering and completion among baby boomers, including age, race, sex, number of primary care visits, HIV status, hepatitis diagnosis, and liver cancer history. All age groups had low rates of HCV test orders. 4.4% of baby boomers had a test ordered in 2015, and 6.7% in 2016. Of those, 94.5% and 89.7% completed testing, respectively. All other races/ethnicities had lower likelihood of testing completion than Whites (Blacks (aOR 0.82, 95%, CI 0.75-0.91); Asians (0.69, 0.52-0.92); Hispanics (0.29, 0.26-0.32)), although test orders were higher for Asians (1.48, 1.37-1.61) and Blacks (1.78, 1.73-1.82). Tests ordered (11.42, 10.94-11.92) and completed (2.25, 1.94-2.60) were more likely among those with hepatitis history. Test orders were more likely for HIV-positive patients (3.68, 3.45-3.93), but completion was less likely (0.67, 0.57-0.78). Interventions are needed to increase testing rates so that HCV infections are treated early, mitigating HCV-related morbidity and mortality, especially related to liver cancer.

Background & Aims Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. Methods Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. Results A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10–39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9–26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (−0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of Conclusion In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. ClinicalTrials.gov NCT01474811 . Lay summary Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.

Introduction: Health research registries have great potential to increase awareness of research opportunities among diverse patient populations and reduce disparities in clinical trial accrual. However, little research has focused on patients’ intentions to participate in clinical trials once they are enrolled in the registry and their intentions to remain in the registry over time. Methods: Patients (N = 312) enrolled in a university-based health research registry (i.e., Consent2Share) in the southeastern region of the US participated in an online survey. Results: Health research registry knowledge, perceived values, self-efficacy, trust, having chronic health concerns, and consent recall were positively correlated with intentions to remain enrolled in the research registry and participate in future clinical trials. Health research registry consent recall had significant positive associations with registry knowledge, perceived values, trust, registry retention, and participating in future trials. Conclusion: The process of consenting patients to the health research registry is important for recruitment, registry retention, and participation in future clinical trials. We identified key points of emphasis to expand participation in research registries as a strategy to increase clinical trial enrollment, such as deploying precision messages and tailored interventions. Keywords: Research registry, Clinical trials, Recruitment, Consent recall, Communication

Background & Aims A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs. Methods PROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment. Results Of 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21–53% of patients experienced >5% improved PROs while 23–36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35–55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements. Conclusions In real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities. Lay summary Patients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

BackgroundThe stable fly,Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the United States alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies.ResultsThis study examines stable fly biology by utilizing a combination of high-quality genome sequencing, microbiome analyses, and RNA-seq analyses targeting multiple developmental stages and tissues. In conjunction, manual curation of over 1600 genes was used to examine gene content related to stable fly reproduction, interactions with their host, host-microbe dynamics, and putative routes for control. Most notable was establishment of reproduction-associated genes and identification of expanded vision, chemosensation, immune repertoire, and metabolic detoxification pathway gene families.ConclusionsThe combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and knowledge will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship ofStomoxysto other blood-feeding (Glossina) and non-blood-feeding flies (medflies,Drosophila, house flies) will allow for understanding the evolution of blood feeding among Cyclorrhapha flies.

Aim: Within a treated migraine population, to evaluate if the sub-group meeting criteria for high disease-specific total costs is significantly different to the sub-group with medium and/or...

Background: Survivors of COVID-19 pneumonia often suffer from chronic critical illness (CCI) and require long-term hospitalization. Long-term acute care (LTAC) hospitals are vital in the care of CCI patients, but their role for patients post COVID-19 infection is not known. Barlow Respiratory Hospital (BRH) is a 105-bed, LTAC hospital network serving ventilator-dependent and medically-complex patients transferred from the ICUs of hospitals in southern California. We report patient characteristics of our first series of COVID-19 survivors admitted to the post-acute venue of an LTAC hospital. Methods: Single-center observational descriptive report of patients recovering from acute infectious complications of COVID-19 pneumonia requiring long-term respiratory support. Results: From 28 April to 7 September 2020, 41 patients were admitted to BRH for continued recovery from COVID-19 pneumonia. The length of stay at the transferring hospital was twice that of non-COVID patients admitted during the same time period. Median age: 68 [44-94] years, 61% male, 80.5% with tracheostomy, 51.2% on invasive mechanical ventilation, 22% receiving hemodialysis. All mechanical ventilation and hemodialysis interventions were initiated at the transferring hospital. Conclusions: To our knowledge, this is the first report to characterize CCI and medically complex COVID-19 patients transferred to the post-acute venue of an LTAC hospital. Patients on average spent over six weeks in the transferring hospital mostly in the ICU, are largely elderly, carry the known risk factors for COVID-19 infection, and experienced respiratory failure necessitating prolonged mechanical ventilation via tracheostomy. Our findings suggest that these patients will continue to require considerable medical interventions and treatments, including weaning from mechanical ventilation, owing to the numerous sequelae of the infection and the burden of acute-on-chronic diseases. As ICU survival rates improve, this research further emphasizes the important role of the LTAC hospital in responding to the COVID-19 crisis.

