Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study.

BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection. METHODS: In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score. RESULTS: Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006. CONCLUSIONS: Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.

Risk stratification for colorectal cancer in individuals with subtypes of serrated polyps.

OBJECTIVE: The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood. DESIGN: This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression. RESULTS: Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8). CONCLUSION: Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.

Increased Risk of Colorectal Cancer in Individuals With a History of Serrated Polyps.

BACKGROUND AND AIMS: Serrated polyp (SPs) are precursors to 20% to 30% of cases of colorectal tumors, but patients' long-term risk after removal of SPs is poorly understood. We investigated the risk of colorectal cancer (CRC) in individuals with a history of SPs. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent colonoscopy from 2006 through 2016. Study participants were categorized based on the size and location of SPs. We used Cox proportional hazards modeling to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association of CRC diagnosed more than 1 year after colonoscopy, with polyp type vs no polyp after adjustment for year of colonoscopy, age, sex, race/ethnicity, and smoking history. RESULTS: The study included 233,393 individuals, of whom 445 developed incident CRC. At 10 years, the cumulative incidence rates of CRC for individuals with no polyp, proximal small SPs, proximal large SPs, and distal SPs were 4.7 (95% CI, 4.0-5.6), 14.8 (95% CI, 9.0-24.3), 30.2 (95% CI, 13.2-68.4), and 5.9 (95% CI, 3.6-9.5) per 1000 persons, respectively. In patients with SPs, risk of CRC was not increased until 3 years or more after the first colonoscopy (HR for small proximal SPs 2.6; 95% CI, 1.7-3.9 and HR for large proximal SPs 8.0; 95% CI, 3.6-16.1). The presence of synchronous adenomas increased the risk for CRC (HR for proximal SPs with synchronous adenomas 4.0; 95% CI, 3.0-5.5 and HR for distal SPs with synchronous adenomas 2.4; 95% CI, 1.7-3.4). CONCLUSIONS: In a retrospective analysis of a large cohort of individuals examined by colonoscopy, we found that risk of incident CRC increased in individuals with proximal SPs (large SPs in particular) 3 years or more after the colonoscopy. These findings support guidelines that recommend surveillance colonoscopy for individuals with SPs.

Development of an algorithm to detect methotrexate wrong frequency error using computerized health care data.

PURPOSE: We validated an algorithm to detect frequency errors in computerized healthcare data and estimated the incidence of these errors in an integrated healthcare system. METHODS: We applied Sentinel System analytic tools on the electronic health records of Kaiser Permanente, Northern California, January 1, 2010, through May 30, 2015,to identify rheumatoid arthritis (RA) patients with new use of methotrexate (365-day baseline period). We identified potential methotrexate frequency errors using ICD-9 code 995.20 (adverse drug event), Current Procedural Terminology (CPT) code 96409 for injection of leucovorin and prescription refill patterns. We performed chart review to confirm the frequency errors, assessed performance for detecting frequency errors, and estimated the incidence of chart-confirmed errors. RESULTS: The study included 24,529 methotrexate dispensings among 3,668 RA patients. Among these, 722 (3%) had one dispensing and 23,807 (97.1%) had ≥2 dispensings during 1-year follow-up period. We flagged 653 (2.7%) with a potential medication error (46 with one dispensing and 607 with ≥2 dispensings). We sampled 94 for chart review, and confirmed three methotrexate errors. All three confirmed frequency errors involved a first methotrexate dispensing followed by injected rescue therapy, leucovorin, (positive predictive value, 60%; 95% confidence interval [CI], 15-95%). No potential errors were found among patients with ≥2 dispensings. We estimated the frequency error incidence among one methotrexate dispensing to be 0.4% (95%CI, 0.1% to 1.2%). CONCLUSION: Rescue therapy is a specific indicator of methotrexate overdose among first methotrexate dispensings. This method is generalizable to other medications with serious adverse events treated with antidotes.

Natural language processing to ascertain two key variables from operative reports in ophthalmology.

