Gonorrhea and Chlamydia Testing and Case Rates Among Women Veterans in the Veterans Health Administration.

BACKGROUND: United States (US) rates of sexually transmitted infection (STI) in women, especially gonorrhea and chlamydia, have increased over the past decade. Women Veterans may be at increased risk for STIs due to high rates of sexual trauma. Despite the availability of effective diagnostic tests and evidence-based guidelines for annual screening among sexually active women under age 25, screening rates for gonorrhea and chlamydia remain low in the US and among Veterans. OBJECTIVE: To examine patient characteristics and health system factors associated with gonorrhea and chlamydia testing and case rates among women Veterans in the Veterans Health Administration (VHA) in 2019. DESIGN: We performed a retrospective cohort study of all women Veterans in VHA care between January 1, 2018, and December 31, 2019. PARTICIPANTS: Women Veteran patients were identified as receiving VHA care if they had at least one inpatient admission or outpatient visit in 2019 or the preceding calendar year. KEY RESULTS: Among women under age 25, 21.3% were tested for gonorrhea or chlamydia in 2019. After adjusting for demographic and other health factors, correlates of testing in women under age 25 included Black race (aOR: 2.11, CI: 1.89, 2.36), rural residence (aOR: 0.84, CI: 0.74, 0.95), and cervical cancer screening (aOR: 5.05, CI: 4.59, 5.56). Women under age 25 had the highest infection rates, with an incidence of chlamydia and gonorrhea of 1,950 and 267 cases/100,000, respectively. Incidence of gonorrhea and chlamydia was higher for women with a history of military sexual trauma (MST) (chlamydia case rate: 265, gonorrhea case rate: 97/100,000) and those with mental health diagnoses (chlamydia case rate: 263, gonorrhea case rate: 72/100,000.) CONCLUSIONS: Gonorrhea and chlamydia testing remains underutilized among women in VHA care, and infection rates are high among younger women. Patient-centered, system-level interventions are urgently needed to address low testing rates.

Hepatitis B Virus-related Care Quality in Patients With Hepatitis B/Human Immunodeficiency Virus Coinfection Versus Hepatitis B Monoinfection: A National Cohort Study.

BACKGROUND: Guideline-adherent hepatitis B virus (HBV) care is critical for patients with HBV, particularly patients with HBV-human immunodeficiency virus (HIV) given increased risks of liver-related complications. However, a comprehensive assessment of HBV-related care in patients with HBV-HIV is lacking. METHODS: We retrospectively assessed adherence to HBV-related care guidelines in all patients with HBV-HIV and HBV monoinfection (HBV-M) in the national Veterans Health Administration healthcare system in 2019. RESULTS: We identified 1021 patients with HBV-HIV among 8323 veterans with chronic HBV. Adherence to HBV guidelines was similar or better in HBV-HIV versus HBV-M, including HBV treatment (97% vs 71%), biannual hepatocellular carcinoma (HCC) surveillance (55% vs 55%) for patients with cirrhosis, hepatitis A virus screening (69% vs 56%), hepatitis C virus screening (100% vs 99%), and on-therapy alanine aminotransferase monitoring (95% vs 96%). Compared with those seeing gastroenterology (GI) or infectious diseases (ID) providers, patients without specialty care were less likely to receive antiviral treatment (none, 39%; GI, 80%; ID, 84%) or HCC surveillance (none, 16%; GI, 66%; ID, 47%). These findings persisted in multivariable analysis. Compared with ID care alone, a higher proportion of patients with HBV-HIV seen dually by GI and ID received HCC surveillance (GI + ID 73% vs ID 31%) and on-therapy HBV-DNA monitoring (GI + ID, 82%; ID, 68%). CONCLUSIONS: Patients with HBV-HIV received similar or higher rates of guideline-adherent HBV-related care than patients with HBV-M. Patients with HBV-HIV under dual GI and ID care achieved higher quality care compared with ID care alone. Specialty care was independently associated with higher quality HBV care in patients with HBV-HIV and HBV-M.