SummaryBackground Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. Aim To assess efficacy of all-oral HCV therapy in advanced liver disease. Methods Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. Results Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66–74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. Conclusions All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811

Background and Aim: Obtaining sufficient subjects into research studies is an ongoing barrier to conducting clinical research. Privacy rules add to the complexity of identifying qualified study subjects. The process described facilitates consent of patients coming to their clinically scheduled appointments who are asked to consent to having researchers review their electronic medical records (EHR), and if they meet study criteria for future research, being contacted by those researchers and asked if they wish to be involved in a research project. Methods: An interdisciplinary group representing the Institutional Review Board (IRB), Information Technology (IT), Hospital, University and Research developed an initial paper then electronic method to consent all patients attending a medical subspecialty clinic. All consent data are integrated to the EHR to facilitate linking to clinical information. Results: Although the paper consenting method resulted in over an 80% "yes" rate of consent, it was complicated by significant procedural challenges which prevented scalability. Revising the process has resulted in nearly 28,000 patients consenting in a 3 year period and in 20 IRB approved protocols using subjects who agreed to Consent2Share. Conclusions: A multi-disciplinary effort is essential to develop a successful electronic based, integrated process to assist investigators and patients to facilitate study subject accrual. Relevance for patients: Consent2Share more efficiently assists researchers in identifying and contacting potential study subjects that meet entrance criteria. The process provides a model to comply with the proposed Notice of Public Rule Making (NPRM) where institutions will be strongly encouraged to develop broad research consent procedures.

Hatcheries providing seed for bivalve mollusc aquaculture can suffer from disease outbreaks resulting in high losses of larvae. Previous research demonstrated the effectiveness of candidate probiotics Phaeobacter inhibens S4 (S4) and Bacillus pumilus RI06-95 (RI) in protecting the larvae of eastern oysters Crassostrea virginica, against bacterial challenge. In this study, the ability of this probionts in protecting larvae of other bivalve species, including northern quahog Mercenaria mercenaria, bay scallops Argopecten irradians, blue mussels Mytilus edulis, and razor clams Ensis directus, was investigated. Pretreatment of larvae with 106 colony forming units /ml probiotic S4 and a mixture of S4 and RI protected bay scallop larvae [relative percent survival (RPS): 69% ± 4%]. In pilot-scale hatchery trials, daily additions of candidate probiotics to the water of static tanks containing northern quahog or bay scallop larvae had no significant impact on larval growth and survival. Daily treatment of...

Objective Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants. Design HCV-TARGET, an international, prospective observational study evaluates clinical practice data on novel antiviral therapies at 44 academic and 17 community medical centres in North America and Europe. Clinical data were centrally abstracted from medical records. Selection of treatment regimen and duration was the investigator9s choice. The primary efficacy outcome was sustained virological response 12 weeks after therapy (SVR12). Results Between December 2013 and April 2015, 321 patients completed 12 weeks (n=283) or 16 weeks (n=38) of treatment with SOF and RBV. Prior treatment experience and cirrhosis was more frequent among patients in the 16-week regimen compared with 12 weeks (52.6% vs 27.6% and 63.2% vs 21.9%, respectively). Overall, SVR12 was 88.2%. The SVR12 in patients without cirrhosis was 91.0% and 92.9% for 12 or 16 weeks of therapy, respectively. In patients with cirrhosis treated for 12 or 16 weeks, SVR12 was 79.0% and 83%. In the multivariate analysis, liver cirrhosis, lower serum albumin and RBV dose at baseline were significantly associated with SVR12. Common adverse events (AEs) included fatigue, anaemia, nausea, headache, insomnia, rash and flu-like symptoms. Discontinuation due to AEs occurred in 2.8%. Conclusions In this clinical practice setting, SOF and RBV was safe and effective for treatment of patients with HCV GT2 infection. Trial registration number NCT01474811.

Background and aims Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. Methods In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. Results Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. Conclusions On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen.

Background & aimsRenal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).MethodsHCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort.ResultsA total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes.ConclusionsSustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Background & Aims: There are currently no validated claims-based indicators for identifying a worsening of disease in patients with inflammatory bowel disease (IBD). Therefore, we aimed to develop and validate indicators that identify flare-ups of IBD using data from Danish nationwide registries. Methods: Using Danish nationwide administrative data, we identified all patients with Crohn’s disease (CD) or ulcerative colitis (UC) who had at least one measurement of faecal calprotectin between 1 January 2015 and 31 June 2017. We tested several different claims-based indicators of disease flare-ups against levels of faecal (F-)calprotectin (no flare-up: Results: A total of 890 children and 4719 adults with CD, and 592 children and 5467 adults with UC were included in the study. During the observation period, 48–61% and 48–55% of the CD and UC patients, respectively, had no flare-up, 26–29% (CD) and 24–26% (UC) experienced a mild flare-up, and 12–23% (CD) and 21–27% (UC) experienced a severe flare-up. Combinations of indicators that could predict a flare-up in CD and UC adults included hospitalisation, surgery, initiation or switch of biological therapy, treatment with systemic steroids, locally acting steroids or topical 5-aminosalicylates, colonoscopy/sigmoidoscopy, and magnetic resonance imaging/computed tomography. In children, only the number of gastroenterology visits was significant as an indicator among UC patients, and none were seen in children with CD. Overall, the indicator combinations resulted in a predictive ability of 0.62–0.67. Conclusion: Administrative claims data can be useful for identifying patients exhibiting (F-calprotectin defined) flare-ups of their IBD. Clinically relevant events captured in the Danish national patient registry are associated with increased levels of calprotectin and hence increased disease activity, and can be used as valid outcomes in future studies.