BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States (US). RSV immunization, in the form of a monoclonal antibody (mAb) for infants and vaccines for pregnant people, may reduce infant RSV risk. METHODS: In April and May 2023, we surveyed adults with children in Oregon and Washington about the likelihood to accept infant mAb and maternal RSV vaccine and RSV awareness. We used multivariable logistic regression to identify predictors of self-reported likelihood of accepting RSV immunization. RESULTS: Among 1082 respondents, 68% and 70% responded they would very likely accept infant mAb or maternal RSV vaccine, respectively. Respondents had lower odds of accepting infant mAb (OR: 0.10, 95% CI: 0.07-0.15) and maternal RSV vaccine (OR: 0.16, 95% CI: 0.12-0.23) if they were somewhat or very concerned about side effects. Respondents had higher odds of accepting infant mAb if they received an influenza vaccination (OR: 3.79, 95% CI: 1.88-7.63). Respondents had higher odds of accepting maternal vaccine if they had an advanced degree (OR: 1.70, 95% CI: 1.06-2.73), had received an influenza vaccination (OR: 3.62, 95% CI: 1.80-7.25), or were aware of RSV before our survey (OR: 2.03, 95% CI: 1.03-4.01). CONCLUSION: Most respondents reported that they would likely accept RSV mAb for their infant or an RSV vaccine during pregnancy. Concerns about side effects lowered the odds of accepting immunization, however, nearly one-half of those concerned about side effects still expressed a high likelihood of accepting either immunization.

BACKGROUND: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. METHODS: We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. RESULTS: Among 3,344 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 12.3-55.7%) within 7-59 days of vaccination and 21.1% (95% CI: -0.5-37.1%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose ≥180 days prior. Overall, adjusted VE of bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI: 46.0-74.5%) within 7-179 days of vaccination and 39.4% (95% CI: 12.5-61.6%) ≥180 days compared to naïve participants who were unvaccinated/received a monovalent vaccine dose ≥180 days prior. CONCLUSIONS: Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

We conducted a large surveillance study among members of an integrated healthcare delivery system in Pacific Northwest of the United States to estimate medical costs attributable to medically attended acute gastroenteritis (MAAGE) on the day care was sought and during 30-day follow-up. We used multivariable regression to compare costs of MAAGE and non-MAAGE cases matched on age, gender, and index time. Differences accounted for confounders, including race, ethnicity, and history of chronic underlying conditions. Analyses included 73,140 MAAGE episodes from adults and 18,617 from children who were Kaiser Permanente Northwest members during 2014-2016. Total costs were higher for MAAGE cases relative to non-MAAGE comparators as were costs on the day care was sought and costs during follow-up. Costs of MAAGE are substantial relative to the cost of usual-care medical services, and much of the burden accrues during short-term follow-up.

BACKGROUND: Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. METHODS: We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. RESULTS: In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). CONCLUSIONS: Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.

BACKGROUND: While enteric viruses are highly transmissible, household factors associated with transmission are less well documented. We identified individual- and household-level factors associated with viral acute gastroenteritis (AGE) transmission in a large health care network in the United States. METHODS: Patients presenting with AGE were enrolled from April 2014 to September 2016. Patients and symptomatic household members were interviewed, and stool specimens were collected and tested for viral pathogens. Within a household, primary cases were those with the earliest symptom onset and a positive viral test result; secondary cases were household contacts (HHCs) with symptom onset 1-7 days from the primary case onset. Transmission households had at least 1 secondary case. RESULTS: Our analysis included 570 primary cases with 1479 HHCs. The overall secondary attack rate was 23%. HHCs were likely to become secondary cases (n = 338) if they were <5 years old (adjusted odds ratio [aOR], 1.8; 95% CI, 1.2-2.6). Secondary transmission was likely to occur if the primary case was aged <5 years (aOR, 2.2; 95% CI, 1.4-3.6) or 5 to 17 years (aOR, 3.3; 95% CI, 1.9-5.7), was norovirus positive (aOR, 2.7; 95% CI, 1.9-3.7), had a diapered contact (aOR: 2.2, 95% CI: 1.6-3.2), or reported symptoms for >4 days (aOR, 1.5; 95% CI, 1.1-2.1). Households with ≥3 members (aOR, 2.1; 95% CI, 1.1-4.5) were more likely to experience transmission. DISCUSSION: Risk of AGE transmission within households increased if the primary case was younger, was norovirus positive, had a longer symptom duration, or had a diapered contact. Targeted prevention messaging around appropriate cleaning, disinfection, and isolation of persons with AGE should be encouraged.

BACKGROUND: In the United States, public health surveillance systems often underestimate the burden of acute gastroenteritis (AGE) because they only identify disease among those who interact with the healthcare system. OBJECTIVE: To identify factors associated with healthcare-seeking behavior among individuals experiencing community-acquired AGE. METHODS: From October 2016 -September 2017, we conducted a weekly, age-stratified, random sample of Kaiser Permanente Northwest members located in northwest Oregon and southwest Washington, United States. Individuals who completed the online survey and experienced AGE were included in the analysis. Univariate and multivariable logistic regressions were performed to identify predictors of healthcare-seeking behavior. RESULTS: Of the 3,894 survey respondents, 395 experienced an AGE episode and were eligible for analysis, of whom, 82 (21%) sought care for their AGE episode. In the final multivariable model, individuals with a concurrent fever (odds ratio [OR]: 4.76, 95% confidence interval [95% CI]: 2.48-9.13), increased diarrhea duration (≥6 days vs 1-4 days, OR: 4.22, 95% CI: 1.78-10.03), or increased vomiting duration (≥3 days vs 1 days, OR: 2.97, 95% CI: 1.22-7.26), were significantly more likely to seek healthcare. In the adjusted model, no sociodemographic or chronic disease variables were associated with healthcare-seeking behavior. CONCLUSION: These findings suggest that individuals with a short duration of AGE and those without concurrent fever are underrepresented in healthcare facility-based surveillance systems.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: With the potential impact of the COVID-19 pandemic on HIV preexposure prophylaxis (PrEP) care management, we assessed the number of PrEP users and sexually transmitted infection (STI) testing-eligible PrEP users, STI testing rates, and prevalence between prepandemic (January 1, 2018-March 31, 2020) and early-pandemic (April 1, 2020-September 30, 2020) periods. METHODS: In this retrospective cohort study, a PrEP user for a given quarter is defined as either a previous PrEP user or a PrEP initiator who has at least 1-day coverage of tenofovir/emtricitabine in the given quarter. The STI testing-eligible PrEP users for a given quarter were defined as those persons whose runout date (previous dispense date + days of tenofovir/emtricitabine supply) was in the given quarter. RESULTS: The quarterly number of PrEP users increased from the first quarter of 2018 to the first quarter of 2020 and then decreased in the second and third quarter of 2020. Among STI testing-eligible PrEP users who had ≤14 days between runout and next refill date, gonorrhea and chlamydia screening testing rates were 95.1% for prepandemic and 93.4% for early pandemic ( P = 0.1011). Among all STI testing-eligible PrEP users who were tested for gonorrhea and chlamydia, gonorrhea prevalence was 6.7% for prepandemic and 5.7% for early pandemic ( P = 0.3096), and chlamydia prevalence was 7.0% for prepandemic and 5.8% for early pandemic ( P = 0.2158). CONCLUSIONS: Although the early COVID-19 pandemic resulted in lower numbers of PrEP users and PrEP initiators, individuals who remained continuous users of PrEP maintained extremely high rates of bacterial STI screening. With high STI prevalence among PrEP users, assessments of PrEP care management are continuously needed.

Knowledge of the epidemiology of sporadic acute gastroenteritis (AGE) in the United States is limited. During September 2016-September 2017, we surveyed Kaiser Permanente Northwest members in Oregon and Washington, USA, to collect data on the 30-day prevalence of dually defined AGE and diarrhea disease and related health-seeking behavior; from a subset of participants, we obtained a stool specimen. Using the iterative proportional fitting algorithm with raked weights, we generated AGE prevalence and annualized rate estimates. We detected norovirus, rotavirus, astrovirus, and sapovirus from submitted stool specimens through real-time quantitative reverse transcription PCR (qRT-PCR). We estimated a 30-day prevalence of 10.4% for AGE and 7.6% for diarrhea only; annual rates were 1.27 cases/person/year for AGE and 0.92 cases/person/year for diarrhea only. Of those with AGE, 19% sought medical care. Almost one quarter (22.4%) of stool specimens from those reporting AGE tested positive for ≥1 viral pathogen, compared with 8.2% from those without AGE.

BACKGROUND: Initial and follow-up sexually transmitted infection (STI) and HIV testing is recommended when taking HIV preexposure prophylaxis (PrEP). We assessed STI services before and after PrEP initiation among persons aged ≥18 years. METHODS: We conducted this retrospective cohort study at an US integrated healthcare delivery system. We measured HIV/STI testing rates, STI prevalence and treatment at 3 time points: (1) at PrEP initiation, (2) at 120 days, and (3) at 210 days. RESULTS: Of 685 PrEP initiators, 67.2% continued PrEP use at 120 days and 49.5% at 210 days. Of PrEP users, HIV and STI testing were > 85% and > 80%, respectively, at all 3 time points. Prevalence for any chlamydia, rectal chlamydia, and any gonorrhea, rectal gonorrhea, or pharyngeal gonorrhea was always high at the 120 days and 210 days (e.g, 6.9%, 10.5%, 6.7%, 5.0%, and 5.2%, respectively, at the 120-days for continuous PrEP users). Over 90% of all individuals who tested positive for chlamydia and/or gonorrhea received antibiotic pharmacy fills within seven days at 120 days and 210 days. Monthly PrEP-related pharmacy cost was about $2259-$2659. The proportion of the total medical cost that was PrEP-related pharmacy was about 82% for PrEP continuous users. CONCLUSIONS: Although HIV/STI testing rates were high, they can still be improved during HIV PrEP management. High STI prevalence after PrEP initiation in this study suggests that patients taking PrEP are at risk of acquiring an STI. Interventions to improve STI services during PrEP management are continuously needed.

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.

We compared rates of emergency department (ED) visits and hospitalizations between HCV patients who achieved sustained virological response (SVR) after direct-acting antiviral (DAA) therapy (cases) to matched controls. Among 3049 pairs, cases demonstrated lower rates of liver-related ED visits (P=.01) than controls; all-cause and liver-related hospitalization rates and hospitalized days were also lower in cases (P<.0001).

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 5,773 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 non-hepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Using electronic health records, we found that hepatitis C reporting on death certificates of 2,901 HCV-infected decedents from four U.S. 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 U.S. HCV mortality burden.

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014 - June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into one episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged <5 years (20.4 episodes per 1000 PY), followed by adults aged 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY, astrovirus: 1.3 per 1000 PY, rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are an important contributor to MAAGE, especially among children <5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014 - June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into one episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged <5 years (20.4 episodes per 1000 PY), followed by adults aged ≥65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY, astrovirus: 1.3 per 1000 PY, rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are an important contributor to MAAGE, especially among children <5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

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(s): 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.

BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.

GOALS: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). BACKGROUND: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. STUDY: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. RESULTS: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in >/=12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. CONCLUSIONS: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited.

PURPOSE: Little is known about health-related quality of life (HRQoL) in patients with chronic hepatitis B virus (CHB) infection in the United States. Our goal is to understand factors associated with HRQoL in this population. METHODS: We conducted a survey to assess HRQoL and behavioral risks among patients with CHB infection from four large U.S. health care systems. Primary outcomes were generated from the SF-8 scale to assess HRQoL, as measured by the mental component scores (MCS) and physical component scores (PCS). The survey also measured socio-demographic information, hepatitis-related behavioral risk factors, treatment exposure/history, stress, and social support. We supplemented survey data with electronic health records data on patient income, insurance, disease severity, and comorbidities. Multivariate analysis was used to estimate and compare adjusted least square means of MCS and PCS, and examine which risk factors were associated with lower MCS and PCS. RESULTS: Nine hundred sixty-nine patients (44.6%) responded to the survey. Current life stressors and unemployment were associated with both lower MCS and PCS results in multivariate analyses. Lower MCS was also associated with White race and low social support, while lower PCS was also associated with Medicaid insurance. CONCLUSIONS: Stressful life events and unemployment were related to mental and physical health status of CHB patients. Those who have social support have better mental health; White and Medicaid patients are more likely to have poorer mental and physical health, respectively. Management of CHB patients should include stress management, social support, and financial or employment assistance.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is typically asymptomatic until severe liver disease occurs and even then can remain undiagnosed for some time; thus, screening and treatment of asymptomatic persons are needed to prevent poor outcomes. In a previous analysis of data from between 2006 and 2011, we found that 17% of newly diagnosed HCV infections in 4 large health systems were among persons with cirrhosis and/or end-stage liver disease, termed "late diagnosis." We sought to determine the proportion with late diagnosis during 2014-2016, after release of CDC baby boomer (1945-1965 birth cohort) testing guidelines in 2012. STUDY DESIGN: The cohort was based on analysis of electronic health records and administrative data of about 2.7 million patients visiting the same healthcare systems during 2014-2016. METHODS: Among persons with newly diagnosed chronic HCV infection during 2014-2016, we analyzed data collected up to January 1, 2017. RESULTS: Among 2695 patients with newly diagnosed HCV infection, 576 (21.4%) had late diagnosis. Most were born between 1945 and 1965 (n = 1613 [59.9%]), and among these, 27.6% had late diagnosis. Patients with versus without late diagnosis had equally lengthy prediagnosis observation in the health systems (mean and median, 9.1 and 9.1 vs 8.3 and 7.8 years, respectively) but were more likely to have a postdiagnosis hospitalization (32.5% vs 12.5%; P <.001) with greater number of hospital days (358.8 vs 78.5 per 100 person-years; P <.001). CONCLUSIONS: More than one-fifth of patients with newly diagnosed HCV infection during 2014-2016-and more than a quarter of those born between 1945 and 1965-had late diagnosis despite many years of in-system care, an increase of 5 percentage points since 2006-2011, after the interim initiation of age-based screening recommendations. Our data highlight missed opportunities for diagnosis and therapeutic intervention before the onset of severe liver disease, which is associated with high cost and diminished outcomes.

Background: Trends in the epidemiology of chronic hepatitis B (CHB) among routine clinical care patients in the United States are not well documented. We used data from the Chronic Hepatitis Cohort Study to investigate changes in prevalence and newly recorded cases of CHB from 2006 to 2015. Methods: Annual percentage changes (APCs) were estimated using join point Poisson regression. Analyses were adjusted by study site; when an interaction with the trend was observed, APCs were estimated by subgroups. Differences in rates based on race, age, and sex were calculated with rate ratios. Results: We identified 5492 patients with CHB within select health systems with total populations that ranged from 1.9 to 2.4 million persons. From 2006 to 2014, the prevalence of diagnosed CHB increased from 181.3 to 253.0 per 100 000 persons in the health system population; from 2014 to 2015, it declined to 237.0 per 100 000 persons. APC was +3.7%/y through 131 December 2014 (P < .001) and -15.0%/y (P < .001) thereafter. The rate of newly reported cases of CHB did not change significantly across the study period (APC, -1.1%/y; P = .07). The rates of newly reported cases were 20.5 times higher among patients in the Asian American/American Indian/Pacific Islander (ASINPI) category, compared with white patients, and 2.8 times higher among African American patients. The ratio of male to female patients was roughly 3:2. Conclusions: The prevalence of diagnosed CHB in this US patient population increased from 2006 to 2014, after which it decreased significantly. Rates declined most rapidly among patients </=40 or 61-70 years old, as well as among ASINPI patients. The rate of newly reported cases remained steady over the study period.

The role of ribavirin (RBV) in the era of direct-acting antivirals (DAA) is not clear, and DAA studies have been largely genotype- and regimen-specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. Multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir +SOF; grazoprevir +elbasvir; paritaprevir/ ritonavir +ombitasvir; simeprevir +SOF; and SOF +ledipasvir; SOF +velpatasvir +/-voxilaprevir; and glecaprevir+pibrentasvir-all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment-selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12+/-4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naive, interferon treatment failure [TF], or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one month increment of treatment duration increased odds of SVR by 99% (aOR=1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR=5.05), previous DAA treatment failure (aOR=5.43), and GT3 (aOR=13.28). Among RBV-free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis. This article is protected by copyright. All rights reserved.

BACKGROUND: The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied. AIM: We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). METHODS: We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event. RESULTS: Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate. CONCLUSION: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.

BACKGROUND: Sustained virological response (SVR) to treatment for chronic hepatitis C (HCV) may improve short-term glucose control among patients with type 2 diabetes (T2D), but the long-term impact remains largely unknown. We used data from the Chronic Hepatitis Cohort Study to investigate the impact of SVR on long-term trends in HbA1c in patients with T2D. METHODS: "Index date" was defined as the date of treatment initiation (treated patients) or HCV diagnosis (untreated patients). To address treatment selection bias, we used a propensity score approach. We used a piecewise, linear-spline, mixed-effects model to evaluate changes in HbA1c over a five-year period. RESULTS: Our sample included 384 HCV patients with T2D (192 untreated, 192 treated, with SVR or treatment failure [TF]). After adjusting for BMI, HbA1c was stable among untreated and TF patients. In SVR patients, Hb1Ac trajectories evolved in three phases: 1) index through 6 months post-index, average HbA1c decreased significantly from 7.7-5.4% per 90 days (p<0.001); 2) 6-30 months post-index, HbA1c rebounded at a rate of 1.5% every 90 days (p=0.003); and 3) from 30 months onward, HbA1c stabilized at an average level of 7.9 (p-value =0.34). Results from an analysis restricted to patients receiving direct-acting antivirals were consistent with the main findings. CONCLUSION: Successful HCV treatment among patients with T2D significantly reduces HbA1 shortly after treatment, but these decreases are not sustained long-term. Less than three years after SVR, HbA1c rebounds to levels similar to untreated/TF patients, and higher than recommended for type 2 diabetic maintenance. This article is protected by copyright. All rights reserved.

BACKGROUND: This study presents a novel methodology for estimating all-age, population-based incidence rates of norovirus and other pathogens that contribute to acute gastroenteritis in the United States using an integrated healthcare delivery system as a surveillance platform. METHODS: All cases of medically attended acute gastroenteritis within the delivery system were identified from April 1, 2014 through September 30, 2016. A sample of these eligible patients were selected to participate in two phone-based surveys and to self-collect a stool sample for laboratory testing. To ascertain household transmission patterns, information on household members with acute gastroenteritis was gathered from participants, and symptomatic household members were contacted to participate in a survey and provide stool sample as well. RESULTS: 54% of individuals who met enrollment criteria agreed to participate, and 76% of those individuals returned a stool sample. Among household members, 85% of eligible individuals agreed to participate, and 68% of those returned a stool sample. Participant demographics were similar to those of the eligible population, although minority racial/ethnic groups were somewhat underrepresented in the final sample. CONCLUSIONS: This study demonstrates the feasibility of conducting acute infectious disease research within an integrated health care delivery system. The surveillance, sampling, recruitment, and data collection methods described here are broadly applicable to conduct baseline and epidemiological assessments, as well as for other research requiring representative samples of stool specimens.

Chronic Hepatitis Cohort Study (CHeCS) publications using data from "real-world" patients with hepatitis C virus (HCV) have described demographic disparities in access to care; rates of advanced liver disease, morbidity, and mortality (2.5%-3.5% per year during 2006-10, although only 19% of all CHeCS decedents, and just 30% of those with deaths attributed to liver disease, had HCV listed on death certificate); substantial comorbidities, such as diabetes, advanced liver fibrosis (29% prevalence), renal disease, and depression, and partial reversal of all these with successful antiviral therapy; patient risk behaviors; and use of noninvasive markers to assess liver disease.

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases ("gold standard" definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) >/=2 ICD-9 codes separated by >/= 6 months and (2) >/=1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (>/= 2 ICD-9 codes separated by >/= 6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (>/= 1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data.

Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts risk of subsequent type 2 diabetes mellitus. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated incidence of type 2 diabetes mellitus from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virological response [SVR] or treatment failure) and baseline risk factors on development of type 2 diabetes mellitus, considering any possible risk factor-by-SVR interactions and death as a competing risk. Among 5,127 patients with an average follow-up of 3.7 years, type 2 diabetes mellitus incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR]= 0.79; 95%CI 0.65-0.96). Risk of type 2 diabetes mellitus was higher among African American and Asian American patients than white patients (aHR=1.82 and 1.75, respectively; p<0.05), and among Hispanic patients than non-Hispanics (aHR=1.86). Patients with BMI >/=30 and 25-30 (aHR=3.62 and 1.72, respectively; p<0.05) demonstrated higher risk than those with BMI <25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR=1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for development of type 2 diabetes mellitus than patients with treatment failure. This article is protected by copyright. All rights reserved.