Characteristics associated with time-to-treatment initiation for chronic Hepatitis C with new direct acting antivirals.

BACKGROUND: Interferon-free direct-acting antivirals (DAAs) were introduced in 2013 and have transformed the therapeutic landscape for chronic Hepatitis C (HCV). Although treatment is recommended for almost all persons infected with HCV, clinical and psychosocial factors may affect treatment initiation. METHODS: We conducted an observational cohort study of Kaiser Permanente Mid-Atlantic States members with prevalent or incident HCV infection identified from November 2013 through May 2016 to identify predictors of DAA initiation. We used Cox regression with time-dependent covariates to compare time to treatment by clinical, demographic and societal factors. RESULTS: Of 2962 patients eligible for DAA therapy, 33% (n = 980) initiated treatment over the study period. The majority of patients (97%) were persistent with therapy and most (95%) tested for sustained virologic response (SVR) achieved cure. We found no effect of race, insurance type or fibrosis stage on treatment initiation. We observed that patients aged 41-60 years (aHR: 2.014, 95% CI: 1.12, 3.60) and 61-80 years (aHR: 2.08, 95% CI: 1.15-3.75) had higher treatment rates compared to younger patients. Incident cases were more likely to be treated than prevalent cases (aHR: 3.05, 95% CI: 2.40-3.89). Patients with a history of substance use disorder (SUD) were less likely (aHR: 0.805, 95% CI: 0.680, 0.953) to be treated. CONCLUSIONS: In the first 3 years of DAA availability, one-third of patients with HCV initiated therapy, and almost all were persistent and achieved cure. While curative, DAAs remain highly priced. Triaging for non-clinical reasons or perceptions about patients will stall our ability to eradicate HCV.

Ursodeoxycholic Acid Treatment Preferentially Improves Overall Survival Among African Americans With Primary Biliary Cholangitis.

BACKGROUND: We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. METHODS: Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. RESULTS: Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. DISCUSSION: African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.

Accuracy of electronic health record data for the diagnosis of chronic obstructive pulmonary disease in persons living with HIV and uninfected persons.

PURPOSE: No prior studies have addressed the performance of electronic health record (EHR) data to diagnose chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH), in whom COPD could be more likely to be underdiagnosed or misdiagnosed, given the higher frequency of respiratory symptoms and smoking compared with HIV-uninfected (uninfected) persons. METHODS: We determined whether EHR data could improve accuracy of ICD-9 codes to define COPD when compared with spirometry in PLWH vs uninfected, and quantified level of discrimination using the area under the receiver-operating curve (AUC). The development cohort consisted of 350 participants who completed research spirometry in the Examinations of HIV Associated Lung Emphysema (EXHALE) study, a pulmonary substudy of the Veterans Aging Cohort Study. Results were externally validated in 294 PLWH who performed spirometry for clinical indications from the University of Washington (UW) site of the Centers for AIDS Research Network of Integrated Clinical Systems cohort. RESULTS: ICD-9 codes performed similarly by HIV status, but alone were poor at discriminating cases from non-cases of COPD when compared with spirometry (AUC 0.633 in EXHALE; 0.651 in the UW cohort). However, algorithms that combined ICD-9 codes with other clinical variables available in the EHR-age, smoking, and COPD inhalers-improved discrimination and performed similarly in EXHALE (AUC 0.771) and UW (AUC 0.734). CONCLUSIONS: These data support that EHR data in combination with ICD-9 codes have moderately good accuracy to identify COPD when spirometry data are not available, and perform similarly in PLWH and uninfected individuals.

Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection.

BACKGROUND AND OBJECTIVES: Studies evaluating the role of hepatitis C viral (HCV) infection on the progression of CKD are few and conflicting. Therefore, we evaluated the association of untreated HCV on kidney function decline in patients with stage 3-5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included members of Kaiser Permanente Southern California and Kaiser Permanente Mid-Atlantic States aged ≥18 years, with incident HCV and CKD diagnoses from January 1, 2004 to December 31, 2014. We used generalized estimating equations to compare the rate of change in eGFR between those with HCV and CKD versus CKD alone, adjusting for covariates. Cox proportional hazards models compared the risk of 25% decrease in eGFR and ESKD (defined as progression to eGFR<15 ml/min per 1.73 m2 on two or more occasions, at least 90 days apart) in those with HCV and CKD versus CKD alone, adjusting for covariates. RESULTS: We identified 151,974 patients with CKD only and 1603 patients with HCV and CKD who met the study criteria. The adjusted annual decline of eGFR among patients with HCV and CKD was greater by 0.58 (95% confidence interval [95% CI], 0.31 to 0.84) ml/min per 1.73 m2, compared with that in the CKD-only population (HCV and CKD, -1.61; 95% CI, -1.87 to -1.35 ml/min; CKD only, -1.04; 95% CI, -1.06 to -1.01 ml/min). Adjusted for covariates, the hazard for a 25% decline in eGFR and for ESKD were 1.87 (95% CI, 1.75 to 2.00) and 1.93 (95% CI, 1.64 to 2.27) times higher among those with HCV and CKD, respectively, compared with those with CKD only. CONCLUSIONS: Untreated HCV infection was associated with greater kidney function decline in patients with stage 3-5 CKD.

