Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Risk Factors for Not Completing a 2-Dose Primary Series of Messenger RNA COVID-19 Vaccination in a Large Health Care System in Southern California: Retrospective Cohort Study.

BACKGROUND: COVID-19 vaccination is crucial in combating the COVID-19 pandemic. Messenger RNA COVID-19 vaccines were initially authorized as a 2-dose primary series and have been widely used in the United States; completing the 2-dose primary series offers protection against infection, severe illness, and death. Understanding the risk factors for not completing the 2-dose primary series is critical to evaluate COVID-19 vaccination programs and promote completion of the 2-dose primary series. OBJECTIVE: This study examined potential risk factors for not completing a 2-dose primary series of mRNA COVID-19 vaccination. METHODS: We conducted a retrospective cohort study among members aged ≥18 years from a large integrated health care system, Kaiser Permanente Southern California, from December 14, 2020, to June 30, 2022. Noncompletion of the 2-dose primary series was defined as not completing the second dose within 6 months after receipt of the first dose. Crude noncompletion rates were estimated overall and by demographic characteristics, health care use patterns, comorbidity, and community-level socioeconomic factors. A Poisson regression model was fit to examine associations of individual-level and community-level risk factors with noncompletion of the 2-dose primary series. RESULTS: Among 2.5 million recipients of ≥1 dose of mRNA COVID-19 vaccines, 3.3% (n=81,202) did not complete the second dose within 6 months. Members aged 25-44 years, 65-74 years, and ≥75 years were less likely to not complete the 2-dose primary series than those aged 18-24 years, while members aged 45-64 years were more likely to not complete the 2-dose primary series (adjusted risk ratio [aRR] 1.13, 95% CI 1.10-1.15). Male sex was associated with a higher risk of noncompletion (aRR 1.17, 95% CI 1.15-1.19). Hispanic and non-Hispanic Black race/ethnicity were associated with a lower risk of noncompletion (range aRR 0.78-0.91). Having Medicaid and prior influenza vaccination were associated with a higher risk of noncompletion. Having SARS-CoV-2 infection, experiencing an adverse event, or having an inpatient and emergency department visit during the minimum recommended dose intervals were associated with a higher risk of not completing the 2-dose primary series (aRR 1.98, 95% CI 1.85-2.12; 1.99, 95% CI 1.43-2.76; and 1.85, 95% CI 1.77-1.93, respectively). Those who received the first dose after June 30, 2021, were more likely to not complete the 2-dose primary series within 6 months of receipt of the first dose. CONCLUSIONS: Despite limitations such as being a single-site study and the inability to consider social factors such as employment and vaccine attitudes, our study identified several risk factors for not completing a 2-dose primary series of mRNA vaccination, including being male; having Medicaid coverage; and experiencing SARS-CoV-2 infection, adverse events, or inpatient and emergency department visits during the minimum recommended dose intervals. These findings can inform future efforts in developing effective strategies to enhance vaccination coverage and improve the completion rate of necessary doses.

Multidrug Resistance of Escherichia coli From Outpatient Uncomplicated Urinary Tract Infections in a Large United States Integrated Healthcare Organization.

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

Latent Tuberculosis Infection Treatment Practices in Two Large Integrated Health Systems in California, 2009-2018.

Background: Treatment of latent tuberculosis infection (LTBI) is highly effective at preventing active tuberculosis (TB) disease. Understanding LTBI treatment practices in US health system settings is critical to identify opportunities to improve treatment prescription, initiation, and completion, and thus to prevent TB disease. Methods: We assessed LTBI treatment practices among a cohort of adults after their first positive LTBI test (tuberculin skin test [TST] or interferon gamma release assay [IGRA]) between 2009 and 2018 at 2 large integrated health systems in California. We described the prescription, initiation, and completion of LTBI treatment (isoniazid [INH], rifampin, and rifamycin-INH short-course combinations) by demographic and clinical characteristics. We used multivariable robust Poisson regression to examine factors that were independently associated with treatment prescription and completion. Results: Among 79 302 individuals with a positive LTBI test, 33.0% were prescribed LTBI treatment, 28.3% initiated treatment, and 18.5% completed treatment. Most individuals were prescribed INH (82.0%), but treatment completion was higher among those prescribed rifamycin-INH short-course combinations (69.6% for INH + rifapentine and 70.3% for INH + rifampin) compared with those prescribed INH (56.3%) or rifampin (56.6%). In adjusted analyses, treatment prescription and completion were associated with older age, female sex, more comorbidities, immunosuppression, not being born in a high-TB incidence country, and testing positive with IGRA vs TST. Conclusions: LTBI treatment is underutilized, requiring tailored interventions to support treatment prescription and completion for patients with LTBI.

