Ana Florea

Objectives: Little is known about the impact of Clostridioides difficile infection (CDI) on health-related quality of life (HRQoL) among adults in the community. We examined the impact of CDI on HRQoL among adults with CDI in the outpatient setting and compared it to HRQoL among patients without CDI.Methods: We conducted a prospective study among adult Kaiser Permanente members ≥50 years with CDI in the outpatient setting (cases) and members ≥45 years who had an outpatient encounter without diarrhea or C. difficile (controls). Cases and controls were not hospitalized within 7 days. Cases and controls completed the EQ-5D-5L at baseline and after 60 days.Results: Our analyses included 213 adults with CDI and 426 adults without CDI. Adults with and without CDI reported similar perceived health status [median visual analogue scale (VAS) of 80.0 and 81.0, (p=0.08)] and utility index scores [median of 0.9 for both; (p=0.16)] before illness. On their worst day, adults with CDI reported lower perceived health status and utility index scores, compared to pre-infection (p<0.0001). Decrements in median VAS and utility indices among adults with CDI from pre-infection to worst day were significantly greater than decrements among adults without CDI (p<0.0001 for both). At 60 days, adults with and without CDI had VAS and utility index scores similar to pre-illness levels.Conclusions: Adults with CDI experienced significant reductions in HRQoL on the worst day of illness that were greater than that experienced by those without CDI. HRQoL among adults with CDI at 60 days was similar to pre-infection levels.

Context: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected. Objective: Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring. Design: Retrospective cohort study. Setting and Participants: We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review. Main Outcome Measures: Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without. Results: Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging. Conclusions: Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8–52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7–60.7) in 2016 to 45.7 (95% CI, 43.7–47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were “community-associated” (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%–75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%–58.8%) and 82.7% (63.7%–91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza viruses can be transmitted by infected persons who are pre-symptomatic or symptomatic. To assess impact of the COVID-19 pandemic on work attendance during illness, we analyzed prospectively collected data from persons with acute respiratory illness (ARI) enrolled in a multi-state study during 2018–2022. Persons with prior experience working from home were significantly less likely than those without this experience to work onsite on the day before illness and during the first 3 days of illness; the effect was more pronounced for the COVID-19 pandemic period than the pre-pandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other ARIs. Among persons for whom positive COVID-19 test results were available by the second or third day of illness, few worked onsite. Work-from-home policies may reduce the likelihood of workplace exposures to respiratory viruses. Article’s summary line Work-from-home policies may reduce the likelihood of workplace exposures to SARS-CoV-2 and influenza viruses.

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

Background: Overuse of antibiotics contributes to antimicrobial resistance (AMR) and is a growing threat to human health worldwide. Previous work suggests a link between antimicrobial use in poultry and human AMR extraintestinal pathogenic Escherichia coli (E coli) urinary tract infections (UTIs). However, few US-based studies exist, and none have comprehensively assessed both foodborne and environmental pathways using advanced molecular and spatial epidemiologic methods in a quasi-experimental design. Recently, California enacted Senate Bill 27 (SB27), which changed previous policy to require a veterinarian’s prescription for the use of antibiotic drugs, and which banned antibiotic use for disease prevention in livestock. This provided an opportunity to evaluate whether SB27 will result in a reduction in antimicrobial-resistant infections in humans. Objective: We describe in detail the methods implemented to achieve the overarching objective of this study to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTIs. Methods: A summary of the overall approach and the partnerships between Columbia University, George Washington University (GWU), Johns Hopkins Bloomberg School of Public Health, Kaiser Permanente Southern California (KPSC) Research and Evaluation, the Natural Resources Defense Council, Sanger Institute at Stanford University, Sutter Health Center for Health Systems Research, the University of Cambridge, and the University of Oxford is presented. The collection, quality control testing, and shipment of retail meat and clinical samples are described. Retail meat (chicken, beef, turkey, and pork) was purchased from stores throughout Southern California from 2017 to 2021. After processing at KPSC, it was shipped to GWU for testing. From 2016 to 2021, after clinical specimens were processed for routine clinical purposes and immediately before discarding, those with isolated colonies of E coli, Campylobacter, and Salmonella from KPSC members were collected and processed to be shipped for testing at GWU. Detailed methods of the isolation and testing as well as the whole-genome sequencing of the meat and clinical samples at GWU are described. KPSC electronic health record data were used to track UTI cases and AMR patterns among the cultured specimens. Similarly, Sutter Health electronic health record data were used to track UTI cases in its Northern California patient population. Results: From 2017 to 2021, overall, 12,616 retail meat samples were purchased from 472 unique stores across Southern California. In addition, 31,643 positive clinical cultures were collected from KPSC members during the same study period. Conclusions: Here, we presented data collection methods for the study, which was conducted to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTI. To date, it is one of the largest studies of its kind to be conducted. The data collected during this study will be used as the foundation for future analyses specific to the various objectives of this large body of work. Trial Registration: