The Effect of Neonatal Sepsis on Risk of Autism Diagnosis.

OBJECTIVE: The study aimed to examine the association between neonatal sepsis and autism risk among children and whether the risk varied with the timing of exposure, child's sex, and race/ethnicity. STUDY DESIGN: We conducted a retrospective cohort study using electronic health records (EHR) extracted from Kaiser Permanente Southern California Health Care System. Mother-child dyads were constructed by linking records of children born to member mothers and continuing to receive care through the system during the follow-up period with those of their biological mothers (n = 469,789). Clinical health records were used to define neonatal sepsis. Diagnosis of autism was made by medical specialists. Potential confounders included maternal sociodemographic factors, obstetrical history, child's age, sex, race/ethnicity, and maternal and child medical history. Incident rates and adjusted hazard ratios (aHR) were used to estimate the associations. RESULTS: Compared with children without the diagnosis of autism, children with the condition were more likely to be from Asian/Pacific Islander descent and male sex. Exposed children showed higher rates of autism as compared with unexposed children (3.43 vs. 1.73 per 1,000 person-years, aHR: 1.67-95% confidence interval [CI]: 1.39-2.00). Both preterm (aHR: 1.47; 95% CI: 1.09-1.98) and term (aHR: 1.63; 95% CI: 1.29-2.06) births were associated with increased risk for autism. Although the magnitude of the HRs and incidence ratios for neonatal sepsis to increase autism risk varied between race ethnicities, neonatal sepsis was associated with significantly increased likelihood of autism diagnosis for all race-ethic groups except for Asian/Pacific Islanders. Although neonatal sepsis was associated with significantly increased autism risk for both boys and girls, incident rates and HR point estimates suggested that the effect may be stronger in girls. CONCLUSION: Neonatal sepsis is associated with increased risk of autism diagnosis in preterm- and term-born children. The association was significant for both girls and boys and all race ethnicities except for Asian-Pacific Islanders. KEY POINTS: · Neonatal sepsis is associated with increased risk of autism diagnosis.. · The association was significant in preterm- and term-born children.. · The association was significant for all race/ethnicities except for Asian-Pacific Islanders..

Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System.

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC). METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined. RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%. CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.

ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.

BACKGROUND: Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. OBJECTIVE: To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PATIENTS: Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. MEASUREMENTS: Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. RESULTS: Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m2, those with BMIs of 40 to 44 kg/m2 and greater than 45 kg/m2 had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected. LIMITATION: Deaths occurring outside a health care setting and not captured in membership files may have been missed. CONCLUSION: Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention. PRIMARY FUNDING SOURCE: Roche-Genentech.

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Religious Involvement and Telomere Length in Women Family Caregivers.

Telomere length (TL) is an indicator of cellular aging associated with longevity and psychosocial stress. We examine here the relationship between religious involvement and TL in 251 stressed female family caregivers recruited into a 2-site study. Religious involvement, perceived stress, caregiver burden, depressive symptoms, and social support were measured and correlated with TL in whole blood leukocytes. Results indicated a U-shaped relationship between religiosity and TL. Those scoring in the lowest 10% on religiosity tended to have the longest telomeres (5743 bp ± 367 vs. 5595 ± 383, p = 0.069). However, among the 90% of caregivers who were at least somewhat religious, religiosity was significantly and positively related to TL after controlling for covariates (B = 1.74, SE = 0.82, p = 0.034). Whereas nonreligious caregivers have relatively long telomeres, we found a positive relationship between religiosity and TL among those who are at least somewhat religious.

Religious vs. conventional cognitive behavioral therapy for major depression in persons with chronic medical illness: a pilot randomized trial.

We examine the efficacy of conventional cognitive behavioral therapy (CCBT) versus religiously integrated CBT (RCBT) in persons with major depression and chronic medical illness. Participants were randomized to either CCBT (n = 67) or RCBT (n = 65). The intervention in both groups consisted of ten 50-minute sessions delivered remotely during 12 weeks (94% by telephone). Adherence to treatment was similar, except in more religious participants in whom adherence to RCBT was slightly greater (85.7% vs. 65.9%, p = 0.10). The intention-to-treat analysis at 12 weeks indicated no significant difference in outcome between the two groups (B = 0.33; SE, 1.80; p = 0.86). Response rates and remission rates were also similar. Overall religiosity interacted with treatment group (B = -0.10; SE, 0.05; p = 0.048), suggesting that RCBT was slightly more efficacious in the more religious participants. These preliminary findings suggest that CCBT and RCBT are equivalent treatments of major depression in persons with chronic medical illness. Efficacy, as well as adherence, may be affected by client religiosity.

Increased vaccine sensitivity of an emerging SARS-CoV-2 variant.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome.

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43-69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.

Rationale & Objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. Study Design: Retrospective cohort study. Setting & Population: Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m2) with and without heart failure in a large integrated health care system in Southern California. Exposure: Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). Outcomes: All-cause and cardiovascular-related mortality within one year of CKD identification. Analytical Approach: HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. Results: The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). Limitations: Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. Conclusions: Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.

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.

Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system.

BACKGROUND: In the United States, oral nirmatrelvir-ritonavir (PaxlovidTM) is authorized for use among patients aged 12+ years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under current real-world prescribing practices in outpatient settings is unclear. METHODS: We undertook a matched observational cohort study of non-hospitalized cases with SARS-CoV-2 infection to compare outcomes among those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Cases were matched on testing date, age, sex, clinical status (including care received, presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination, Charlson comorbidity index, prior-year healthcare utilization, and body mass index. Primary analyses evaluated effectiveness of nirmatrelvir-ritonavir in preventing hospital admission or death within 30 days after a positive test. Secondary analyses evaluated effectiveness against intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])*100%, estimating the aHR via Cox proportional hazards models. RESULTS: Analyses included 7,274 nirmatrelvir-ritonavir recipients and 126,152 non-recipients with positive results from SARS-CoV-2 tests undertaken in outpatient settings between 8 April and 7 October, 2022. Overall, 114,208 (85.6%) and 81,739 (61.3%) of 133,426 participants had received 2+ and 3+ COVID-19 vaccine doses, respectively. A total of 111,489 (83.6% of 133,426) cases were symptomatic at the point of testing, with 5,472 (75.2% of 7,274) treatment recipients and 84,657 (67.1% of 126,152) non-recipients testing within 0-5 days after symptom onset. Effectiveness in preventing hospital admission or death within 30 days after a positive test was 79.6% (95% confidence interval: 33.9% to 93.8%) for cases dispensed nirmatrelvir-ritonavir within 0-5 days after symptom onset; within the subgroup of cases tested 0-5 days after symptom onset and dispensed treatment on the day of their test, effectiveness was 89.6% (50.2% to 97.8%). Effectiveness declined to 43.8% (-33.3% to 81.7%) for treatment course dispensed 6+ days after symptom onset or to cases who were not experiencing acute clinical symptoms. Overall, for cases dispensed treatment at any time within their clinical course, effectiveness was 53.6% (6.6% to 77.0%). Effectiveness in preventing the secondary endpoint of intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test was 89.2% (-25.0% to 99.3%) for cases dispensed treatment 0-5 days after symptom onset and 84.1% (18.8% to 96.9%) for cases dispensed treatment at any time. Subgroup analyses identified similar effectiveness estimates among cases who had received 2+ or 3+ COVID-19 vaccine doses. IMPLICATIONS: In a setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0-5 days after symptom onset was associated with substantial reductions in risk of hospital admission or death within 30 days after a positive outpatient SARS-CoV-2 test.

Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system.

BACKGROUND: In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. METHODS: In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. FINDINGS: 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8). INTERPRETATION: In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test. FUNDING: US Centers for Disease Control and Prevention and US National Institutes of Health.

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.

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.

Natural Language Processing for Improved Characterization of COVID-19 Symptoms: Observational Study of 350,000 Patients in a Large Integrated Health Care System.

BACKGROUND: Natural language processing (NLP) of unstructured text from electronic medical records (EMR) can improve the characterization of COVID-19 signs and symptoms, but large-scale studies demonstrating the real-world application and validation of NLP for this purpose are limited. OBJECTIVE: The aim of this paper is to assess the contribution of NLP when identifying COVID-19 signs and symptoms from EMR. METHODS: This study was conducted in Kaiser Permanente Southern California, a large integrated health care system using data from all patients with positive SARS-CoV-2 laboratory tests from March 2020 to May 2021. An NLP algorithm was developed to extract free text from EMR on 12 established signs and symptoms of COVID-19, including fever, cough, headache, fatigue, dyspnea, chills, sore throat, myalgia, anosmia, diarrhea, vomiting or nausea, and abdominal pain. The proportion of patients reporting each symptom and the corresponding onset dates were described before and after supplementing structured EMR data with NLP-extracted signs and symptoms. A random sample of 100 chart-reviewed and adjudicated SARS-CoV-2-positive cases were used to validate the algorithm performance. RESULTS: A total of 359,938 patients (mean age 40.4 [SD 19.2] years; 191,630/359,938, 53% female) with confirmed SARS-CoV-2 infection were identified over the study period. The most common signs and symptoms identified through NLP-supplemented analyses were cough (220,631/359,938, 61%), fever (185,618/359,938, 52%), myalgia (153,042/359,938, 43%), and headache (144,705/359,938, 40%). The NLP algorithm identified an additional 55,568 (15%) symptomatic cases that were previously defined as asymptomatic using structured data alone. The proportion of additional cases with each selected symptom identified in NLP-supplemented analysis varied across the selected symptoms, from 29% (63,742/220,631) of all records for cough to 64% (38,884/60,865) of all records with nausea or vomiting. Of the 295,305 symptomatic patients, the median time from symptom onset to testing was 3 days using structured data alone, whereas the NLP algorithm identified signs or symptoms approximately 1 day earlier. When validated against chart-reviewed cases, the NLP algorithm successfully identified signs and symptoms with consistently high sensitivity (ranging from 87% to 100%) and specificity (94% to 100%). CONCLUSIONS: These findings demonstrate that NLP can identify and characterize a broad set of COVID-19 signs and symptoms from unstructured EMR data with enhanced detail and timeliness compared with structured data alone.