Patient-Reported Barriers to Treatment Initiation and Completion for Latent Tuberculosis Infection Among Patients Within a Large Integrated Health Care System in Southern California.

OBJECTIVE: More than 80% of active tuberculosis in the United States is due to reactivation of latent tuberculosis infection (LTBI), which can be prevented via screening and treatment. Treatment initiation and completion rates are low for patients with LTBI in the United States, and the barriers to successful treatment are poorly understood. DESIGN: We conducted semistructured qualitative interviews with 38 patients who were prescribed LTBI treatment (9 months isoniazid, 6 months rifampin, or 3 months rifamycin-isoniazid short-course combinations). We used purposeful sampling employing a maximum variation approach to obtain diverse perspectives of patients who did not initiate treatment, who did not complete treatment, and who completed treatment (n = 14, n = 16, and n = 8, respectively). Patients were asked about LTBI knowledge, experience regarding treatment, interactions with providers, and barriers they faced. Using a team coding model (2 coders/analysts), we developed deductively derived (a priori) codes based on our central research questions and inductively derived codes that emerged directly from the data. Analysis of our coding categories and relationships generated a hierarchy of key themes and subthemes. SETTING: Kaiser Permanente Southern California. PARTICIPANTS: Individuals 18 years or older who received a diagnosis of LTBI and prescribed treatment. MAIN OUTCOME MEASURES: LTBI knowledge, attitudes toward LTBI, attitudes toward LTBI treatment, attitudes toward providers, and explanation of barriers. RESULTS: Most patients reported having limited knowledge of LTBI. In addition to the duration of treatment, barriers to initiation and completion included perceived lack of support, uncomfortable side effects, and pervasive minimization of the positive impact of treatment on their health. Many patients felt there was little incentive to overcome barriers. CONCLUSIONS: Overall, patient experience with LTBI treatment initiation and completion could be improved with patient-centered treatment and more frequent follow-ups.

Understanding Barriers and Facilitators of Pre-exposure Prophylaxis (PrEP) Among Transgender and Gender Diverse Adults in an Integrated Health Care System.

Transgender and gender diverse individuals face health disparities such as higher HIV prevalence, but limited studies have found low PrEP uptake among these populations. To understand both patient and provider perspectives regarding PrEP care for transgender and gender diverse individuals, we conducted a mixed-methods study at Kaiser Permanente Southern California from September 2020 to October 2021. Transgender and gender diverse adults (N = 396) participated in a web-based survey, and qualitative interviews were subsequently conducted with a subset of survey respondents (N = 32) and healthcare providers (N = 8). Among survey respondents, > 75% were familiar with PrEP, and > 40% reported at least one HIV risk factor, but < 5% had taken PrEP. Interview themes included increasing providers' inclusivity in primary care for transgender and gender diverse patients, and reducing logistical barriers and costs associated with PrEP-related visits. To improve PrEP uptake among transgender and gender diverse individuals, barriers across patient, provider, and health system levels must be addressed.

Sexually Transmitted Infections Among Men and Transgender Women Using HIV Pre-exposure Prophylaxis in a Large Integrated Health System-A Cohort Study.

BACKGROUND: Sexually transmitted infections (STIs) are common in people using pre-exposure prophylaxis (PrEP). We examined risk and factors associated with STIs in a cohort of PrEP users in an integrated health system in the United States. SETTING: The Kaiser Permanente Southern California is a large integrated health system that provides comprehensive medical services to approximately 4.7 million demographically diverse members. METHODS: We identified men and transgender women initiating PrEP between January 1, 2014, and June 1, 2018, and followed through December 31, 2018. Demographic and clinical factors potentially associated with the risk of bacterial STIs during PrEP use were evaluated using Poisson regression models. RESULTS: Among 5042 individuals tested for STIs with 7198 person-years of follow-up, 1709 (33.9%) had at least one new STI. The estimated incidence of STIs was 48.3 per 100 person-years, and the most common STI was rectal chlamydia. Most repeat STIs (61.4%) occurred <180 days apart. In a multivariable analysis, an history of STIs in the prior 6 months through 7 days after the PrEP initiation was the most prominent risk factor of STIs during PrEP use (adjusted risk ratio: 1.78, 95% confidence intervals: 1.65 to 1.93). Other risk factors included younger age (<35 years), being Hispanic, and having a history of alcohol use disorder or drug use disorder. CONCLUSIONS: Quarterly STI testing and targeted intervention to mitigate STI risk are warranted for young and racial minority PrEP users, particularly for those with prior history of STIs and substance use disorders.

"Still on the Fence": A Mixed Methods Investigation of COVID-19 Vaccine Confidence Among Health Care Providers.

BACKGROUND: There is evidence of disparities in COVID-19 vaccine acceptance among health care providers. The purpose of this study was to examine confidence receiving and recommending COVID-19 vaccines by health care provider type and race/ethnicity. METHODS: This mixed methods study involved a cross-sectional survey and qualitative, semi-structured interviews from March to May 2021 among a sample of physicians, advanced practice providers, nurses, and pharmacists. These workers were recruited through voluntary response sampling from an integrated health system in Southern California. The primary dependent variables were (a) confidence in vaccine safety, (b) confidence in vaccine effectiveness, and (c) intent to recommend the vaccine to others. The primary independent variables were health care provider type and race/ethnicity. FINDINGS: A total of 2,948 providers completed the survey. Nurses relative to physicians were 15% less likely to perceive the COVID-19 vaccine to be safe (risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.83-0.87); 27% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.73; 95% CI = 0.69-0.76); and 11% less likely to recommend the vaccine to others (RR = 0.89; 95% CI = 0.87-0.91). Hispanic/Latinx providers were 10% less likely to perceive the vaccine to prevent COVID-19 (RR = 0.90; 95% CI = 0.83-0.98) relative to White providers. Qualitative themes included: No need for vaccine; distrusting vaccine research and roll-out; caretaking barriers; uncertainty and potential to change one's mind; framing vaccine decisions around personal beliefs. CONCLUSIONS & APPLICATION TO PRACTICE: Health care workplaces should consider interventions to increase COVID-19 vaccination among their workers, including education and mandatory vaccination policies.

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction.

Importance: The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study. Objective: To compare the rate of acute MI between recipients of HepB-CpG vaccine and HepB-alum vaccine. Design, Setting, and Participants: This prospective cohort noninferiority study was conducted at Kaiser Permanente Southern California (KPSC), an integrated health care system with 15 medical centers and approximately 4.7 million members. The study included 69 625 adults not undergoing dialysis who received at least 1 dose of a hepatitis B vaccine in either family medicine or internal medicine departments at KPSC from August 7, 2018, to October 31, 2019 (November 30, 2020, final follow-up). Exposures: Receipt of HepB-CpG vaccine vs HepB-alum vaccine. The first dose during the study period was the index dose. Main Outcomes and Measures: Individuals were followed up for 13 months after the index dose for occurrence of type 1 acute MI. Potential events were identified using diagnosis codes and adjudicated by cardiologists. The adjusted hazard ratio (HR) of acute MI was estimated comparing recipients of HepB-CpG vaccine with recipients of HepB-alum vaccine, with inverse probability of treatment weighting (IPTW) to adjust for demographic and clinical characteristics. The upper limit of the 1-sided 97.5% CI was compared with a noninferiority margin of 2. Results: Of the 31 183 recipients of HepB-CpG vaccine (median age, 49 years; IQR, 38-56 years), 51.2% (n = 15 965) were men, and 52.7% (n = 16 423) were Hispanic. Of the 38 442 recipients of HepB-alum (median age, 49 years; IQR, 39-56 years), 50.8% (19 533) were men, and 47.1% (n = 18 125) were Hispanic. Characteristics were well-balanced between vaccine groups after IPTW. Fifty-two type 1 acute MI events were confirmed among recipients of HepB-CpG vaccine for a rate of 1.67 per 1000-person-years, and 71 type 1 acute MI events were confirmed among recipients of HepB-alum vaccine for a rate of 1.86 per 1000 person-years (absolute rate difference, -0.19 [95% CI, -0.82 to 0.44]; adjusted HR, 0.92 [1-sided 97.5% CI, ∞ to 1.32], which was below the noninferiority margin; P < .001 for noninferiority). Conclusions and Relevance: In this cohort study, receipt of HepB-CpG vaccine compared with HepB-alum vaccine did not meet the statistical criterion for increased risk of acute myocardial infarction.

Influenza vaccination and mortality among adults with heart failure in an integrated healthcare delivery system, 2009-2018.

BACKGROUND: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. OBJECTIVE: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. EXPOSURE: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). MAIN OUTCOMES: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. RESULTS: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). CONCLUSIONS: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.

Parent intentions to vaccinate children with autism spectrum disorder against COVID-19.

PURPOSE: The purpose of this study was to investigate associations between parent vaccine confidence and intention to have their child with autism vaccinated against COVID-19. DESIGN AND METHODS: A cross-sectional, web-based survey was conducted from May to July 2021 with parents of children with autism spectrum disorder (N = 322) who were members of an integrated healthcare system in Southern California. RESULTS: Approximately 35% of parents intended to vaccinate their child against COVID-19. In adjusted models, positive vaccine beliefs-but not belief in vaccine harm, healthcare provider trust, or parent vaccination status-were associated with intention to vaccinate. CONCLUSIONS: Though parents usually trust recommendations from pediatric healthcare providers to make decisions about their child's health, these findings suggest that relying on trusted relationships alone may not be sufficient when discussing COVID-19 vaccines and that additional education to bolster vaccine confidence may be needed. PRACTICE IMPLICATIONS: Pediatric healthcare providers should reinforce the benefits of vaccines for parents who are undecided about COVID-19 vaccines for their children and provide education and evidence-based recommendations to parents who hold erroneous vaccine beliefs about risks, benefits, and current evidence, especially those related to autism.

Health Care Providers' Trusted Sources for Information About COVID-19 Vaccines: Mixed Methods Study.

BACKGROUND: Information and opinions shared by health care providers can affect patient vaccination decisions, but little is known about who health care providers themselves trust for information in the context of new COVID-19 vaccines. OBJECTIVE: The purpose of this study is to investigate which sources of information about COVID-19 vaccines are trusted by health care providers and how they communicate this information to patients. METHODS: This mixed methods study involved a one-time, web-based survey of health care providers and qualitative interviews with a subset of survey respondents. Health care providers (physicians, advanced practice providers, pharmacists, nurses) were recruited from an integrated health system in Southern California using voluntary response sampling, with follow-up interviews with providers who either accepted or declined a COVID-19 vaccine. The outcome was the type of information sources that respondents reported trusting for information about COVID-19 vaccines. Bivariate tests were used to compare trusted information sources by provider type; thematic analysis was used to explore perspectives about vaccine information and communicating with patients about vaccines. RESULTS: The survey was completed by 2948 providers, of whom 91% (n=2683) responded that they had received ≥1 dose of a COVID-19 vaccine. The most frequently trusted source of COVID-19 vaccine information was government agencies (n=2513, 84.2%); the least frequently trusted source was social media (n=691, 9.5%). More physicians trusted government agencies (n=1226, 93%) than nurses (n=927, 78%) or pharmacists (n=203, 78%; P<.001), and more physicians trusted their employer (n=1115, 84%) than advanced practice providers (n=95, 67%) and nurses (n=759, 64%; P=.002). Qualitative themes (n=32 participants) about trusted sources of COVID-19 vaccine information were identified: processing new COVID-19 information in a health care work context likened to a "war zone" during the pandemic and communicating information to patients. Some providers were hesitant to recommend vaccines to pregnant people and groups they perceived to be at low risk for COVID-19. CONCLUSIONS: Physicians have stronger trust in government sources and their employers for information about COVID-19 vaccines compared with nurses, pharmacists, and advanced practice providers. Strategies such as role modeling, tailored messaging, or talking points with standard language may help providers to communicate accurate COVID-19 vaccine information to patients, and these strategies may also be used with providers with lower levels of trust in reputable information sources.

Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study.

OBJECTIVES: To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. DESIGN: Test negative case-control study. SETTING: Kaiser Permanente Southern California (KPSC), an integrated healthcare system. PARTICIPANTS: Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. INTERVENTIONS: Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. MAIN OUTCOME MEASURES: Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1-odds ratio)×100%. RESULTS: The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. CONCLUSIONS: Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System - California, March-July 2021.

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

Brief Report: COVID-19 Testing, Characteristics, and Outcomes Among People Living With HIV in an Integrated Health System.

BACKGROUND: Understanding the attributes of COVID-19 clinical severity among people living with HIV (PLWH) compared with those in HIV-uninfected patients is critical for risk stratification and treatment strategies. METHODS: We conducted a retrospective study at Kaiser Permanente Southern California among PLWH aged 18 years or older. We compared the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization among PLWH and HIV-uninfected adults. A chart review was conducted for PLWH with COVID-19 to examine viral suppression of HIV and most recent CD4+ counts in the year before COVID-19 diagnosis, known exposures to COVID-19, and clinical presentation. RESULTS: Between March 1, 2020, and May 31, 2020, the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization was 551.2, 57.0, and 9.3 per 10,000 PLWH, respectively, compared with 268.4, 34.6, and 5.3 per 10,000 HIV-uninfected individuals, respectively. Among those with COVID-19, the distribution of race/ethnicity, smoking status, and comorbidities was similar in PLWH and HIV-uninfected patients; however, PLWH were mostly men, younger, and less obese than HIV-uninfected individuals. Health care utilization regarding emergency care and hospitalizations in the year before COVID-19-related hospitalization was similar between the groups. Overall, HIV was virologically suppressed in >95% of PLWH with COVID-19, and HIV viral load and CD4+ status did not differ between hospitalized and nonhospitalized patients. CONCLUSIONS: In this population of patients with well-controlled HIV infection, the incidence of testing, diagnosis, and hospitalization for COVID-19 was higher in PLWH than that in HIV-uninfected patients.

Challenges in Phase 4 post-licensure safety studies using real world data in the United States: Hepatitis B vaccine example.

Post-licensure vaccine safety studies are essential to identify adverse events that may not have been detected in pre-licensure clinical trials and to address questions that arose during the pre-licensure phase. These studies are increasingly conducted using real-world data collected as part of routine health care delivery. However, design of post-licensure vaccine safety studies involves many pragmatic and scientific decisions, which must be made while balancing diverse stakeholder opinions. Challenges include selecting exposure and comparison groups, deciding on the most appropriate outcome, determining sample size and length of follow-up time, and other analytic considerations. As an example of this process and to inform other post-licensure vaccine safety studies in real-world settings, we discuss our experience with design of an FDA-required Phase 4 post-licensure safety study of a hepatitis B vaccine in a large integrated health care organization in the United States.

Referral Linkage to Preexposure Prophylaxis Care and Persistence on Preexposure Prophylaxis in an Integrated Health Care System.

BACKGROUND: Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS: We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS: Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged <25 years (vs ≥25 years), female subjects (vs males), and individuals with high-deductible insurance (vs no high deductible) were less likely to be linked to care. Individuals aged <25 years and Hispanics (vs non-Hispanic whites) were less likely to be persistent. Those with alcohol use disorder were more likely to be linked to PrEP care but less likely to be persistent. New HIV diagnoses occurred in 38 individuals, and only 1 had PrEP in possession at diagnosis. CONCLUSIONS: We observed PrEP care gaps and disparities among individuals referred for PrEP. Patient-centered interventions are needed in primary care to address barriers to successful PrEP linkage and persistence.

Association of Number of Doses With Hepatitis B Vaccine Series Completion in US Adults.

Importance: Receipt of hepatitis B virus vaccine is important to prevent infection. However, adherence to the hepatitis B vaccine series among adults at risk of infection has been low. Objective: To assess whether recipients of a 2-dose hepatitis B vaccine with cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) are more likely to complete their series compared with recipients of a 3-dose vaccine with alum adjuvant (comparator vaccine; Engerix-B [HepB-alum]). Design, Setting, and Participants: This nested cohort study was conducted from August 7 to December 31, 2018, at Kaiser Permanente Southern California, an integrated health care system with a diverse population of approximately 4.6 million members. Adults not receiving dialysis who received a first dose of a hepatitis B vaccine series in family practice or internal medicine departments of 15 Kaiser Permanente Southern California medical centers were followed up through electronic health records for up to 1 year after receipt of the first dose. Data were analyzed from March 16 to September 23, 2020. Exposures: Receipt of a first dose of the HepB-CpG vaccine (2-dose vaccine) vs receipt of a first dose of the HepB-alum vaccine (3-dose vaccine). Main Outcomes and Measures: Series completion within the recommended vaccine schedule plus 3 months (primary outcome) and series completion within 1 year after receipt of the first dose (secondary outcome). Results: Of 4727 individuals who initiated the HepB-CpG vaccine series and 6161 individuals who initiated the HepB-alum vaccine series included in the study, 2876 (60.8%) and 3789 (61.5%), respectively, were ages 40 to 59 years, 2415 (51.1%) and 3113 (50.5%) were male, and 2364 (50.0%) and 2881 (46.8%) were Hispanic. The vaccine series was completed within the recommended schedule plus 3 months for 2111 (44.7%) individuals who initiated the HepB-CpG vaccine series and 1607 (26.1%) individuals who initiated the HepB-alum vaccine series, and within 1 year for 2858 (60.5%) and 1989 (32.3%) individuals, respectively. The individuals who initiated the HepB-CpG vaccine series were significantly more likely to complete the series (adjusted relative risk, 1.77; 95% CI, 1.68-1.87). Results were consistent across clinical and demographic strata. Conclusions and Relevance: In this study, use of the HepB-CpG vaccine was associated with hepatitis B vaccine series completion, but tailored strategies to increase completion of hepatitis B vaccine series are warranted.

Universal SARS-Cov-2 Screening in Women Admitted for Delivery in a Large Managed Care Organization.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has created a need for data regarding the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women. After implementing universal screening for COVID-19 in women admitted for delivery, we sought to describe the characteristics of COVID-19 in this large cohort of women. STUDY DESIGN: An observational study of women admitted to labor and delivery units in Kaiser Permanente Southern California (KPSC) hospitals between April 6 and May 11, 2020 who were universally offered testing for SARS-CoV-2 infection (n = 3,963). Hospital inpatient and outpatient physician encounter, and laboratory records were used to ascertain universal testing levels, test results, and medical and obstetrical histories. The prevalence of SARS-CoV-2 infection was estimated from the number of women who tested positive during labor per 100 women delivered. RESULTS: Of women delivered during the study period, 3,923 (99.0%) underwent SARS-CoV-2 testing. A total of 17 (0.43%; 95% confidence interval: 0.23-0.63%) women tested positive, and none of them were symptomatic on admission. There was no difference in terms of characteristics between SARS-CoV-2 positive and negative tested women. One woman developed a headache attributed to COVID-19 3 days postpartum. No neonates had a positive test at 24 hours of life. CONCLUSION: The findings suggest that in pregnant women admitted for delivery between April 6 and May 11, 2020 in this large integrated health care system in Southern California, prevalence of SARS-CoV-2 test positive was very low and all patients were asymptomatic on admission. KEY POINTS: · The prevalence of SARS-CoV-2 infection in a large diverse cohort of term pregnant women was 0.43%.. · 99% of women accepted SARS-CoV-2 screening on admission to labor and delivery.. · All women with positive test results were asymptomatic at the time of testing..