PURPOSE: Antibiotic prophylaxis is critical to ophthalmology and other surgical specialties. We performed natural language processing (NLP) of 743 838 operative notes recorded for 315 246 surgeries to ascertain two variables needed to study the comparative effectiveness of antibiotic prophylaxis in cataract surgery. The first key variable was an exposure variable, intracameral antibiotic injection. The second was an intraoperative complication, posterior capsular rupture (PCR), which functioned as a potential confounder. To help other researchers use NLP in their settings, we describe our NLP protocol and lessons learned. METHODS: For each of the two variables, we used SAS Text Miner and other SAS text-processing modules with a training set of 10 000 (1.3%) operative notes to develop a lexicon. The lexica identified misspellings, abbreviations, and negations, and linked words into concepts (e.g. "antibiotic" linked with "injection"). We confirmed the NLP tools by iteratively obtaining random samples of 2000 (0.3%) notes, with replacement. RESULTS: The NLP tools identified approximately 60 000 intracameral antibiotic injections and 3500 cases of PCR. The positive and negative predictive values for intracameral antibiotic injection exceeded 99%. For the intraoperative complication, they exceeded 94%. CONCLUSION: NLP was a valid and feasible method for obtaining critical variables needed for a research study of surgical safety. These NLP tools were intended for use in the study sample. Use with external datasets or future datasets in our own setting would require further testing. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized. METHODS: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey. RESULTS: Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness. CONCLUSIONS: In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS.

SARS-CoV-2 Omicron subvariant genomic variation associations with immune evasion in Northern California: A retrospective cohort study.

Background: The possibility of association between SARS-CoV-2 genomic variation and immune evasion is not known among persons with Omicron variant SARS-CoV-2 infection. Methods: In a retrospective cohort, using Poisson regression adjusting for sociodemographic variables and month of infection, we examined associations between individual non-lineage defining mutations and SARS-CoV-2 immunity status, defined as a) no prior recorded infection, b) not vaccinated but with at least one prior recorded infection, c) complete primary series vaccination, and/or d) primary series vaccination and ≥ 1 booster. We identified all non-synonymous single nucleotide polymorphisms (SNPs), insertions and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. We also examined correlations between the presence of SNPs with each other, with subvariants, and over time. Results: Seventy-nine mutations met inclusion criteria. Among 15,566 persons infected with Omicron SARS-CoV-2, 1,825 (12%) were unvaccinated with no prior recorded infection, 360 (2%) were unvaccinated with a recorded prior infection, 13,381 (86%) had a complete primary series vaccination, and 9,172 (58%) had at least one booster. After examining correlation between SNPs, 79 individual non-lineage defining mutations were organized into 38 groups. After correction for multiple testing, no individual SNPs or SNP groups were significantly associated with immunity status levels. Conclusions: Genomic variation identified within SARS-CoV-2 Omicron specimens was not significantly associated with immunity status, suggesting that contribution of non-lineage defining SNPs to immune evasion is minimal. Larger-scale surveillance of SARS-CoV-2 genomes linked with clinical data can help provide information to inform future vaccine development.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

BACKGROUND: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine-induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. METHODS: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population-level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. RESULTS: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0-88.9) in May 2021 to 93.5% (CI 89.5-97.5) in April 2022. By April 2022, 68.5% (CI 61.9-74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7-17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5-14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1-7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. CONCLUSIONS: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine- induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population- level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. Results: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0-88.9) in May 2021 to 93.5% (CI 89.5-97.5) in April 2022. By April 2022, 68.5% (CI 61.9-74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7-17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5- 14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1-7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. Conclusions: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence. Article summary: By April 2022, >93% of people had antibodies to SARS-CoV-2 with COVID-19 vaccination as the main driver of overall population-level seroprevalence in our healthcare system. SARS-CoV-2 infection without vaccination made a small contribution to population-level seroprevalence in our healthcare system.

Real-World Evidence to Supplement Randomized Clinical Trials: Tocilizumab for Severe COVID-19 Pneumonia vs. a Cohort Receiving Standard of Care.

Randomized controlled trials (RCTs) remain the gold standard for evaluating treatment efficacy, but real-world evidence can supplement RCT results. Tocilizumab was not found to reduce 28-day mortality in a phase III, double-blind, placebo-controlled trial (COVACTA) among hospitalized patients with severe coronavirus disease 2019 (COVID-19) pneumonia. We created a real-world external comparator arm mirroring the COVACTA trial to confirm findings and assess the feasibility of using an external comparator arm to supplement an RCT. Eligible COVACTA participants in both the tocilizumab treatment and placebo arms were matched 1:1 using propensity score matching to persons without tocilizumab exposure in an external comparator arm. Adjusted Cox proportional hazard models estimated differences in 28-day mortality comparing COVACTA participants to matched external comparator arm participants. Patients in the COVACTA tocilizumab treatment arm had a similar risk of death compared with patients in the external comparator arm (hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.64-1.84) with similar estimated 28-day mortality in the COVACTA tocilizumab treatment arm compared with the external comparator arm (18%, 95% CI: 13-24 vs. 19%, 95% CI: 13-24, P > 0.9). COVACTA placebo treatment arm participants had a similar risk of mortality (adjusted HR: 0.69, 95% CI: 0.32-1.46) compared with the external comparator arm. Using an external comparator arm has the potential to supplement RCT data and support results of primary RCT analyses.

Effects of welfare and maternal work on recommended preventive care utilization among low-income children.

OBJECTIVES: We examined how maternal work and welfare receipt are associated with children receiving recommended pediatric preventive care services. METHODS: We identified American Academy of Pediatrics-recommended preventive care visits from medical records of children in the 1999-2004 Illinois Families Study: Child Well-Being. We used Illinois administrative data to identify whether mothers received welfare or worked during the period the visit was recommended, and we analyzed the child visit data using random-intercept logistic regressions that adjusted for child, maternal, and visit-specific characteristics. RESULTS: The 485 children (95%) meeting inclusion criteria made 41% of their recommended visits. Children were 60% more likely (adjusted odds ratios [AOR` = 1.60; 95% confidence interval [CI] = 1.27, 2.01) to make recommended visits when mothers received welfare but did not work compared with when mothers did not receive welfare and did not work. Children were 25% less likely (AOR = 0.75; 95% CI = 0.60, 0.94) to make preventive care visits during periods when mothers received welfare and worked compared with welfare only periods. CONCLUSION: The Temporary Assistance for Needy Families maternal work requirement may be a barrier to receiving recommended preventive pediatric health care.

Patient Experience and Satisfaction With Immediate Sequential and Delayed Sequential Bilateral Cataract Surgery.

PURPOSE: In bilaterally pseudophakic patients who received immediate or delayed sequential bilateral cataract surgery (ISBCS or DSBCS), we sought to determine patient experience, particularly related to the loss of opportunity to modify the surgical plan for the second eye. DESIGN: Cross-sectional. METHODS: Patients who received ISBCS (n = 1818) and DSBCS (n = 1818) in the Kaiser Permanente Northern California system between 2017 and 2019 who actively used the electronic patient portal were randomly selected and sent a survey link. The survey inquired about reasons for choosing ISBCS or DSBCS, concerns about surgery, and whether the loss of opportunity to modify the surgical plan for the second eye affected the patient's decision to undergo ISBCS. RESULTS: Participation was 18% among patients who received ISBCS and 17% among patients who received DSBCS. Of the patients who received ISBCS, 96% would choose ISBCS again while 80% of patients who received DSBCS would choose DSBCS again (P < .0001). Convenience was the leading reason patients chose ISBCS (65%), whereas surgeon recommendation was the primary reason patients chose DSBCS (68%). Sixteen percent of patients who received ISBCS and 38% of patients who received DSCBS reported that the possibility of modifying the surgical plan to reduce the need for corrective lenses in the second eye was an important consideration (P < .0001). CONCLUSIONS: Compared with patient who chose DSBCS, patients who chose ISBCS were more likely to choose ISBCS again and to recommend ISBCS to a family member or friend. The option to modify the surgical plan for the second eye to reduce need for glasses or contact lenses was not an important consideration for most of either group.