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.

Association between seasonal influenza vaccination with pre- and postnatal outcomes.

OBJECTIVE: Influenza vaccination during pregnancy is known to prevent severe influenza illness but its effects on other outcomes and the extent to which its safety is affected by timing of vaccination, maternal race/ethnicity and the type of vaccine is less clear. Therefore, we examined this in a large retrospective cohort. METHODS: We analyzed medical and vaccination records from the Kaiser Permanente Southern California (KPSC) records and from the Kaiser Immunization Tracking System (2008-2016). The study included women who were pregnant with singletons during the influenza season. Odds ratios (OR) and their 95% confidence intervals (CI) were used to quantify the associations between immunization status during pregnancy and prenatal and postnatal outcomes after adjusting for confounders. RESULTS: Of the 247,036 women in these analyses, 53% were vaccinated during their pregnancy. No association between influenza vaccination during pregnancy and adverse prenatal and neonatal outcomes were observed. Influenza vaccination is associated with reduced risk of influenza (OR: 0.49, 95% CI: 0.39-0.62), maternal fever (OR: 0.40, 95% CI: 0.35-0.45), preeclampsia (OR: 0.93, 95% CI: 0.90-0.96), placental abruption (OR: 0.89, 95% CI: 0.82-0.96), stillbirth (OR: 0.88, 95% CI: 0.78-0.99), and NICU admission (OR: 0.89, 95% CI: 0.87-0.92). Both active and inactive vaccines were found to be safe in vaccinated pregnant women regardless of timing of vaccination. CONCLUSIONS: This study found no evidence of adverse maternal and infant outcomes associated with seasonal influenza vaccine during pregnancy. On the contrary, vaccinated women were less likely to have adverse outcomes than unvaccinated women. The lack of increased adverse outcomes associated with influenza vaccination suggests that the benefits of vaccination during pregnancy to the woman and her child far outweigh any risk, if there is one, from the vaccination.

Early Mortality Among Peritoneal Dialysis and Hemodialysis Patients Who Transitioned With an Optimal Outpatient Start.

INTRODUCTION: Lower early mortality observed in peritoneal dialysis (PD) compared with hemodialysis (HD) may be due to differential pre-end-stage renal disease (ESRD) care and the stable setting of transition to dialysis where PD starts are more frequently outpatient rather than during an unscheduled hospitalization. To account for these circumstances, we compared early mortality among a matched cohort of PD and HD patients who had optimal and outpatient starts. METHODS: Retrospective cohort study performed among patients with chronic kidney disease (CKD) who transitioned to ESRD from 1 January 2002 to 31 March 2015 with an optimal start in an outpatient setting. Optimal start defined as (i) HD with an arteriovenous graft or fistula or (ii) PD. Propensity score modeling factoring age, race, sex, comorbidities, estimated glomerular filtration rate (eGFR) level, and change in eGFR before ESRD was used to create a matched cohort of HD and PD. All-cause mortality was compared at 6 months, 1 year, and 2 years posttransition to ESRD. RESULTS: Among 2094 patients (1398 HD and 696 PD) who had optimal outpatient transition to ESRD, 541 HD patients were propensity score-matched to 541 PD patients (caliper distance <0.001). All-cause mortality odds ratios (OR) in PD compared with HD were 0.79 (0.39-1.63), 0.73 (0.43-1.23), and 0.88 (0.62-1.26) for 6 months, 1 year, and 2 years, respectively. Time-varying analysis accounting for modality switch (19% PD, 1.9% HD) demonstrated a mortality hazard ratio of 0.94 (0.70-1.24). CONCLUSION: Among an optimal start CKD cohort that transitioned to ESRD on an outpatient basis, we found no evidence of differences in early mortality between PD and HD.

Correction to: Disparities in early mortality among chronic kidney disease patients who transition to peritoneal dialysis and hemodialysis with and without catheters.

In the original publication, age stratified mortality rates were incorrectly added in Fig. 2. The correct Fig. 2 is given below.