Risk factors for adverse outcomes in emergency versus nonemergency open umbilical hernia repair and opportunities for elective repair in a national cohort of patients with cirrhosis.

BACKGROUND: Whether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair. METHODS: Veterans diagnosed with cirrhosis between 2001 and 2014 and a frequency-matched sample of veterans without cirrhosis were followed through September 2017. Veterans Affairs Surgical Quality Improvement Program data provided outcomes and risk factors for mortality after umbilical hernia repair. We performed chart review of a random sample of patients undergoing emergency umbilical hernia repair. RESULTS: Among 119,605 veterans with cirrhosis and 118,125 matched veterans without cirrhosis, the Veterans Affairs Surgical Quality Improvement Program database included 1,475 and 552 open umbilical hernia repairs, respectively. In patients with cirrhosis, 30-day mortality was 1.2% after nonemergency umbilical hernia repair and 12.2% after emergency umbilical hernia repair, contrasting with zero deaths in patients without cirrhosis undergoing these repairs. In patients with cirrhosis but no ascites in the prior month, 30-day mortality after nonemergency umbilical hernia repair was 0.7%, compared to 2.2% in those with ascites. Chart review of patients requiring emergency umbilical hernia repair revealed that elective umbilical hernia repair may have been feasible in 30% of these patients in the prior year; fewer than half of those undergoing emergency umbilical hernia repair had received a general surgery consultation in the prior 2 years. CONCLUSIONS: Nonemergency open umbilical hernia repair was associated with relatively low perioperative mortality in patients with cirrhosis and no recent ascites. About 30% of patients undergoing emergency umbilical hernia repair may have been candidates for nonemergency repair in the prior year.

A Machine Learning Model to Successfully Predict Future Diagnosis of Chronic Myelogenous Leukemia With Retrospective Electronic Health Records Data.

BACKGROUND: Chronic myelogenous leukemia (CML) is a clonal stem cell disorder accounting for 15% of adult leukemias. We aimed to determine if machine learning models could predict CML using blood cell counts prior to diagnosis. METHODS: We identified patients with a diagnostic test for CML (BCR-ABL1) and at least 6 consecutive prior years of differential blood cell counts between 1999 and 2020 in the largest integrated health care system in the United States. Blood cell counts from different time periods prior to CML diagnostic testing were used to train, validate, and test machine learning models. RESULTS: The sample included 1,623 patients with BCR-ABL1 positivity rate 6.2%. The predictive ability of machine learning models improved when trained with blood cell counts closer to time of diagnosis: 2 to 5 years area under the curve (AUC), 0.59 to 0.67, 0.5 to 1 years AUC, 0.75 to 0.80, at diagnosis AUC, 0.87 to 0.92. CONCLUSIONS: Blood cell counts collected up to 5 years prior to diagnostic workup of CML successfully predicted the BCR-ABL1 test result. These findings suggest a machine learning model trained with blood cell counts could lead to diagnosis of CML earlier in the disease course compared to usual medical care.

The Hepatic Innovation Team Collaborative: A Successful Population-Based Approach to Hepatocellular Carcinoma Surveillance.

After implementing a successful hepatitis C elimination program, the Veterans Health Administration's (VHA) Hepatic Innovation Team (HIT) Collaborative pivoted to focus on improving cirrhosis care. This national program developed teams of providers across the country and engaged them in using systems redesign methods and population health approaches to improve care. The HIT Collaborative developed an Advanced Liver Disease (ALD) Dashboard to identify Veterans with cirrhosis who were due for surveillance for hepatocellular carcinoma (HCC) and other liver care, promoted the use of an HCC Clinical Reminder in the electronic health record, and provided training and networking opportunities. This evaluation aimed to describe the VHA's approach to improving cirrhosis care and identify the facility factors and HIT activities associated with HCC surveillance rates, using a quasi-experimental design. Across all VHA facilities, as the HIT focused on cirrhosis between 2018-2019, HCC surveillance rates increased from 46% (IQR 37-53%) to 51% (IQR 42-60%, p < 0.001). The median HCC surveillance rate was 57% in facilities with high ALD Dashboard utilization compared with 45% in facilities with lower utilization (p < 0.001) and 58% in facilities using the HCC Clinical Reminder compared with 47% in facilities not using this tool (p < 0.001) in FY19. Increased use of the ALD Dashboard and adoption of the HCC Clinical Reminder were independently, significantly associated with HCC surveillance rates in multivariate models, controlling for other facility characteristics. In conclusion, the VHA's HIT Collaborative is a national healthcare initiative associated with significant improvement in HCC surveillance rates.

Incidence and Risk Factors of Postoperative Mortality and Morbidity After Elective Versus Emergent Abdominal Surgery in a National Sample of 8193 Patients With Cirrhosis.

OBJECTIVE: To describe the incidence and risk factors for mortality and morbidity in patients with cirrhosis undergoing elective or emergent abdominal surgeries. BACKGROUND: Postoperative morbidity and mortality are higher in patients with cirrhosis; variation by surgical procedure type and cirrhosis severity remain unclear. METHODS: We analyzed prospectively-collected data from the Veterans Affairs (VA) Surgical Quality Improvement Program for 8193 patients with cirrhosis, 864 noncirrhotic controls with chronic hepatitis B infection, and 5468 noncirrhotic controls without chronic liver disease, who underwent abdominal surgery from 2001 to 2017. Data were analyzed using random-effects models controlling for potential confounders. RESULTS: Patients with cirrhosis had significantly higher 30-day mortality than noncirrhotic patients with chronic hepatitis B [4.4% vs 1.3%, adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.57-4.98] or with no chronic liver disease (0.8%, aOR 4.68, 95% CI 3.27-6.69); mortality difference was highest in patients with Model for End-stage Liver Disease (MELD) score ≥10. Among patients with cirrhosis, postoperative mortality was almost 6 times higher after emergent rather than elective surgery (17.2% vs. 2.1%, aOR 5.82, 95% CI 4.66-7.27). For elective surgeries, 30-day mortality was highest after colorectal resection (7.0%) and lowest after inguinal hernia repair (0.6%). Predictors of postoperative mortality included cirrhosis-related characteristics (high MELD score, low serum albumin, ascites, encephalopathy), surgery-related characteristics (emergent vs elective, type of surgery, intraoperative blood transfusion), comorbidities (chronic obstructive pulmonary disease, cancer, sepsis, ventilator dependence, functional status), and age. CONCLUSIONS: Accurate preoperative risk assessments in patients with cirrhosis should account for cirrhosis severity, comorbidities, type of procedure, and whether the procedure is emergent versus elective.

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B.

BACKGROUND & AIMS: Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. METHODS: We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. RESULTS: We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). CONCLUSIONS: HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. LAY SUMMARY: Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.

Assessment of a Deep Learning Model to Predict Hepatocellular Carcinoma in Patients With Hepatitis C Cirrhosis.

Importance: Deep learning, a family of machine learning models that use artificial neural networks, has achieved great success at predicting outcomes in nonmedical domains. Objective: To examine whether deep learning recurrent neural network (RNN) models that use raw longitudinal data extracted directly from electronic health records outperform conventional regression models in predicting the risk of developing hepatocellular carcinoma (HCC). Design, Setting, and Participants: This prognostic study included 48 151 patients with hepatitis C virus (HCV)-related cirrhosis in the national Veterans Health Administration who had at least 3 years of follow-up after the diagnosis of cirrhosis. Patients were identified by having at least 1 positive HCV RNA test between January 1, 2000, to January 1, 2016, and were followed up from the diagnosis of cirrhosis to January 1, 2019, for the development of incident HCC. A total of 3 models predicting HCC during a 3-year period were developed and compared, as follows: (1) logistic regression (LR) with cross-sectional inputs (cross-sectional LR); (2) LR with longitudinal inputs (longitudinal LR); and (3) RNN with longitudinal inputs. Data analysis was conducted from April 2018 to August 2020. Exposures: Development of HCC. Main Outcomes and Measures: Area under the receiver operating characteristic curve, area under the precision-recall curve, and Brier score. Results: During a mean (SD) follow-up of 11.6 (5.0) years, 10 741 of 48 151 patients (22.3%) developed HCC (annual incidence, 3.1%), and a total of 52 983 samples (51 948 [98.0%] from men) were collected. Patients who developed HCC within 3 years were older than patients who did not (mean [SD] age, 58.2 [6.6] years vs 56.9 [6.9] years). RNN models had superior mean (SD) area under the receiver operating characteristic curve (0.759 [0.009]) and mean (SD) Brier score (0.136 [0.003]) than cross-sectional LR (0.689 [0.009] and 0.149 [0.003], respectively) and longitudinal LR (0.682 [0.007] and 0.150 [0.003], respectively) models. Using the RNN model, the samples with the mean (SD) highest 51% (1.5%) of HCC risk, in which 80% of all HCCs occurred, or the mean (SD) highest 66% (1.2%) of HCC risk, in which 90% of all HCCs occurred, could potentially be targeted. Among samples from patients who achieved sustained virologic response, the performance of the RNN models was even better (mean [SD] area under receiver operating characteristic curve, 0.806 [0.025]; mean [SD] Brier score, 0.117 [0.007]). Conclusions and Relevance: In this study, deep learning RNN models outperformed conventional LR models, suggesting that RNN models could be used to identify patients with HCV-related cirrhosis with a high risk of developing HCC for risk-based HCC outreach and surveillance strategies.

Effect of travel distance and rurality of residence on initial surveillance for hepatocellular carcinoma in VA primary care patient with cirrhosis.

OBJECTIVE: To determine the relationship between travel distance and surveillance for hepatocellular carcinoma among veterans with cirrhosis. DATA SOURCES: Veterans Health Administration (VHA) inpatient and outpatient administrative data were linked to geocoded enrollee files. CMS-VHA merged data were used to assess receipt of Medicare-financed non-VA imaging. STUDY DESIGN: A retrospective cohort of US veterans diagnosed with cirrhosis between 2009 and 2015 was examined. First available abdominal imaging following the diagnosis of cirrhosis was analyzed separately as a function of travel distance to the nearest VA medical center (VAMC) and to the patient's assigned VA primary care provider. Veterans with dual use of Medicare and VA services were also examined for receipt of imaging outside of the VA. PRINCIPAL FINDINGS: Veterans who resided more than 30 miles from the nearest VAMC were less likely to receive any imaging for HCC surveillance. Among dual users, increased travel distance between the patient's residence and nearest VAMC was associated with an increased likelihood of receiving any abdominal imaging at non-VA facilities. CONCLUSION: Increased travel distance to the nearest VA medical center reduces the likelihood of receiving imaging for HCC surveillance in cirrhotic veterans. Future efforts should focus on reducing geographic barriers to HCC surveillance.

Brief Report: Incidence of HIV in a Nationwide Cohort Receiving Pre-exposure Prophylaxis for HIV Prevention.

BACKGROUND: Cases of HIV, while infrequent, have been reported during tenofovir disoproxil fumarate/emtricitabine use as pre-exposure prophylaxis (PrEP). We describe the incidence of HIV and patterns of PrEP use within the Veterans Health Administration (VHA). METHODS: We conducted a retrospective cohort study among persons initiating PrEP in the VHA between July 2012 and April 2016 using national VHA data. We defined time on PrEP and time at risk of HIV exposure as the total time from the first PrEP fill to exhaustion of supply of the final PrEP prescription. We identified incident cases of HIV infection after PrEP initiation based on laboratory data. Medication adherence measures and days without pills were calculated using pharmacy fill data. We used a chart review to determine patient-reported PrEP use around the time of diagnosis. RESULTS: We identified 825 unique patients initiating PrEP; they were 97% men and 67% white, with a mean age of 41 years. Six HIV infections were observed during the study period, yielding an HIV incidence of 0.8 (Poisson exact 95% confidence interval: 0.3 to 1.8) cases per 100 person-years. Two cases occurred during active PrEP use by self-report and perfect adherence based on fill data. Both were infected with viruses containing the M184V mutation. Four additional cases were diagnosed after self-reported discontinuation. CONCLUSIONS: HIV infection was rare in a nationwide cohort of PrEP users. Although most of the infections occurred during inconsistent PrEP use, infections during periods of high measured adherence were also observed. These findings highlight the importance of PrEP persistence during periods of risk.

