Utility of learning ratio scores from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Memory Test in distinguishing patterns of cognitive decline in veterans referred for neuropsychological evaluation.

Background: The Learning Ratio (LR) is a novel learning score that has shown improved utility over other learning metrics in detecting Alzheimer's disease (AD) across multiple memory tasks. However, its utility on the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD WLMT), a widely used list learning measure sensitive to decline in neurodegenerative disease, is unknown. The goal of the current study was to determine the utility of LR on the CERAD WLMT in differentiating between diagnostic (MiNCD vs MaNCD) and etiologic groups (VaD vs AD) in a veteran sample. Methods: Raw learning slope (RLS) and LR scores were examined in 168 veterans diagnosed with major neurocognitive disorder (MaNCD), mild neurocognitive disorder (MiNCD), or normal aging following neuropsychological evaluation. Patients with MaNCD were further classified by suspected etiology (i.e. microvascular disease vs AD). Results: Whereas RLS scores were not significantly different between MiNCD and MaNCD, LR scores were significantly different between all diagnostic groups (p's < .05). Those with AD had lower LR scores and RLS scores compared to those with VaD (p's < .05). LR classification accuracy was acceptable for MiNCD (AUC = .76), excellent for MaNCD (AUC = .86) and VaD (AUC = .81), and outstanding for AD (AUC = .91). Optimal cutoff scores for WLMT LR were derived from Youden's index. Conclusion: Results support the use of LR scores over RLS when interpreting the CERAD WLMT and highlight the clinical utility of LR in differentiating between diagnostic groups and identifying suspected etiology.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Medication use and comorbidities in an increasingly younger osteoarthritis population: an 18-year retrospective open-cohort study.

OBJECTIVES: As understanding of the pathogenesis and treatment strategies for osteoarthritis (OA) evolves, it is important to understand how patient factors are also changing. Our goal was to examine demographics and known risk factors of patients with OA over time. DESIGN: Open-cohort retrospective study using electronic health records. SETTING: Large US integrated health system with 7 hospitals, 2.6 million outpatient clinic visits and 97 300 hospital admissions annually in a mostly rural geographic region. PARTICIPANTS: Adult patients with at least two encounters and a diagnosis of OA or OA-relevant surgery between 2001 and 2018. Because of geographic region, over 96% of participants were white/Caucasian. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive statistics were used to examine age, sex, body mass index (BMI), Charlson Comorbidity Index, major comorbidities and OA-relevant prescribing over time. RESULTS: We identified 290 897 patients with OA. Prevalence of OA increased significantly from 6.7% to 33.5% and incidence increased 37% (from 3772 to 5142 new cases per 100 000 patients per year) (p<0.0001). Percentage of females declined from 65.3% to 60.8%, and percentage of patients with OA in the youngest age bracket (18-45 years) increased significantly (6.2% to 22.7%, p<0.0001). The percentage of patients with OA with BMI ≥30 remained above 50% over the time period. Patients had low comorbidity overall, but anxiety, depression and gastro-oesophageal reflux disease showed the largest increases in prevalence. Opioid use (tramadol and non-tramadol) showed peaks followed by declines, while most other medications increased slightly in use or remained steady. CONCLUSIONS: We observe increasing OA prevalence and a greater proportion of younger patients over time. With better understanding of how characteristics of patients with OA are changing over time, we can develop better approaches for managing disease burden in the future.

Impact of hepatitis C treatment status on risk of Parkinson's disease and secondary parkinsonism in the era of direct-acting antivirals.

Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.

Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States.