Increasing hepatitis C screening in a large integrated health system: science and policy in concert.

OBJECTIVES: To evaluate whether the updated 2013 US Preventive Services Task Force (USPSTF) hepatitis C virus (HCV) screening recommendations, related Affordable Care Act provisions, and the impending availability of efficacious therapies were associated with increased screening in an integrated health system. STUDY DESIGN: We analyzed 665,339 records of adult patients visiting Kaiser Permanente Mid-Atlantic States clinics from 2003 to 2014. METHODS: We used Cox proportional hazards to estimate time to HCV screening and confirmation after June 1, 2013, compared with prior. RESULTS: HCV screening steadily increased over time, but it jumped 29% (P <.01) from 2013 to 2014 versus 4% (P <.01) from 2012 to 2013. The adjusted hazard ratio for HCV screening since June 2013 was 2.40 (95% CI, 2.34-2.47) times higher than it was pre-intervention among the birth cohort (those born 1945-1965) and 2.00 (95% CI, 1.96-2.04) times higher in those born in other years, representing a 1.20-fold (95% CI, 1.17-1.24) greater increase in the screening rate among the birth cohort. We also identified variability in those thought to be at higher risk of HCV infection. CONCLUSIONS: HCV screening has been increasing in our healthcare system, more so since June 2013 and among the birth cohort. The availability of efficacious therapies and coverage policies coincident with the USPSTF recommendations may have facilitated access to screening and treatment in ways that were absent at the time of the 2012 CDC recommendations. Health systems must also be poised to make resources available to clinicians and patients in order to incentivize screening. Future research should inform a better understanding of incentives and barriers to screening and linkage to care from all stakeholder perspectives.

Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems.

BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD database from 2003 through 2014. We used multivariable modeling to assess the effects of factors associated with PBC prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS: We identified 4241 PBC cases among over 14.5 million patients in FOLD health systems; median follow-up was 5 years. Accuracy of the classification model was excellent, with an area under the receiver operating characteristic curve value of 93%, 94% sensitivity, and 87% specificity. The average patient age at diagnosis was 60 years; 21% were Hispanic, 8% were African American, and 7% were Asian American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted prevalence values were highest among women (42.8 per 100,000), White patients (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence was significantly lower among men and African Americans (10.7 and 19.7 per 100,000, respectively) than women and whites; men and African Americans were also less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P < .05). CONCLUSIONS: In an analysis of a large cohort of patients with PBC receiving routine clinical care, we observed significant differences in PBC prevalence and treatment by gender, race, and age.

Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment.

BACKGROUND & AIMS: There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States. We collected data from the Fibrotic Liver Disease consortium to investigate changes in the incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality. METHODS: We collected demographic and clinical data for the general patient population as well as PBC patients receiving care from 11 health systems in different regions of the United States (Northeast, Midwest, Northwest, and South) from January 1, 2003, through December 31, 2014. Annual percentage changes in PBC prevalence and incidence were estimated using join-point Poisson regression. Differences based on race, age, and gender were calculated with rate ratios. All-cause mortality was estimated using Cox regression with adjustment for patient characteristics and treatment with ursodeoxycholic acid (UDCA). Propensity scores were used to adjust for treatment selection bias. Analyses were adjusted by geographic regions. RESULTS: In our racially diverse cohort of 3488 patients with PBC (21% Hispanic, 8% African American, 7% Asian American), 70% had ever received UDCA. From 2006 through 2014, the prevalence of PBC increased from 21.7 to 39.2 per 100,000 persons. Adjusted annual percentage changes in prevalence differed among age groups (≤40 y, 41-50 y, 51-60 y, 61-70 y, and >70 y), ranging from 3.0% to 7.5% (P < .05). Incidence did not change significantly during the study period (4.2 vs 4.3 per 100,000 person-years in 2006 and 2014, respectively; P = .98). Ratios of prevalence for women vs men (3.9:1) and incidence for women vs men (3.2:1) were consistent over the study period. Among African Americans, the prevalence of PBC increased from 16.9 to 30.8 per 100,000 during the study period, and annual incidence ranged from 2.6 to 6.6 per 100,000 person-years. In adjusted analyses, an increased level of alkaline phosphatase at baseline was associated with significantly higher mortality (adjusted hazard ratios [aHR], 1.24; 95% CI, 1.04-1.48 for patients with levels 1-2 times the upper limit of normal and aHR, 2.27; 95% CI, 1.88-2.73 for patients with levels more than 3 times the upper limit of normal). UDCA treatment was associated with significantly reduced mortality (aHR, 0.57; 95% CI, 0.52-0.64). CONCLUSIONS: In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.

HIV Provider Documentation and Actions Following Patient Reports of At-risk Behaviors and Conditions When Identified by a Web-Based Point-of-Care Assessment.

We compared same-day provider medical record documentation and interventions addressing depression and risk behaviors before and after delivering point-of-care patient-reported outcomes (PROs) feedback for patients who self-reported clinically relevant levels of depression or risk behaviors. During the study period (1 January 2006-15 October 2010), 2289 PRO assessments were completed by HIV-infected patients. Comparing the 8 months before versus after feedback implementation, providers were more likely to document depression (74% before vs. 87% after feedback, p = 0.02) in patients with moderate-to-severe depression (n = 317 assessments), at-risk alcohol use (41 vs. 64%, p = 0.04, n = 155) and substance use (60 vs. 80%, p = 0.004, n = 212). Providers were less likely to incorrectly document good adherence among patients with inadequate adherence after feedback (42 vs. 24%, p = 0.02, n = 205). While PRO feedback of depression and adherence were followed by increased provider intervention, other domains were not. Further investigation of factors associated with the gap between awareness and intervention are needed in order to bridge this divide.

The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals.

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 <200 cells/mm3 (aOR 5.4, 95% CI 4.2-6.9) and HIV RNA >500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Streamlining Screening to Treatment: The Hepatitis C Cascade of Care at Kaiser Permanente Mid-Atlantic States.

Hepatitis C virus (HCV) screening is recommended for patients at risk and/or born during 1945-1965, but screening gaps persist. This new program screens target populations and enhances care linkage for chronically HCV-infected patients. Kaiser Permanente Mid-Atlantic States created a comprehensive HCV screening pathway, supported by a HCV care coordinator. The testing pathway includes HCV antibody (Ab), automatic HCV RNA for Ab-positive patients, coinfection and liver health tests, vibration-controlled transient elastography (VCTE), and a physician referral. A total of 11 200 patients were screened; 3.25% were HCV Ab positive, and 100% of Ab-positive patients received HCV RNA testing. Of HCV Ab-positive patients, 75.9% had chronic HCV, of which 80.8% underwent VCTE. HCV diagnosis was communicated to 94% of patients, and 70.9% had HCV documented in the electronic health record. The pathway shows promise in closing gaps, including improving HCV RNA testing, communicating diagnoses, and assessing liver fibrosis. Improved testing and linkage could increase curative treatment access.

HIV testing, staging, and evaluation.

HIV testing and incidence are stable, but trends for certain populations are concerning. Primary prevention must be reinvigorated and target vulnerable populations. Science and policy have progressed to improve the accuracy, speed, privacy, and affordability of HIV testing. More potent and much better tolerated HIV treatments and a multidisciplinary approach to care have increased adherence and viral suppression. Changes to health care law in the United States seek to expand the affordability and access of improved HIV diagnostics and treatment. Continued challenges include improving long-term outcomes in people on lifetime regimens, reducing comorbidities associated with those regimens, and preventing further transmission.

Factors associated with delayed hepatitis B viral suppression on tenofovir among patients coinfected with HBV-HIV in the CNICS cohort.

BACKGROUND: Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small cohorts of coinfected patients with HBV-HIV. We examined the effect of prior lamivudine (3TC) treatment and other factors on HBV DNA suppression with TDF in a multisite clinical cohort of coinfected patients. METHODS: We studied all patients enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort from 1996 to 2011 who had chronic HBV and HIV infection, initiated a TDF-based regimen continued for ≥ 3 months and had on-treatment HBV DNA measurements. We used Kaplan-Meier curves and Cox-proportional hazards to estimate time to suppression (HBV DNA level <200 IU/mL or <1000 copies/mL) by selected covariates. RESULTS: Among 397 coinfected patients on TDF, 91% were also on emtricitabine or 3TC concurrently, 92% of those tested were hepatitis B e antigen positive, 196 (49%) had prior 3TC exposure; 192 (48%) achieved HBV DNA suppression over a median of 28 months (interquartile range: 13-71). Median time to HBV DNA suppression was 17 months for those who were 3TC-naive and 50 months for those who were 3TC exposed. After controlling for other factors, prior 3TC exposure, baseline HBV DNA level >10,000 IU/mL, and lower nadir CD4 count were independently associated with decreased likelihood of HBV DNA suppression on TDF. CONCLUSIONS: These results emphasize the role of prior 3TC exposure and immune response on delayed HBV suppression on TDF.

An automated system for public health surveillance of school absenteeism.

Public Health-Seattle & King County established an automated system for monitoring school absenteeism data from 18 of 19 public school districts in King County, Washington. The system receives a daily aggregate count of the number of students enrolled and absent, stratified by school district, school name, and grade. A name and unique identifier are provided for each school and district, as well as the level (eg, elementary, middle, high, alternative, other) and zip code of each school. Files are transmitted to the health department daily and include data from the previous school day. Public Health-Seattle & King County developed a series of visualizations that summarize the data by day, week, and month for each level of stratification. The automated system for collecting and monitoring school absenteeism data was more acceptable, simple, timely, complete, and useful relative to traditional manual data collection methods.

Association between school closure and subsequent absenteeism during a seasonal influenza epidemic.

BACKGROUND: Mathematical models suggest that social distancing measures, such as school closures, may mitigate community transmission during an influenza pandemic. Because closures are disruptive to schools and families, they are rarely employed during seasonal influenza outbreaks. A rare circumstance enabled us to examine the association between school closure and absenteeism during a seasonal influenza outbreak when half of King County, Washington public schools closed for a winter recess 19-23 February 2007, while half remained open for all or part of the week. METHODS: Using absenteeism as a proxy for influenza activity, we tested the hypothesis that schools on break would experience lower rates of post-break absenteeism than schools remaining open. We conducted daily retrospective and prospective surveillance from 5 February-9 March 2007 in schools on break (n = 256) and in session (n = 205). We use generalized estimating equations with Poisson distribution to evaluate whether mean absenteeism after the break differed between schools on break and those in session, adjusting for baseline absenteeism and repeated measurements by schools over time. RESULTS: Results indicate no difference in post-break absenteeism in schools on break compared with schools that remained in session (relative risk = 1.07 [95% confidence interval = 0.96-1.20]). This result held in elementary schools (1.00 [0.91-1.10]), where absenteeism patterns are thought to be most representative of community influenza activity. CONCLUSION: We did not find that school closure during a seasonal influenza outbreak reduced subsequent absenteeism. However, limitations in this "natural experiment" hampered our ability to detect a benefit if one truly was present.

Diarrheal illness detected through syndromic surveillance after a massive power outage: New York City, August 2003.

OBJECTIVES: We investigated increases in diarrheal illness detected through syndromic surveillance after a power outage in New York City on August 14, 2003. METHODS: The New York City Department of Health and Mental Hygiene uses emergency department, pharmacy, and absentee data to conduct syndromic surveillance for diarrhea. We conducted a case-control investigation among patients presenting during August 16 to 18, 2003, to emergency departments that participated in syndromic surveillance. We compared risk factors for diarrheal illness ascertained through structured telephone interviews for case patients presenting with diarrheal symptoms and control patients selected from a stratified random sample of nondiarrheal patients. RESULTS: Increases in diarrhea were detected in all data streams. Of 758 patients selected for the investigation, 301 (40%) received the full interview. Among patients 13 years and older, consumption of meat (odds ratio [OR]=2.7, 95% confidence interval [CI]=1.2, 6.1) and seafood (OR=4.8; 95% CI=1.6, 14) between the power outage and symptom onset was associated with diarrheal illness. CONCLUSIONS: Diarrhea may have resulted from consumption of meat or seafood that spoiled after the power outage. Syndromic surveillance enabled prompt detection and systematic investigation of citywide illness that would otherwise have gone undetected.