Development and validation of a prediction algorithm to identify birth in countries with high tuberculosis incidence in two large California health systems.

OBJECTIVE: Though targeted testing for latent tuberculosis infection ("LTBI") for persons born in countries with high tuberculosis incidence ("HTBIC") is recommended in health care settings, this information is not routinely recorded in the electronic health record ("EHR"). We develop and validate a prediction model for birth in a HTBIC using EHR data. MATERIALS AND METHODS: In a cohort of patients within Kaiser Permanente Southern California ("KPSC") and Kaiser Permanent Northern California ("KPNC") between January 1, 2008 and December 31, 2019, KPSC was used as the development dataset and KPNC was used for external validation using logistic regression. Model performance was evaluated using area under the receiver operator curve ("AUCROC") and area under the precision and recall curve ("AUPRC"). We explored various cut-points to improve screening for LTBI. RESULTS: KPSC had 73% and KPNC had 54% of patients missing country-of-birth information in the EHR, leaving 2,036,400 and 2,880,570 patients with EHR-documented country-of-birth at KPSC and KPNC, respectively. The final model had an AUCROC of 0.85 and 0.87 on internal and external validation datasets, respectively. It had an AUPRC of 0.69 and 0.64 (compared to a baseline HTBIC-birth prevalence of 0.24 at KPSC and 0.19 at KPNC) on internal and external validation datasets, respectively. The cut-points explored resulted in a number needed to screen from 7.1-8.5 persons/positive LTBI diagnosis, compared to 4.2 and 16.8 persons/positive LTBI diagnosis from EHR-documented birth in a HTBIC and current screening criteria, respectively. DISCUSSION: Using logistic regression with EHR data, we developed a simple yet useful model to predict birth in a HTBIC which decreased the number needed to screen compared to current LTBI screening criteria. CONCLUSION: Our model improves the ability to screen for LTBI in health care settings based on birth in a HTBIC.

Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19.

OBJECTIVES: Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Large integrated health system with 9 million members in California, USA. PARTICIPANTS: 4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV). INTERVENTIONS: Receipt of tocilizumab within 10 days of initiation of IMV. OUTCOME MEASURES: Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge. RESULTS: Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3-10 days after initiation of IMV. CONCLUSIONS: Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.

Risk of severe clinical outcomes among persons with SARS-CoV-2 infection with differing levels of vaccination during widespread Omicron (B.1.1.529) and Delta (B.1.617.2) variant circulation in Northern California: A retrospective cohort study.

Background: The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined. Methods: We conducted a retrospective cohort study to assess risks of severe clinical outcomes within 21 days after SARS-CoV-2 diagnosis in a large, diverse, integrated health system. Findings: Among 118,078 persons with incident SARS-CoV-2 infection, 48,101 (41%) were during the Omicron period and 69,977 (59%) during the Delta (B.1.617.2) period. Cumulative incidence of any hospitalization (2.4% versus 7.8%; adjusted hazard ratio [aHR] 0.55; 95% confidence interval [CI] (0.51-0.59), with low-flow oxygen support (1.6% versus 6.4%; aHR 0.46; CI 0.43-0.50), with high-flow oxygen support (0.6% versus 2.8%; aHR 0.47; CI 0.41-0.54), with invasive mechanical ventilation (0.1% versus 0.7%; aHR 0.43; CI 0.33-0.56), and death (0.2% versus 0.7%; aHR 0.54; CI 0.42-0.70) were lower in the Omicron than the Delta period. The risk of hospitalization was higher among unvaccinated persons (aHR 8.34; CI 7.25-9.60) and those who completed a primary COVID-19 vaccination series (aHR 1.72; CI 1.49-1.97) compared with those who completed a primary vaccination series and an additional dose. The strongest risk factors for all severe clinical outcomes were older age, higher body mass index and select comorbidities. Interpretation: Persons with SARS-CoV-2 infection were significantly less likely to develop severe clinical outcomes during the Omicron period compared with the Delta period. COVID-19 primary vaccination and additional doses were associated with reduced risk of severe clinical outcomes among those with SARS-CoV-2 infection. Funding: National Cancer Institute and The Permanente Medical Group.

Intraocular Pressure Reduction after Phacoemulsification: A Matched Cohort Study.

PURPOSE: Phacoemulsification has been linked to lowered intraocular pressure (IOP) in patients with glaucoma, ocular hypertension, anatomic narrow angles, and in glaucoma suspects, but the magnitude of change has varied. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with glaucoma treated from June 2010 through May 2015 who underwent phacoemulsification (surgical group) were matched to patients who did not (nonsurgical group) for age, gender, type of glaucoma, baseline IOP, and number and type of glaucoma medications. METHODS: Electronic medical record information was used to compare the matched surgical and nonsurgical groups. MAIN OUTCOME MEASURES: Change in IOP, change in number of glaucoma medications, and likelihood of a glaucoma procedure within 36 months after phacoemulsification. Intraocular pressure measures were obtained from Goldmann applanation tonometry when available (45%), and otherwise with the iCare tonometer (iCare USA, Raleigh, NC), the Tono-Pen (Reichert Technologies, Depew, NY), noncontact tonometry, and pneumotonometry. RESULTS: Among 16 169 matched pairs, average IOP after the index date was lower in the surgical than nonsurgical group throughout follow-up to 36 months. The difference was greatest during months 1 through 18, during which IOP increased by 0.22 mmHg from 16.49 mmHg in the average nonsurgical patient and decreased by 0.99 mmHg from 16.50 mmHg in the average surgical patient (difference in difference, 1.21 mmHg; 95% confidence interval [CI], 1.12-1.30 mmHg). The difference in difference was greatest for patients with ocular hypertension (2.00 mmHg) and for patients with preoperative IOP of 20 mmHg or more (2.46 mmHg). By 30 to 36 months, 5% (95% CI, 4%-6%) fewer surgical patients used an ophthalmic medication. In the surgical group, the odds of selective laser trabeculoplasty were reduced in patients with ocular hypertension (odds ratio [OR], 0.27; 95% CI, 0.10-0.74) or glaucoma suspects (OR, 0.31; 95% CI, 0.20-0.47), whereas the odds of glaucoma surgery were elevated in surgical patients with primary open-angle glaucoma (OR, 1.48; 95% CI, 1.08-2.01). CONCLUSIONS: The association of phacoemulsification for cataract with IOP reduction was lower than in past referral-based studies. Surgeons should expect to reduce IOP approximately 1 to 2 mmHg with phacoemulsification in patients with preoperative IOP of less than 20 mmHg.

Visual outcomes after cataract surgery: topical nonsteroidal anti-inflammatory drug prophylaxis compared with prednisolone.

PURPOSE: To compare visual outcomes in patients without a history of macular edema after phacoemulsification using combination topical nonsteroidal anti-inflammatory drug plus prednisolone with prednisolone alone. SETTING: Kaiser Permanente Northern California, USA. DESIGN: Retrospective cohort study. METHODS: Information was obtained from the electronic health record. The first measure of corrected distance visual acuity (CDVA) recorded during the period 3 weeks to 1 year after phacoemulsification was obtained. Confounding factors and clustering of eyes within patients were adjusted using linear mixed effects regression models for the continuous outcome of CDVA improvement and general estimating equations for the dichotomous outcome of 20/20 or better vs 20/25 or worse. RESULTS: The study included 62 700 health plan members of whom 26,309 (42%) used topical prednisolone alone, whereas 36,391 (58%) used combination treatment. The mean within-person change in CDVA from the preoperative measurement to the postoperative measurement was the same (-0.43 logMAR) for patients in the 2 groups. However, the group that received combination treatment was somewhat more likely to achieve CDVA of 20/20 or better (odds ratio 1.24 with 95% CI, 1.20-1.28). CONCLUSIONS: In this large study of cataract surgery patients, a small statistically significant association of combination treatment compared with prednisolone alone was observed.

Implementation of a Multidisciplinary Expert Testicular Cancer Tumor Board Across a Large Integrated Healthcare Delivery System Via Early Case Ascertainment.

PURPOSE: In 2016, Kaiser Permanente Northern California began regionalizing testicular cancer care using population-based tumor board review. This mixed methods evaluation describes implementation outcomes and learnings. METHODS: We conducted in-depth interviews with key stakeholders, administered surveys to local oncologists and urologists, and used clinical data to evaluate changes in care delivery during 2015-2018. RESULTS: An average of 135 patients with testicular cancer were diagnosed each year. Interviews with 16 key stakeholders provided several insights. Implementation resulted in high levels of satisfaction, was dependent on leadership and staff at various levels, and required technology and consulting solutions aligned to user agreements and clinical workflows. Of 123 local oncologists and urologists who completed surveys, 97% understood why care was regionalized and 89% agreed that tumor board review improved treatment decisions. Among 177 patients with stage I seminoma, the percentage appropriately observed rather than treated with adjuvant chemotherapy or radiation therapy increased from 48% (95% CI, 35 to 62) in 2015 to 87% (75 to 99) in 2018. Review altered care based on pathology and radiology re-review in 14.5 % of cases. CONCLUSION: Regionalization was feasible and effective.

The relationship between self-report and biomarkers of stress in low-income reproductive-age women.

OBJECTIVE: The purpose of this study was to determine whether there is an association between self-reported and biologic measures of stress in low-income, reproductive-age women. STUDY DESIGN: Between 1999 and 2005, randomly selected reproductive-age women from the 1998 welfare rolls in Chicago, IL, were interviewed yearly to assess psychosocial, socioeconomic, and health characteristics. The association of 2 stress-sensitive biomarkers (Epstein-Barr virus antibody titer (EBV) and C-reactive protein level) with self-reported stress was assessed. RESULTS: Of the 206 women who were interviewed, 205 women (99%) agreed to provide a blood sample. There was no difference in mean EBV or C-reactive protein levels based on age, race, parity, employment, marital status, or education. Women who reported a higher degree of perceived stress or reported experiences of discrimination had significantly higher levels of EBV (P < .05). CONCLUSION: Measures of self-reported psychosocial stress are associated with elevated levels EBV antibody in a low-income population of reproductive-age women.

Development and Validation of Machine Learning Models: Electronic Health Record Data To Predict Visual Acuity After Cataract Surgery.

BACKGROUND: To develop predictive models of final corrected distance visual acuity (CDVA) following cataract surgery using machine learning algorithms and electronic health record data. METHODS: In this predictive modeling study we used decision tree, random forest, and gradient boosting. We included the first surgical eye of 64,768 members of Kaiser Permanente Northern California who underwent cataract surgery from June 1, 2010 through May 31, 2015. We measured discrimination and calibration of machine learning models for predicting postoperative CDVA 20/50 or worse vs 20/40 or better. RESULTS: The training set included 51,712 patients, and the validation set included 13,056 patients. We compared 3 machine learning models and found that the gradient boosting model provided the best discrimination ability for CDVA. The most important variables for predicting final CDVA 20/50 or worse were preoperative CDVA, age, and age-related macular degeneration, which together accounted for 41% of the gain in optimization of the gradient boosting model. Other important variables in the model included dispensed glaucoma medication, epiretinal membrane, cornea disorder, cataract surgery operating time, surgeon experience, and census block neighborhood characteristics (household income, family income, family poverty, college education, and home residence by owner). CONCLUSION: For predicting CDVA after cataract surgery, gradient boosting had the best ability to discriminate patients with postoperative CDVA 20/50 or worse from patients with postoperative CDVA 20/40 or better. Machine learning has the potential to improve prognosis and can improve patient information when making decisions to undergo cataract surgery.