Access to Comprehensive Services for Advanced Liver Disease in the Veterans Health Administration.

BACKGROUND: The Veterans Health Administration (VHA) provides care to the one of the largest cohorts of patients with advanced liver disease (ALD) in the USA. AIMS: We performed a national survey to assess system-wide strengths and barriers to care for Veterans with ALD in this national integrated healthcare setting. METHODS: A 52-item survey was developed to assess access and barriers to care in Veterans with ALD. The survey was distributed to all VHA medical centers in 2015. Results were analyzed using descriptive statistics. RESULTS: One hundred and fifty-three sites responded to this survey. Multidisciplinary services were available on-site at > 80% of sites. Ninety-five percent of sites had mental health and addictions treatment available, with 14% co-locating these services within the liver clinic. Few sites (< 25%) provided pharmacologic treatment for alcohol use disorder in primary care or hepatology settings. Seventy-two percent of sites reported at least one barrier to liver-related care. Of the sites reporting at least one barrier, 53% reported barriers to liver transplant referral, citing complex processes and lack of staff/resources to coordinate referrals. Palliative care was widely available, but 61% of sites reported referring < 25% of their patients with ALD for palliative services. CONCLUSION: Multidisciplinary services for Veterans with ALD are widely available at VHA sites, though barriers to optimal care remain. Opportunities for improvement include the expansion of providers with hepatology expertise, integrating pharmacotherapy for alcohol use disorder into hepatology and primary care, streamlining the transplant referral process, and expanding palliative care referrals for patients with ALD.

Increased Risk for Hepatocellular Carcinoma Persists Up to 10 Years After HCV Eradication in Patients With Baseline Cirrhosis or High FIB-4 Scores.

BACKGROUND & AIMS: It is unclear if hepatocellular carcinoma (HCC) risk declines over time after hepatitis C virus (HCV) eradication. We analyzed changes in HCC annual incidence over time following HCV eradication and identified dynamic markers of HCC risk. METHODS: We identified 48,135 patients who initiated HCV antiviral treatment from 2000 through 2015 and achieved a sustained virologic response (SVR) in the Veterans Health Administration (29,033 treated with direct-acting antiviral [DAA] agents and 19,102 treated with interferon-based regimens). Patients were followed after treatment until February 14, 2019 (average 5.4 years), during which 1509 incident HCCs were identified. RESULTS: Among patients with cirrhosis before treatment with DAAs (n = 9784), those with pre-SVR fibrosis-4 (FIB-4) scores ≥3.25 had a higher annual incidence of HCC (3.66%/year) than those with FIB-4 scores <3.25 (1.16%/year) (adjusted hazard ratio 2.14; 95% confidence interval 1.66-2.75). In DAA-treated patients with cirrhosis and FIB-4 scores ≥3.25, annual HCC risk decreased from 3.8%/year in the first year after SVR to 2.4%/year by the fourth year (P=.01). In interferon-treated patients with FIB-4 scores ≥3.25, annual HCC risk remained above 2%/year, even 10 years after SVR. A decrease in FIB-4 scores from ≥3.25 pre-SVR to <3.25 post-SVR was associated with an approximately 50% lower risk of HCC, but the absolute annual risk remained above 2%/year. Patients without cirrhosis before treatment (n = 38,351) had a low risk of HCC, except for those with pre-SVR FIB-4 scores ≥3.25 (HCC risk 1.22%/year) and post-SVR FIB-4 scores ≥3.25 (HCC risk 2.39%/year); risk remained high for many years after SVR. CONCLUSIONS: Patients with cirrhosis before an SVR to treatment for HCV infection continue to have a high risk for HCC (>2%/year) for many years, even if their FIB-4 score decreases, and should continue surveillance. Patients without cirrhosis but with FIB-4 scores ≥3.25 have a high enough risk to merit HCC surveillance, especially if FIB-4 remains ≥3.25 post-SVR.

Quality Measures, All-Cause Mortality, and Health Care Use in a National Cohort of Veterans With Cirrhosis.

Decompensated cirrhosis is associated with high morbidity and mortality. However, no standardized quality measures (QMs) have yet been adopted widely. The Veterans Affairs (VA) Advanced Liver Disease Technical Advisory Group recently developed a set of six internal QMs to guide quality improvement efforts in cirrhosis in the domains of access to care, hepatocellular carcinoma surveillance, variceal surveillance, quality of inpatient care for upper gastrointestinal bleeding, and cirrhosis-related rehospitalizations. We aimed to (1) quantify adherence to cirrhosis QMs and (2) determine whether adherence was associated with all-cause mortality and health care use within a large national cohort of veterans with cirrhosis. We performed a retrospective study using data from the Veterans Outcomes and Costs Asociated with Liver Disease cohort of 121,129 patients newly diagnosed with cirrhosis from January 1, 2008, to December 31, 2016, at 128 VA facilities. The mean follow-up time was 2.7 years (interquartile range, 1.1-5.1 years). Adherence to outpatient access to specialty care was 71%, variceal surveillance was 32%, and early postdischarge care was 54%. In adjusted analyses, outpatient access to specialty care (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.78-0.82), hepatocellular carcinoma surveillance (HR, 0.92; 95% CI, 0.90-0.95), variceal surveillance (HR, 0.93; 95% CI, 0.89-0.99), and early postdischarge care (HR, 0.57; 95% CI, 0.54-0.60) were associated with lower all-cause mortality. Readmissions after 30 days (HR, 1.53; 1.46-1.60) and 90 days (HR, 1.88; 95% CI, 1.54-1.70) were associated with higher all-cause mortality. Higher adherence to QMs was also associated with lower inpatient health care use. Conclusion: Five of the six proposed VA cirrhosis QMs were measurable using existing data sources, associated with mortality and health care use, and may be used to guide future quality improvement efforts in cirrhosis.

Machine learning models to predict disease progression among veterans with hepatitis C virus.

BACKGROUND: Machine learning (ML) algorithms provide effective ways to build prediction models using longitudinal information given their capacity to incorporate numerous predictor variables without compromising the accuracy of the risk prediction. Clinical risk prediction models in chronic hepatitis C virus (CHC) can be challenging due to non-linear nature of disease progression. We developed and compared two ML algorithms to predict cirrhosis development in a large CHC-infected cohort using longitudinal data. METHODS AND FINDINGS: We used national Veterans Health Administration (VHA) data to identify CHC patients in care between 2000-2016. The primary outcome was cirrhosis development ascertained by two consecutive aspartate aminotransferase (AST)-to-platelet ratio indexes (APRIs) > 2 after time zero given the infrequency of liver biopsy in clinical practice and that APRI is a validated non-invasive biomarker of fibrosis in CHC. We excluded those with initial APRI > 2 or pre-existing diagnosis of cirrhosis, hepatocellular carcinoma or hepatic decompensation. Enrollment was defined as the date of the first APRI. Time zero was defined as 2 years after enrollment. Cross-sectional (CS) models used predictors at or closest before time zero as a comparison. Longitudinal models used CS predictors plus longitudinal summary variables (maximum, minimum, maximum of slope, minimum of slope and total variation) between enrollment and time zero. Covariates included demographics, labs, and body mass index. Model performance was evaluated using concordance and area under the receiver operating curve (AuROC). A total of 72,683 individuals with CHC were analyzed with the cohort having a mean age of 52.8, 96.8% male and 53% white. There are 11,616 individuals (16%) who met the primary outcome over a mean follow-up of 7 years. We found superior predictive performance for the longitudinal Cox model compared to the CS Cox model (concordance 0.764 vs 0.746), and for the longitudinal boosted-survival-tree model compared to the linear Cox model (concordance 0.774 vs 0.764). The accuracy of the longitudinal models at 1,3,5 years after time zero also showed superior performance compared to the CS model, based on AuROC. CONCLUSIONS: Boosted-survival-tree based models using longitudinal information are statistically superior to cross-sectional or linear models for predicting development of cirrhosis in CHC, though all four models were highly accurate. Similar statistical methods could be applied to predict outcomes in other non-linear chronic disease states.

Health Care Facility Characteristics are Associated with Variation in Human Immunodeficiency Virus Pre-exposure Prophylaxis Initiation in Veteran's Health Administration.

To quantify health care facility-level variation in pre-exposure prophylaxis (PrEP) use in the Veteran's Health Administration (VHA); to identify facility characteristics associated with PrEP use. Retrospective analysis of the health care facility-level rate of PrEP initiation in VHA through June 30, 2017. Standardized PrEP initiation rates were used to rank facilities. Characteristics of facilities, prescribers, and PrEP recipients were examined within quartiles. Multiple linear regression was used to identify associations between facility characteristics and PrEP use. We identified 1600 PrEP recipients. Mean PrEP initiation rate was 20.0/100,000 (SD 22.8), ranging from 3.0/100,000 (SD 2.0) in the lowest quartile to 48.1/100,000 (SD 29.1) in the highest. PrEP prescribing was positively associated with proportions of urban dwellers and individuals < 45, tertiary care status, and location. Variability in PrEP uptake across a national health care system highlights opportunities to expand access in non-tertiary care facilities and underserved areas.

Characteristics of Opioid Prescriptions to Veterans With Cirrhosis.

BACKGROUND & AIMS: Despite increased risks for adverse effects in patients with cirrhosis, little is known about opioid prescriptions for this population. We aimed to assess time trends in opioid prescribing and factors associated with receiving opioids among patients with cirrhosis. METHODS: Among Veterans with cirrhosis, identified using national Veterans Health Administration data (2005-2014), we assessed characteristics of patients and their prescriptions for opioids. We calculated the annual proportion of patients receiving any opioid prescription. Among opioid recipients, we assessed prescriptions that were long-term (>90 days' supply), for high doses (>100 MME/day), or involved combinations of opioids and acetaminophen or benzodiazepine. We evaluated patient characteristics independently associated with long-term and any opioid prescriptions using mixed-effects regression models. RESULTS: Among 127,239 Veterans with cirrhosis, 97,974 (77.0%) received a prescription for an opioid. Annual opioid prescriptions increased from 36% in 2005 to 47% in 2014 (P < .01). Among recipients of opioids, the proportions of those receiving long-term prescriptions increased from 47% in 2005 to 54% in 2014 (P < .01), and19%-21% received prescriptions for high-dose opioids. Prescriptions for combinations of opioids and acetaminophen decreased from 68% in 2005 to 50% in 2014 (P < .01) and for combinations of opioids and benzodiazepines decreased from 24% to 19% over this time (P < .01). Greater probability of long-term opioid prescriptions was independently associated with younger age, female sex, white race, hepatitis C, prior hepatic decompensation, hepatocellular carcinoma, mental health disorders, nicotine use disorders, medical comorbidities, surgery, and pain-related conditions. CONCLUSION: Among Veterans with cirrhosis, 36%-47% were prescribed opioids in each year. Mental health disorders and hepatic decompensation were independently associated with long-term opioid prescriptions.

Preventing Hepatitis B Reactivation During Anti-CD20 Antibody Treatment in the Veterans Health Administration.

Hepatitis B virus (HBV) reactivation may occur with high risk immunosuppression, such as anti-cluster of differentiation (CD)20 antibodies (Abs). Appropriate HBV prophylaxis during anti-CD20 Ab therapy averts hepatitis, chemotherapy disruption, and death. Serologic evidence of prior HBV exposure is present in one in nine veterans in the Veterans Health Administration (VHA). In 2014, most (61%-73%) patients in the VHA who were receiving anti-CD20 Ab treatment underwent HBV testing, yet <20% of eligible patients received HBV antiviral prophylaxis. We aimed to prevent HBV reactivation by increasing HBV testing and antiviral treatment rates among anti-CD20 Ab recipients through prospective interventions. A multidisciplinary team of clinicians, pharmacists, and public health professionals developed comprehensive prevention systems, including national seminars/newsletters/websites; pharmacy criteria for HBV screening/treatment prior to anti-CD20 Ab use; changes to national formulary restrictions to expand HBV prophylaxis prescribing authority; Medication Use Evaluation Tracker to identify omissions; national e-mail alert to all VHA oncology providers detailing specific testing and HBV antiviral treatment needs; and a voluntary electronic medical record "order check" used at interested facilities (n = 11) to automatically assess pretreatment HBV testing and antiviral treatment and only generate a reminder to address deficiencies. Analysis of monthly data from June 2016 through September 2017 among anti-CD20 Ab recipients revealed pre-anti-CD20 Ab treatment HBV testing increased to 91%-96% and appropriate HBV antiviral prophylaxis to 76%-85% nationally following implementation of the intervention. Medical centers using the voluntary electronic medical record order check increased HBV testing rates to 93%-98% and HBV antiviral prophylaxis rates to 99%. Conclusion: Multimodal intervention systems to prevent HBV reactivation among VHA patients receiving anti-CD20 Ab therapies increased national rates of HBV testing to >90% and antiviral prophylaxis to >80%.

Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for hepatitis C.

BACKGROUND & AIMS: Most patients with hepatitis C virus (HCV) infection will undergo antiviral treatment with direct-acting antivirals (DAAs) and achieve sustained virologic response (SVR). We aimed to develop models estimating hepatocellular carcinoma (HCC) risk after antiviral treatment. METHODS: We identified 45,810 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1/1/2009 to 12/31/2015, including 29,309 (64%) DAA-only regimens and 16,501 (36%) interferon ±â€¯DAA regimens. We retrospectively followed patients until 6/15/2017 to identify incident cases of HCC. We used Cox proportional hazards regression to develop and internally validate models predicting HCC risk using baseline characteristics at the time of antiviral treatment. RESULTS: We identified 1,412 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 2.5 years (range 1.0-7.5 years). Models predicting HCC risk after antiviral treatment were developed and validated separately for four subgroups of patients: cirrhosis/SVR, cirrhosis/no SVR, no cirrhosis/SVR, no cirrhosis/no SVR. Four predictors (age, platelet count, serum aspartate aminotransferase/√alanine aminotransferase ratio and albumin) accounted for most of the models' predictive value, with smaller contributions from sex, race-ethnicity, HCV genotype, body mass index, hemoglobin and serum alpha-fetoprotein. Fitted models were well-calibrated with very good measures of discrimination. Decision curves demonstrated higher net benefit of using model-based HCC risk estimates to determine whether to recommend screening or not compared to the screen-all or screen-none strategies. CONCLUSIONS: We developed and internally validated models that estimate HCC risk following antiviral treatment. These models are available as web-based tools that can be used to inform risk-based HCC surveillance strategies in individual patients. LAY SUMMARY: Most patients with hepatitis C virus have been treated or will be treated with direct-acting antivirals. It is important that we can model the risk of hepatocellular carcinoma in these patients, so that we develop the optimum screening strategy that avoids unnecessary screening, while adequately screening those at increased risk. Herein, we have developed and validated models that are available as web-based tools that can be used to guide screening strategies.