The epidemiology of latent tuberculosis and hepatitis B virus (HBV-LTBI) co-infection among U.S. populations is not well studied. We aim to evaluate LTBI testing patterns and LTBI prevalence among two large U.S. cohorts of adults with chronic HBV (CHB). Adults with CHB in the Chronic Hepatitis Cohort Study (CHeCS) and Veterans Affairs national cohort were included in the analyses. Prevalence of HBV-LTBI co-infection was defined as the number of HBV patients with LTBI divided by the number of HBV patients in a cohort. Multivariable logistic regression evaluated odds of HBV-LTBI co-infection among CHB patients who underwent TB testing. Among 6019 CHB patients in the CHeCS cohort (44% female, 47% Asian), 9.1% were tested for TB, among whom 7.7% had HBV-LTBI co-infection. Among HBV-LTBI co-infected patient, only 16.7% (n = 7) received LTBI treatment, among whom 28.6% (n = 2) developed DILI. Among 12,928 CHB patients in the VA cohort (94% male, 42% African American, 39% non-Hispanic white), 14.7% were tested for TB, among whom 14.5% had HBV-LTBI. Among HBV-LTBI co-infected patient, 18.6% (n = 51) received LTBI treatment, among whom 3.9% (n = 3) developed DILI. Presence of cirrhosis, race/ethnicity, and country of birth were observed to be associated with odds of HBV-LTBI co-infection among CHB patients who received TB testing. In summary, among two large distinct U.S. cohorts of adults with CHB, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI co-infection. Moreover, low rates of LTBI treatment were observed among those with HBV-LTBI co-infection.

The association between buprenorphine treatment duration and mortality: a multi-site cohort study of people who discontinued treatment.

BACKGROUND AND AIMS: Buprenorphine is an effective medication for opioid use disorder that reduces mortality; however, many patients are not retained in buprenorphine treatment, and an optimal length of treatment after which patients can safely discontinue treatment has not been identified. This study measured the association between buprenorphine treatment duration and all-cause mortality among patients who discontinued treatment. Secondary objectives were to measure the association between treatment duration and drug overdose and opioid-related overdoses. DESIGN: Multi-site cohort study. SETTING: Eight US health systems. PARTICIPANTS: Patients who initiated and discontinued buprenorphine treatment between 1 January 2012 and 31 December 2018 (n = 6550). Outcomes occurring after patients discontinued buprenorphine treatment were compared between patients who initiated and discontinued treatment after 8-30, 31-90, 91-180, 181-365 and > 365 days. MEASUREMENTS: Covariate data were obtained from electronic health records (EHRs). Mortality outcomes were derived from EHRs and state vital statistics. Non-fatal opioid and drug overdoses were obtained from diagnostic codes. Four sites provided cause-of-death data to identify fatal drug and opioid-related overdoses. Adjusted frailty regression was conducted on a propensity-weighted cohort to assess associations between duration of the final treatment episode and outcomes. FINDINGS: The mortality rate after buprenorphine treatment was 1.82 per 100 person-years (n = 191 deaths). In regression analyses with > 365 days as the reference group, treatment duration was not associated with all-cause mortality and drug overdose (P > 0.05 for both). However, compared with > 365 days of treatment, 91-180 days of treatment was associated with increased opioid overdose risk (hazard ratio = 2.94, 95% confidence interval = 1.11-7.79). CONCLUSIONS: Among patients who discontinue buprenorphine treatment, there appears to be no treatment duration period associated with a reduced risk for all-cause mortality. Patients who discontinue buprenorphine treatment after 91-180 days appear to be at heightened risk for opioid overdose compared with patients who discontinue after > 365 days of treatment.

Validation and extension of the quick dementia rating system (QDRS).

Informant report dementia severity staging measures, such as the Quick Dementia Rating System (QDRS) offer clinicians useful diagnostic and staging information. These measures also potentially avoid many of the pitfalls inherent in mental status examinations (e.g., cultural bias, educational bias, floor and ceiling effects). We derive cut points for the QDRS and comprehensively examine their classification accuracy in a large, diagnostically heterogeneous, rural, memory disorder clinic sample. Our findings suggest the QDRS may be helpful when used in the context of a comprehensive diagnostic and staging evaluation. When used in isolation, the QDRS is insufficiently accurate for diagnosis and staging of dementia.

Impact and Risk of Moral Injury Among Deployed Veterans: Implications for Veterans and Mental Health.

The impact of "moral injury" (MI) among deployed veterans, defined as actions in combat that violate a veteran's moral beliefs and result in psychological distress, has increasingly become a significant clinical concern separate from other trauma- and stressor-related disorders. MI involves severe distress over violations of core beliefs often followed by feelings of guilt and conflict and is common among veterans with PTSD. While the psychological impact of PTSD is well-documented among veterans, this has been done less so with respect to MI. We studied MI among 1,032 deployed veterans who were outpatients in a large non-profit multi-hospital system in central Pennsylvania. The study included active duty and Guard/Reserve members, as well as veterans who were not Department of Veterans Affairs (VA) service users. Our hypothesis was that, controlling for other risk factors, veterans with high MI would have current mental disorders. Our secondary hypothesis was that MI would be associated with other psychopathologies, including chronic pain, sleep disorders, fear of death, anomie, and use of alcohol/drugs to cope post deployment. Most veterans studied were deployed to Vietnam (64.1%), while others were deployed to post-Vietnam conflicts in Iraq and Afghanistan and elsewhere. Altogether, 95.1% of the veterans were male and their mean age was 61.6 years (SD = 11.8). Among the veterans, 24.4% had high combat exposure, 10.9% had PTSD, 19.8% had major depressive disorder, and 11.7% had a history of suicidal thoughts. Based on the Moral Injury Events Scale (MIES), 25.8% had high MI post deployment, defined as a score above the 75th percentile. Results show that high MI among veterans was associated with current global mental health severity and recent mental health service use, but not suicidal thoughts. In addition, as hypothesized, MI was also associated with pain, sleep disorders, fear of death, anomie, use of alcohol/drugs to cope post-deployment, and poor unit support/morale during deployment. Deployed veterans with MI are more likely to have current mental health disorders and other psychological problems years after deployment. Further research is advised related to the screening, assessment, treatment, and prevention of MI among veterans and others after trauma exposures.

Development and implementation of a prescription opioid registry across diverse health systems.

Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.

Associations of Healthcare Utilization and Costs with Increasing Pain and Treatment Intensity Levels in Osteoarthritis Patients: An 18-Year Retrospective Study.

INTRODUCTION: Osteoarthritis (OA) is a complex disease, and prior studies have documented the health and economic burdens of patients with OA compared to those without OA. Our goal was to use two strategies to further stratify OA patients based on both pain and treatment intensity to examine healthcare utilization and costs using electronic records from 2001 to 2018 at a large integrated health system. METHODS: Adult patients with ≥1 pain numerical rating scale (NRS) and diagnosis of OA were included. Pain episodes of ≥90 days were defined as mild (0-3), moderate (4-6), or severe (7-10) based on initial NRS. Patients were initially classified as mild and moved to moderate-severe OA if any of eight treatment-based criteria were met. Outpatient visits (OP), emergency department visits (ED), inpatient days, and healthcare costs (both all-cause and OA-specific) were compared among pain levels and OA severity levels as frequencies and per-member-per-year rates, using generalized linear regression models adjusting for age, sex, and body mass index, with contrasts of p < 0.05 considered significant. RESULTS: We identified 127,656 patients, 92,576 with pain scores. Moderate and severe pain were associated with significantly higher rates of OA-related utilization and costs, and all-cause ED visits and pharmacy costs. Moderate-severe OA patients had significantly higher OA-related utilization and costs, and all-cause OP, ED and pharmacy costs. CONCLUSIONS: Pain and treatment intensity were both strongly associated with OA-related utilization but not consistently with all-cause utilization. Our results provide promising evidence of better criteria and approaches for predicting disease burden and costs in the future.

Lower Rates of Emergency Department Visits and Hospitalizations Among Patients With Chronic Hepatitis C With Sustained Virological Response to Interferon-Free Direct-Acting Antiviral Therapy (2014-2018).

We compared rates of emergency department visits and hospitalizations between patients with hepatitis C virus who achieved sustained virological response after direct-acting antiviral therapy (case patients) and matched controls. Among 3049 pairs, case patients demonstrated lower rates of liver-related emergency department visits (P = .01) than controls; all-cause and liver-related hospitalization rates and number of hospitalized days were also lower in case patients (P < .001).

Genetic and Psychosocial Risk Factors Associated with Suicide Among Community Veterans: Implications for Screening, Treatment and Precision Medicine.

INTRODUCTION: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans. METHODS: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0-8, mean=3.6, SD=1.4). RESULTS: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p<0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p<0.001), history of depression (p>0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant. DISCUSSION: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.

Incidence of Malignancies Among Patients With Chronic Hepatitis B in US Health Care Organizations, 2006-2018.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Predicting adolescent alcohol and other drug problems using electronic health records data.

IMPORTANCE: Alcohol and other drug (AOD) use problems may cause significant burden on affected adolescents and their families, yet treatment providers often do not identify these problems early enough. OBJECTIVE: To develop, and internally and externally validate a multivariable prediction model of adolescent AOD problems using child- and maternal-level predictors before age 12, and child-level predictors between ages 12 to 18, as recorded in the electronic health records (EHR). DESIGN: A retrospective cohort study conducted time-to-event analyses using Cox proportional hazards models. SETTING AND PARTICIPANTS: 41,172 children born between 1997 and 2000 at four health plans (Kaiser Permanente Hawaii, KPHI; Kaiser Permanente Northern California, KPNC; Geisinger Clinic, GC; and Henry Ford Health System, HFHS) who had continuous membership since birth and linkable maternal records in the health plan. OUTCOMES: AOD use problems between ages 12 to 18, defined as either: 1) having a contact with the AOD treatment program or 2) receiving a non-tobacco AOD diagnosis in an inpatient or outpatient encounter. EXPOSURES: Candidate predictor variables include demographics, socioeconomic status, and clinical diagnoses of the children and the mothers. RESULTS: Overall, 1400 (3.4%) adolescents had an AOD disorder between ages 12 to 18; the median follow-up time post-age 12 was 5.3 years. The research team developed two final prediction models: a "baseline" model of 10 child-level and 7 maternal-level predictors before age 12, and a more comprehensive "time-varying" model, which incorporated child risk factors after age 12 as time-varying covariates in addition to the baseline model predictors. Model performance evaluation showed good discrimination performance of the models, with the concordance index improved for the time-varying model, especially for prediction of AOD events in late adolescence. CONCLUSIONS AND RELEVANCE: This study identified a number of child and maternal characteristics and diagnoses routinely available in EHR data as predictive of risk for developing AOD problems in adolescence. Further, we found that risk of developing problems varies significantly by the timing and persistence of the risk factors. Findings may have potential clinical implications for prevention and identification of adolescent AOD problems, but more research is needed, especially across additional health systems.

Psychological well-being and alcohol misuse among community-based veterans: results from the Veterans' Health Study.

BACKGROUND: Maladaptive drinking is an increasing concern among military policy makers and healthcare providers. The goal of this study was to assess how social and psychological factors relate to alcohol problems among post-deployed US veterans and how problematic drinking is associated with well-being. METHODS: Data were collected via a telephone survey from a random sample of veterans receiving their healthcare from a large non-VA hospital system in central Pennsylvania (N = 1730). Interviewers inquired about participants' current alcohol consumption, using the CAGE and AUDIT-C scales, and health-related outcomes (general psychological distress, major depression, and self-reported health status). Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). RESULTS: Analyses included demographic, military and nonmilitary stressful events, use of alcohol or drugs to cope post-deployment, use of psychiatric services, and personality characteristics as independent variables. Our sample was 95% male, 96% White, and had a mean age of 59 years old (SD = 12 years). Analyses for our drinking measures show that those who used drugs or alcohol to cope post-deployment were more likely to be problematic drinkers, while positive personality characteristics such as agreeableness and conscientiousness were related to fewer drinking problems. Multivariate logistic regressions for our well-being measures found that alcohol misuse was not related to distress or depression, but that a positive score on the AUDIT-C was associated with a lower likelihood of poor self-rated health. Using alcohol or drugs to cope was related to higher distress. DISCUSSION: We conclude that service providers might consider using post-deployment AUDIT-C and the drugs and alcohol coping questions when screening for possible alcohol and mental health problems among veterans.

Dynamic Risk Prediction of Response to Ursodeoxycholic Acid Among Patients with Primary Biliary Cholangitis in the USA.

BACKGROUND: Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. METHODS: Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. RESULTS: Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. CONCLUSIONS: Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.

Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016).

BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.

Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States.

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.

Psychosocial Obstacles to Hepatitis C Treatment Initiation Among Patients in Care: A Hitch in the Cascade of Cure.

There are limited data examining the relationship between psychosocial factors and receipt of direct-acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health-related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017-2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow-up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life-related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow-up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion: In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C-related morbidity and mortality.

The Persistence of Underreporting of Hepatitis C as an Underlying or Contributing Cause of Death, 2011-2017.

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden.