Natural Language Processing Versus Diagnosis Code-Based Methods for Postherpetic Neuralgia Identification: Algorithm Development and Validation.

Background: Diagnosis codes and prescription data are used in algorithms to identify postherpetic neuralgia (PHN), a debilitating complication of herpes zoster (HZ). Because of the questionable accuracy of codes and prescription data, manual chart review is sometimes used to identify PHN in electronic health records (EHRs), which can be costly and time-consuming. Objective: This study aims to develop and validate a natural language processing (NLP) algorithm for automatically identifying PHN from unstructured EHR data and to compare its performance with that of code-based methods. Methods: This retrospective study used EHR data from Kaiser Permanente Southern California, a large integrated health care system that serves over 4.8 million members. The source population included members aged ≥50 years who received an incident HZ diagnosis and accompanying antiviral prescription between 2018 and 2020 and had ≥1 encounter within 90-180 days of the incident HZ diagnosis. The study team manually reviewed the EHR and identified PHN cases. For NLP development and validation, 500 and 800 random samples from the source population were selected, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F-score, and Matthews correlation coefficient (MCC) of NLP and the code-based methods were evaluated using chart-reviewed results as the reference standard. Results: The NLP algorithm identified PHN cases with a 90.9% sensitivity, 98.5% specificity, 82% PPV, and 99.3% NPV. The composite scores of the NLP algorithm were 0.89 (F-score) and 0.85 (MCC). The prevalences of PHN in the validation data were 6.9% (reference standard), 7.6% (NLP), and 5.4%-13.1% (code-based). The code-based methods achieved a 52.7%-61.8% sensitivity, 89.8%-98.4% specificity, 27.6%-72.1% PPV, and 96.3%-97.1% NPV. The F-scores and MCCs ranged between 0.45 and 0.59 and between 0.32 and 0.61, respectively. Conclusions: The automated NLP-based approach identified PHN cases from the EHR with good accuracy. This method could be useful in population-based PHN research.

Comparative Effectiveness of Licensed Influenza Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the 2022-2023 Influenza Season Among Adults ≥65 Years of Age.

BACKGROUND: Influenza causes substantial morbidity, particularly among older individuals. Updated data on the effectiveness of currently licensed vaccines in this population are needed. METHODS: At Kaiser Permanente Southern California, we conducted a retrospective cohort study to evaluate comparative vaccine effectiveness (cVE) of high-dose (HD), adjuvanted, and standard-dose (SD) cell-based influenza vaccines, relative to the SD egg-based vaccine. We included adults aged ≥65 years who received an influenza vaccine between 1 August 2022 and 31 December 2022, with follow-up up to 20 May 2023. Primary outcomes were: (1) influenza-related medical encounters and (2) polymerase chain reaction (PCR)-confirmed influenza-related hospitalization. Adjusted hazard ratios (aHR) were estimated by Cox proportional hazards regression, adjusting for confounders using inverse probability of treatment weighting (IPTW). cVE (%) was calculated as (1-aHR) × 100 when aHR ≤1, and ([1/aHR]-1) × 100 when aHR >1. RESULTS: Our study population (n = 495 119) was 54.9% female, 46.3% non-Hispanic White, with a median age of 73 years (interquartile range [IQR] 69-79). Characteristics of all groups were well balanced after IPTW. Adjusted cVEs against influenza-related medical encounters in the HD, adjuvanted, and SD cell-based vaccine groups were 9.1% (95% confidence interval [CI]: .9, 16.7), 16.9% (95% CI: 1.7, 29.8), and -6.3 (95% CI: -18.3, 6.9), respectively. Adjusted cVEs against PCR-confirmed hospitalization in the HD, adjuvanted, and SD cell-based groups were 25.1% (95% CI: .2, 43.8), 61.6% (95% CI: 18.1, 82.0), and 26.4% (95% CI: -18.3, 55.7), respectively. CONCLUSIONS: Compared to the SD egg-based vaccine, HD and adjuvanted vaccines conferred additional protection against influenza-related outcomes in the 2022-2023 season in adults ≥65 years. Our results provide real-world evidence of the comparative effectiveness of currently licensed vaccines.

Risk factors for recurrent urinary tract infections among women in a large integrated health care organization in the United States.

BACKGROUND: Urinary tract infections (UTIs) occur commonly and often recur. However, recent data on the epidemiology of recurrent UTI (rUTI) are scarce. METHODS: Between 01/01/2016-31/12/2020, index uncomplicated UTIs (uUTI) from office, emergency department (ED), hospital, and virtual care settings were identified from electronic health records of women at Kaiser Permanente Southern California. We defined rUTI as ≥3 UTI within 365 days or ≥2 UTI within 180 days. We determined the proportion of women with cystitis index uUTI who had rUTI and examined factors associated with rUTIs using modified multivariable Poisson regression. RESULTS: Among 374,171 women with cystitis index uUTI, 54,318 (14.5%) had rUTI. A higher proportion of women with rUTI compared to those without rUTI were age 18-27 or ≥78 years at index uUTI (19.7% vs 18.7% and 9.0% vs 6.0%, respectively), were immunocompromised, or had a positive urine culture at index uUTI. In multivariable analyses, characteristics associated with rUTI included younger or older age (48-57 vs 18-27 years aRR=0.83 [95% CI: 0.80-0.85]; ≥78 vs 18-27 years aRR=1.07 [95%CI=1.03-1.11]), Charlson Comorbidity Index (≥3 vs 0, aRR=1.12 [95%CI:1.08-1.17]), and diabetes mellitus (aRR=1.07 [95%CI:1.04-1.10]). More frequent prior year outpatient and ED encounters, oral antibiotic prescriptions, oral contraceptive prescriptions, positive culture at index uUTI, and antibiotic resistant organisms were also associated with increased risk of rUTI. CONCLUSIONS: The high risk of rUTI among women with cystitis is concerning, especially given previous reports of increasing UTI incidence. Current assessment of the epidemiology of rUTI may guide the development of preventive interventions against UTI.

Antibiotic resistance of urinary tract infection recurrences in a large U.S. integrated health care system.

BACKGROUND: Data on antibiotic resistance of uropathogens for UTI recurrences are lacking. METHODS: In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021. RESULTS: We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend <0.001), while the proportion due to Klebsiella spp increased from index UTI (7%) to UTI 6 (11%) (p-for-trend <0.001). Non-susceptibility to ≥1 and ≥3 antibiotic classes was observed in 57% and 13% of index uUTIs, respectively, and was higher for subsequent UTIs (65% and 20%, respectively, for UTI 6). Most commonly observed antibiotic non-susceptibility patterns included penicillins alone (12%), and penicillins, trimethoprim-sulfamethoxazole plus ≥1 additional antibiotic class (9%). CONCLUSIONS: Antibiotic non-susceptibility is common in UTIs and increases with subsequent UTIs. Continuous monitoring of UTI recurrences and susceptibility patterns are needed to guide treatment decisions.

Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages.

Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

Development of a University-Government Partnership for Public Health Response and Workforce Development in the State of Oregon.

The COVID-19 pandemic exposed and exacerbated a public health workforce shortage and national strategies have called for the development of clear occupational pathways for students to enter the public health workforce and meaningful public health careers. In response to the immediate need for public health workers during the pandemic, several universities and academic hospitals rapidly mobilized students and employees and partnered with local or state health departments. However, many of those partnerships were based on short-term volunteer effort to support critical COVID-19 public health efforts. In this article, we document the development of Oregon's Public Health Practice Team, a student, staff, and faculty workforce developed at the Oregon Health & Science University-Portland State University (OHSU-PSU) School of Public Health in close collaboration with the Oregon Health Authority (OHA). This project contributed significant effort to several phases of Oregon's statewide public health response to COVID-19, and over time developed into a lasting, multi-purpose, inter-agency collaborative public health practice program. Health equity has been centered at every stage of this work. We describe the phases of the partnership development, the current team structure and operations, and highlight key challenges and lessons learned. This provides a case-study of how an innovative and flexible university-government partnership can contribute to immediate pandemic response needs, and also support ongoing public health responses to emerging needs, while contributing to the development of a skilled and diverse public health workforce.

Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

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.

Tolerability Outcomes of American Thoracic Society/Infectious Diseases Society of America Guideline-Recommended Multidrug Antibiotic Treatment for Mycobacterium avium Complex Pulmonary Disease in US Medicare Beneficiaries With Bronchiectasis.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. RESEARCH QUESTION: Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation? STUDY DESIGN AND METHODS: In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens. RESULTS: The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). INTERPRETATION: Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD.

Prior Screening for Latent Tuberculosis Among Patients Diagnosed With Tuberculosis Disease: Missed Opportunities?

Background: California has the largest number of tuberculosis (TB) disease cases in the United States. This study in a large California health system assessed missed opportunities for latent tuberculosis (LTBI) screening among patients with TB disease. Methods: Kaiser Permanente Southern California patients who were ≥18 years old with membership for ≥24 months during the study period from 1 January 2008 to 31 December 2019 were included. Prior LTBI test (tuberculin skin test or interferon-γ release assay) or diagnosis code prior to TB disease diagnosis was assessed among patients with observed TB disease (confirmed by polymerase chain reaction and/or culture). In the absence of current treatment practices, more patients screened for LTBI may have developed TB disease. We estimated hypothetical TB disease cases prevented by multiplying LTBI progression rates by the number of LTBI-positive patients prescribed treatment. Results: A total of 1289 patients with observed TB disease were identified; 148 patients were LTBI positive and 84 were LTBI negative. Patients not prescreened for LTBI made up 82.0% of observed TB disease cases (1057/1289). Adding the hypothetical maximum estimate for prevented cases decreased the percentage of patients who were not prescreened for LTBI to 61.7% [1057/(1289 + 424)]. Conclusions: One-fifth of patients were screened for LTBI prior to their active TB diagnosis. Assuming the upper bound of cases prevented through current screening, almost 62% of TB disease patients were never screened for LTBI. Future work to elucidate gaps in LTBI screening practices and to identify opportunities to improve screening guidelines is needed.

mRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States.

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.

Risk of herpes zoster following mRNA COVID-19 vaccine administration.

BACKGROUND: Adverse events following mRNA COVID-19 vaccines, including herpes zoster (HZ), have been reported. We conducted a cohort study to evaluate the association between mRNA COVID-19 vaccination and subsequent HZ at Kaiser Permanente Southern California (KPSC). RESEARCH DESIGN AND METHODS: The vaccinated cohort consisted of KPSC members who received their first dose of mRNA COVID-19 vaccine (mRNA-1273 and BNT162b2) during 12/2020-05/2021 and were matched to unvaccinated individuals on age and sex. Incident HZ cases occurring within 90 days of follow-up were identified by diagnosis codes and antiviral medications. Cox proportional hazards models estimated adjusted hazard ratios (aHR), comparing HZ incidence between the vaccinated and unvaccinated cohorts. RESULTS: Cohort included 1,052,362 mRNA-1273 recipients, 1,055,461 BNT162b2 recipients, and 1,020,334 comparators. Compared to unvaccinated individuals, aHR for HZ up to 90 days after the second dose of mRNA-1273 and BNT162b2 was 1.14 (1.05-1.24) and 1.12 (1.03-1.22), respectively. In those aged ≥50 years not vaccinated with zoster vaccine, aHR was also increased after the second dose of mRNA-1273 (1.18 [1.06-1.33]) and BNT162b2 (1.15 [1.02-1.29]) vaccine vs. unvaccinated individuals. CONCLUSIONS: Our findings suggest a potential increased risk of HZ after a second dose of mRNA vaccines, potentially driven by the increased risk in individuals aged ≥50 years without history of zoster vaccination.

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.

Effectiveness of a fourth dose of mRNA-1273 against COVID-19 among older adults in the United States: Interim results from an observational cohort study.

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased 2-4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time.

Impact of California's Senate Bill 27 on Antimicrobial-Resistant Escherichia coli Urinary Tract Infection in Humans: Protocol for a Study of Methods and Baseline Data.

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. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45109.

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study.

BACKGROUND: Data on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population. METHODS: We conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals. RESULTS: We included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021-12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8-58.9 %), 83.0 % (75.4-88.3 %), and 87.1 % (30.6-97.6 %), respectively. CONCLUSION: Three doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.

Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5.

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against omicron BA.4/BA.5 compared with earlier omicron subvariants. This test-negative case-control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.

Effectiveness of Messenger RNA-1273 Vaccine Booster Against Coronavirus Disease 2019 in Immunocompetent Adults.

BACKGROUND: We conducted a prospective cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of a booster dose vs 2-dose primary series of messenger RNA (mRNA)-1273 in immunocompetent individuals. METHODS: Immunocompetent adults who received a booster dose of mRNA-1273 from October 2021 through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second-dose date and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), comparing outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and coronavirus disease 2019 [COVID-19] hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1 - aHR) × 100. aHRs and rVE were also estimated by subgroup and month of follow-up. RESULTS: The study included 431 328 booster-dose vaccinated adults matched to 431 328 2-dose vaccinated adults. rVE was 61.3% (95% CI: 60.5%-62.2%) against SARS-CoV-2 infection, 89.0% (86.2%-91.2%) against COVID-19 hospitalization, and 96.0% (68.0%-99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0 to <1 month of follow-up) to 30.5% (2 to <3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0 to <1 month) to 78.7% (2 to <3 months). CONCLUSIONS: Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared with the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

Treatment of Nontuberculous Mycobacterial (NTM) Pulmonary Infection in the US Bronchiectasis and NTM Registry: Treatment Patterns, Adverse Events, and Adherence to American Thoracic Society/Infectious Disease Society of America Treatment Guidelines.

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy.