Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants

Background The recently emerged SARS-CoV-2 omicron variant raised concerns around potential escape from vaccine-elicited immunity. Limited data are available on real-world vaccine effectiveness (VE) of mRNA-1273 against omicron. Here, we report VE of 2 or 3 mRNA-1273 doses against infection and hospitalization with omicron and delta, including among immunocompromised individuals. Methods This test negative study was conducted at Kaiser Permanente Southern California. Cases were individuals aged ≥18 years testing positive by RT-PCR with specimens collected between 12/6/2021 and 12/23/2021 with variant determined by spike gene status. Randomly sampled test negative controls were 5:1 matched to cases by age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression models were used to evaluate adjusted odds ratio (aOR) of vaccination with mRNA-1273 doses between cases and controls. VE(%) was calculated as (1-aOR)x100. Results 6657 test positive cases (44% delta, 56% omicron) were included. The 2-dose VE against omicron infection was 30.4% (95% CI, 5.0%-49.0%) at 14-90 days after vaccination and declined quickly thereafter. The 3-dose VE was 95.2% (93.4%-96.4%) against delta infection and 62.5% (56.2%-67.9%) against omicron infection. The 3-dose VE against omicron infection was low among immunocompromised individuals (11.5%; 0.0%-66.5%). None of the cases (delta or omicron) vaccinated with 3 doses were hospitalized compared to 53 delta and 2 omicron unvaccinated cases. Conclusions VE of 3 mRNA-1273 doses against infection with delta was high and durable, but VE against omicron infection was lower. VE against omicron infection was particularly low among immunocompromised individuals. No 3-dose recipients were hospitalized for COVID-19.

Comparison of Mammography Artificial Intelligence Algorithms for 5-year Breast Cancer Risk Prediction

PURPOSE: To examine the ability of 5 artificial intelligence (AI)-based computer vision algorithms, most trained to detect visible breast cancer on mammograms, to predict future risk relative to the Breast Cancer Surveillance Consortium clinical risk prediction model (BCSC v2). PATIENTS AND METHODS: In this case-cohort study, women who had a screening mammogram in 2016 at Kaiser Permanente Northern California with no evidence of cancer on final imaging assessment were followed through September 2021. Women with prior breast cancer or a known highly penetrant gene mutation were excluded. From the 329,814 total eligible women, a random subcohort of 13,881 women (4.2%) were selected, of whom 197 had incident cancer. All 4,475 additional incident cancers were also included. Continuous AI-predicted scores were generated from the index 2016 mammogram. Risk estimates were generated with the Kaplan-Meier method and time-varying area under the curve [AUC(t)]. RESULTS: For incident cancers at 0-1 year (interval cancer risk), BCSC demonstrated an AUC(t) of 0.62 (95% CI, 0.58-0.66), and the AI algorithms had AUC(t)s ranging from 0.66-0.71, all significantly higher than BCSC (P < .05). For incident cancers at 1 to 5 years (5-year future cancer risk), BCSC demonstrated an AUC(t) of 0.61 (95% CI, 0.60-0.62), and the AI algorithms had AUC(t)s ranging from 0.63 to 0.67, all significantly higher than BCSC. Combined BCSC and AI models demonstrated AUC(t)s for interval cancer risk of 0.67-0.73 and for 5-year future cancer risk of 0.66-0.68. CONCLUSION: The AI mammography algorithms we evaluated had significantly higher discrimination than the BCSC clinical risk model for interval and 5-year future cancer risk. Combined AI and BCSC models had slightly higher discrimination than AI alone.

Durability of mRNA-1273 against COVID-19 in the time of Delta: Interim results from an observational cohort study

Background: We conducted a prospective cohort study at Kaiser Permanente Southern California to study the vaccine effectiveness (VE) of mRNA-1273 over time and during the emergence of the Delta variant. Methods: The cohort for this planned interim analysis consisted of individuals aged ≥18 years receiving 2 doses of mRNA-1273 through June 2021, matched 1:1 to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through September 2021. Outcomes were SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) comparing outcomes in the vaccinated and unvaccinated groups. Adjusted VE (%) was calculated as (1-aHR)x100. HRs and VEs were also estimated for SARS-CoV-2 infection by age, sex, race/ethnicity, and during the Delta period (June-September 2021). VE against SARS-CoV-2 infection and COVID-19 hospitalization was estimated at 0-<2, 2-<4, 4-<6, and 6-<8 months post-vaccination. Results: 927,004 recipients of 2 doses of mRNA-1273 were matched to 927,004 unvaccinated individuals. VE (95% CI) was 82.8% (82.2-83.3%) against SARS-CoV-2 infection, 96.1% (95.5-96.6%) against COVID-19 hospitalization, and 97.2% (94.8-98.4%) against COVID-19 hospital death. VE against SARS-CoV-2 infection was similar by age, sex, and race/ethnicity, and was 86.5% (84.8-88.0%) during the Delta period. VE against SARS-CoV-2 infection decreased from 88.0% at 0-<2 months to 75.5% at 6-<8 months. Conclusions: These interim results provide continued evidence for protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period, and against COVID-19 hospitalization and hospital death.

STAR Caregivers: Virtual Training and Followup: Implementation

STAR Caregivers is an evidence-based intervention designed to reduce caregiver burden for caregivers of people living with dementia. This study translated the paper-based, face-to-face intervention into a 6-session, self-directed online learning program supported by 6, 30-minute telephone calls with a clinically trained coach. Our approach is designed to overcome issues of access to training. Eligible caregiver-patient dyads at Kaiser Permanente Washington were identified automatically via electronic health records. Qualitative interviews were conducted with a sample of patients to elicit information about their needs and preferences for training. We developed a “learning management system” (analogous to compliance training modules) complete with slides, voice-over narration, and testing. The training sessions are mounted on the KP Learn site and accessible to anyone. Baseline and outcomes data on standardized instruments are collected remotely via REDCap. Recruitment for the study is ongoing and initial participant feedback on the program is very positive.

65 & Thrive: Improving Patient Length of Stay, Readmission, and Quality of Care by Becoming an Age-Friendly Hospital

Data indicates that older persons will increase in numbers along with having an increase of life expectancy in the United States. Kaiser Permanente Los Angeles Medical Center’s Utilization Department developed “65 & Thrive”—an age-specialized initiative to provide holistic care that preserves independence, quality of life, prevents functional and cognitive decline, and promotes both patients and their families to continue thriving. The initiative’s focus is guided by the 5 M’s model on mobility, medication, mentation, multi-morbidity, and what matters. Case management staff were given age-sensitivity trainings, improved workflows and made assessments that identified, addressed, and secured resources for patients throughout their hospitalization. Silver Angel volunteers were specially trained to prevent physical and mental decline and focused on activities to prevent delirium, depression and falls. The volunteers visited with patients daily for these interactions. The initiative was piloted in April 2020 on a stroke telemetry unit and since then the hospital has seen a significant decrease in the overall annual readmission rates by 3.1% when compared to 2019. The average length of stay for older adult patients; however, increased from 4.05 to 4.83 days unfortunately due to COVID-19. This initiative demonstrates the necessity to expand “65 & Thrive” throughout the hospital and ultimately to other Kaiser Permanente medical centers to best provide holistic care to older adults.

Management of well appearing infants born to afebrile mothers with inadequate GBS prophylaxis: A retrospective comparison of the three approaches recommended by the COFN

BACKGROUND: There are three different approaches set forth by the Committee on the Fetus and Newborn (COFN) for managing asymptomatic neonates born to mothers with inadequate intrapartum antibiotic prophylaxis (IAP) for early-onset Group B Strep (GBS) infection. The first approach is that of categorical risk factor assessments, and recommends that asymptomatic infants born to afebrile mothers with inadequate IAP for GBS be monitored with clinical observation for 36–48 hours. The second approach recommends serial physical examinations and vital signs for 36–48 hours to closely monitor changes in clinical condition for all patients. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, a multivariate risk assessment, and it takes into consideration several perinatal risk factors. This multivariate risk assessment then provides recommendations for reassessment and management based on presume risk of the infant developing or having Early Onset Sepsis (EOS). The aim of our study was to compare these three recently published recommendations from the COFN for the management of asymptomatic neonates born to afebrile mothers with inadequate IAP for GBS. STUDY DESIGN: This is a retrospective study of asymptomatic neonates with gestational age ≥35 weeks born to afebrile mothers with indicated inadequate IAP for GBS between April 2017 and July 2020. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition. RESULTS: A total of 7,396 infants were born during the study period, 394 (5.3%. to mothers with inadequate IAP. Recommendations for these infants according to both the categorical risk factor guideline and the clinical condition guideline include extended, close observation. However, the SRC recommended routine newborn care for 99.7%.f these infants. None of the infants developed EOS. CONCLUSION: The SRC recommend routine neonatal care without enhanced and prolonged observation for nearly all asymptomatic infants born to afebrile mothers with inadequate IAP. As none of the infants in this cohort had EOS, further studies in a larger cohort are needed to establish the safety of SRC in neonates born to mothers with inadequate IAP.

Community Experience with Pediatric Inspired Treatment of Acute Lymphoblastic Leukemia in the Adolescent and Young Adult Population in Kaiser Permanente Northern and Southern California Regions

Background: Pediatric inspired treatment for Acute Lymphoblastic Leukemia has been increasingly used for treatment of adolescents and young adults in the United States and Europe. In 2019 Dr. Stock published results of CALGB 10403 which showed that a pediatric inspired regimen was tolerable and efficacious in a population of ALL patients up to the age 40. Prior to that publication the use of pediatric inspired treatment was quite variable and mostly used in academic hospital systems. There was concern about tolerability, utilization and efficacy of pediatric inspired protocols. Kaiser Permanente is a vertically integrated care delivery system. The Northern and Southern California regions are the two largest regions each caring for approximately 4.5 million members and cared for in a network of medical offices and hospitals. Methods: We reviewed the Cancer Registries of the Kaiser Permanente Northern and Southern California regions for patients aged 15-39 diagnosed with acute lymphoblastic leukemia between 2010 - 2018. In our patient cohort, 60% of patients were under 26 and 40% were older than 26. We examined the initial induction plan selected and determined if the induction used steroids, vincristine, an anthracycline and asparaginase and if so was classified as pediatric inspired. If not induction was classified as an adult protocol. Patients were characterized as pediatric inspired or adult then followed based on the initial induction plan selected. Neither the sub type of ALL, the molecular characteristics or the MRD status at the end of induction was reviewed. The selection of chemotherapy agents after the initial induction plan was not reviewed. The use of pediatric inspired induction over the time of the study was reviewed. The patients clinical course was reviewed for the next 6 months and utilization including hospital days, ICU days was reviewed. Patients were followed for toxicities of treatments including sepsis, lab abnormalities, and documented side effects of chemotherapy. The pattern of BMT referral was reviewed. The vital status known at the end of the evaluation was also reviewed. Results A total of 222 patients were evaluated. In our patient cohort, 60% of patients were under 26 and 40% were older than 26. Over the study period 66.7 % of the patients received a pediatric inspired induction. The use of pediatric inspired treatments increased over the study period with 38% use in 2010 to 90% in 2018. For patients over age 21 in 2010 the use was 10% in 2018 84%. There was a significantly greater number of inpt days for patients initiated on adult protocols at months, 1, 3 and 6. There was no difference in ICU days. For outpatient utilization there was a significantly higher use of the ED at months 1,3,6 for patients initiated on adult treatments. For patients over 21 there was a significantly increased number of BMT consults during the first 6 months after diagnosis. There was no statistical difference in documented bacteremia, mucositis, pancreatitis, neuropathy or sepsis between the 2 groups. For patients over 26 there was a significant increase in peripheral neuropathy in the adult treated group. There was a significantly elevated risk of mortality at 2 years after diagnosis for the adult treated group. For patients over the age 26 the risk of mortality was similar at 2 years. Conclusion We saw a rapid increase of utilization of pediatric inspired inductions over the study period within the Kaiser Permanente California regions. Patients who initiated treatment on adult protocols had over the first 6 months more inpatient days, were more likely to utilize the ED, were more likely to have a BMT consult. Patients who received adult protocol treatments had higher mortality at 2 years after diagnosis. We conclude that adult oncologists now favor pediatric inspired treatment approaches and there do not seem to be any safety concerns with this approach and in fact pediatric inspired treatments may lead to lower utilization and decreased mortality. Disclosures No relevant conflicts of interest to declare.