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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 ( = 469,789).

β-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 β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned 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.

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.

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).

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.

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.

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

Purpose: The early period after chronic kidney disease (CKD) patients transition to end-stage renal disease (ESRD) represents the highest mortality risk but is variable among different patient populations and clinical circumstances. We compared early mortality outcomes among a diverse CKD population that transitioned to ESRD.

Methods: A retrospective cohort study (1/1/2002 through 12/31/2013) of CKD patients (age ≥ 18 years) who transitioned to peritoneal dialysis (PD), hemodialysis (HD) with arteriovenous fistula/grafts, and HD with catheters was performed.