Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection in Children and Adolescents Aged 5 to 17 Years.

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Abnormal uterine bleeding diagnoses and care following COVID-19 vaccination.

BACKGROUND: There is evidence suggesting that COVID-19 vaccination may be associated with small, transitory effects on uterine bleeding, possibly including menstrual timing, flow, and duration, in some individuals. However, changes in health care seeking, diagnosis, and workup for abnormal uterine bleeding in the COVID-19 vaccine era are less clear. OBJECTIVE: This study aimed to assess the impact of COVID-19 vaccination on incident abnormal uterine bleeding diagnosis and diagnostic evaluation in a large integrated health system. STUDY DESIGN: Using segmented regression, we assessed whether the availability of COVID-19 vaccines was associated with changes in monthly, population-based rates of incident abnormal uterine bleeding diagnoses relative to the prepandemic period in health system members aged 16 to 44 years who were not menopausal. We also compared clinical and demographic characteristics of patients diagnosed with incident abnormal uterine bleeding between December 2020 and October 13, 2021 by vaccination status (never vaccinated, vaccinated in the 60 days before diagnosis, vaccinated >60 days before diagnosis). Furthermore, we conducted detailed chart review of patients diagnosed with abnormal uterine bleeding within 1 to 60 days of COVID-19 vaccination in the same time period. RESULTS: In monthly populations ranging from 79,000 to 85,000 female health system members, incidence of abnormal uterine bleeding diagnosis per 100,000 person-days ranged from 8.97 to 19.19. There was no significant change in the level or trend in the incidence of abnormal uterine bleeding diagnoses between the prepandemic (January 2019-January 2020) and post-COVID-19 vaccine (December 2020-December 2021) periods. A comparison of clinical characteristics of 2717 abnormal uterine bleeding cases by vaccination status suggested that abnormal bleeding among recently vaccinated patients was similar or less severe than abnormal bleeding among patients who had never been vaccinated or those vaccinated >60 days before. There were also significant differences in age and race of patients with incident abnormal uterine bleeding diagnoses by vaccination status (Ps<.02). Never-vaccinated patients were the youngest and those vaccinated >60 days before were the oldest. The proportion of patients who were Black/African American was highest among never-vaccinated patients, and the proportion of Asian patients was higher among vaccinated patients. Chart review of 114 confirmed postvaccination abnormal uterine bleeding cases diagnosed from December 2020 through October 13, 2021 found that the most common symptoms reported were changes in timing, duration, and volume of bleeding. Approximately one-third of cases received no diagnostic workup; 57% had no etiology for the bleeding documented in the electronic health record. In 12% of cases, the patient mentioned or asked about a possible link between their bleeding and their recent COVID-19 vaccine. CONCLUSION: The availability of COVID-19 vaccination was not associated with a change in incidence of medically attended abnormal uterine bleeding in our population of over 79,000 female patients of reproductive age. In addition, among 2717 patients with abnormal uterine bleeding diagnoses in the period following COVID-19 vaccine availability, receipt of the vaccine was not associated with greater bleeding severity.

Training Health Center Staff in the Provision of Culturally Responsive Care for Sexual and Gender Minority Patients: Results of a Randomized Controlled Trial.

Purpose: The study was designed to evaluate whether an educational intervention to train the health center (HC) staff to optimize care for sexual and gender minority (SGM) patients could improve documentation of sexual orientation and gender identity (SOGI) and increase preventive screenings. Methods: Twelve HCs were matched and randomized to either receive a tailored, multicomponent educational intervention or a 1-hour prerecorded webinar. Documentation of SGM status and clinical testing was measured through analysis of data that HCs report annually. Nonparametric statistics were used to assess associations between baseline HC characteristics and outcome measures. Results: The HCs were geographically, racially, and ethnically diverse. In all but one HC, <10% of the patients were identified as SGM. Intervention HCs underwent between 3 and 10 trainings, which were highly acceptable. In 2018, 9 of 12 HCs documented SO and 11 of 12 documented GI for at least 50% of their patients. Five of 6 intervention HCs increased SO documentation by 2020, compared to 3 of 6 control HCs (nonsignificant, NS). Five intervention HCs increased GI documentation, although generally by less than 10%, compared to 2 of the controls (NS). Intervention HCs tended to increase documentation of preventive services more than control HCs, but the changes were NS. Conclusions: An educational intervention designed to train the HC staff to provide culturally responsive services for SGM patients was found to be acceptable, with favorable, but nonsignificant changes. Further refinement of the intervention using a larger sample of HCs might demonstrate the effectiveness of this approach. Clinical trial registration #: NCT03554785.

Postmenopausal bleeding after COVID-19 vaccination.

BACKGROUND: There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination. OBJECTIVE: This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination. STUDY DESIGN: For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology. RESULTS: In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination. CONCLUSION: Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.

Sleep Characteristics are Associated with Risk of Treated Diabetes Among Postmenopausal Women.

OBJECTIVE: The purpose of this study was to determine whether sleep characteristics are associated with incidence of treated diabetes in postmenopausal individuals. METHODS: Postmenopausal participants ages 50-79 years reported sleep duration, sleep-disordered breathing, or insomnia at baseline and again in a subsample 3 years later. The primary outcome was self-reported new diagnosis of diabetes treated with oral drugs or insulin at any time after baseline. Multivariable Cox proportional hazards models were used. RESULTS: In 135,964 participants followed for 18.1 (± 6.3) years, there was a nonlinear association between sleep duration and risk of treated diabetes. Participants sleeping ≤5 hours at baseline had a 21% increased risk of diabetes compared with those sleeping 7 hours (adjusted hazard ratio [aHR] 1.21; 95% confidence interval [CI], 1.00-1.47). Those who slept for ≥9 hours had a nonsignificant 6% increased risk of diabetes compared with those sleeping 7 hours (aHR 1.06; 95% CI, 0.97-1.16). Participants whose sleep duration had decreased at 3 years had a 9% (aHR 1.09; 95% CI, 1.02-1.16) higher risk of diabetes than participants with unchanged sleep duration. Participants who reported increased sleep duration at 3 years had a risk of diabetes (HR 1.01; 95% CI, 0.95-1.08) similar to those with no sleep duration change. Participants at high risk of sleep-disordered breathing at baseline had a 31% higher risk of diabetes than those without (aHR 1.31; 95% CI, 1.26-1.37). No association was found between self-reported insomnia score and diabetes risk. CONCLUSIONS: Sleep-disordered breathing and short or long sleep duration were associated with higher diabetes risk in a postmenopausal population.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink.

BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree."

Mental health diagnosis attenuates weight loss among older adults in a digital diabetes prevention program.

Objective: Diabetes Prevention Programs (DPP) are effective at reducing diabetes incidence via clinically significant weight loss. Co-morbid mental health condition(s) may reduce the effect of DPP administered in-person and telephonically but this has not been assessed for digital DPP. This report examines the moderating effect of mental health diagnosis on weight change among individuals who enrolled in digital DPP (enrollees) at 12 and 24 months. Methods: Secondary analysis of prospective, electronic health record data from a study of digital DPP among adults (N = 3904) aged 65-75 with prediabetes (HbA1c 5.7%-6.4%) and obesity (BMI ≥30 kg/m2). Results: Mental health diagnosis only moderated the effect of digital DPP on weight change during the first 7 months (p = 0.003) and the effect attenuated at 12 and 24 months. Results were unchanged after adjusting for psychotropic medication use. Among those without a mental health diagnosis, digital DPP enrollees lost more weight than non-enrollees: -4.17 kg (95% CI, -5.22 to -3.13) at 12 months and -1.88 kg (95% CI, -3.00 to -0.76) at 24 months, whereas among individuals with a mental health diagnosis, there was no difference in weight loss between enrollees and non-enrollees at 12 and 24 months (-1.25 kg [95% CI, -2.77 to 0.26] and 0.02 kg [95% CI, -1.69-1.73], respectively). Conclusions: Digital DPP appears less effective for weight loss among individuals with a mental health condition, similar to prior findings for in-person and telephonic modalities. Findings suggest a need for tailoring DPP to address mental health conditions.

Care trajectories for patients utilizing electronic visits for COVID-like symptoms in a large healthcare delivery system: May 2020-December 2021.

BACKGROUND: There is limited information about how on-line screening tools developed by integrated systems facilitated management of COVID-like illness patients. METHODS: Using the Kaiser Permanente Northwest (KPNW) Electronic Health Record, we identified adult plan members who accessed online COVID-19 screening e-visits and enumerated their subsequent medical encounters, tests for SARS-CoV-2, and test outcomes. RESULTS: Between May 2020 and December 2021, members completed 55,139 e-visits, with disproportionate representation among females (65% vs. 53% in the overall membership) and members aged <45 years (61% vs. 39%). Thirty percent of patients (16,953) were managed entirely through e-visits and 70% received subsequent in-person care. The percent of SARS-CoV-2 positive individuals was highest among the 1055 individuals triaged to inpatient care (17.9%), compared to 9.5% among those escalated to additional ambulatory care. CONCLUSIONS: The e-visit on-line screening tool helped KPNW assist thousands of patients with COVID-19 symptoms, avoid unnecessary in-person patient encounters, and preserved KPNW infection control and pandemic surge capacity.

Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink.

BACKGROUND: The Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study's objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. METHODS: VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. RESULTS: More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. CONCLUSIONS: In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.

A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink.

BACKGROUND: Except for spontaneous reporting systems, vaccine safety monitoring generally involves pre-specifying health outcomes and post-vaccination risk windows of concern. Instead, we used tree-based data-mining to look more broadly for possible adverse events after Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees receiving ≥1 dose of COVID-19 vaccine in 2020-2021 were followed for 70 days after Pfizer-BioNTech or Moderna and 56 days after Janssen vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the post-vaccination follow-up period. We used the self-controlled tree-temporal scan statistic and TreeScan software. Monte Carlo simulation was used to estimate p-values; p = 0.01 was the pre-specified cut-off for statistical significance of a cluster. RESULTS: There were 4.1, 2.6, and 0.4 million Pfizer-BioNTech, Moderna, and Janssen vaccinees, respectively. Clusters after Pfizer-BioNTech vaccination included: (1) unspecified adverse effects, (2) common vaccine reactions, such as fever, myalgia, and headache, (3) myocarditis/pericarditis, and (4) less specific cardiac or respiratory symptoms, all with the strongest clusters generally after Dose 2; and (5) COVID-19/viral pneumonia/sepsis/respiratory failure in the first 3 weeks after Dose 1. Moderna results were similar but without a significant myocarditis/pericarditis cluster. Further investigation suggested the fifth signal group was a manifestation of mRNA vaccine effectiveness after the first 3 weeks. Janssen vaccinees had clusters of unspecified or common vaccine reactions, gait/mobility abnormalities, and muscle weakness. The latter two were deemed to have arisen from confounding related to practices at one site. CONCLUSIONS: We detected post-vaccination clusters of unspecified adverse effects, common vaccine reactions, and, for the mRNA vaccines, chest pain and palpitations, as well as myocarditis/pericarditis after Pfizer-BioNTech Dose 2. Unique advantages of this data mining are its untargeted nature and its inherent adjustment for the multiplicity of diagnoses and risk intervals scanned.

Prepare randomized clinical trial: Acceptability, engagement, and lifestyle effects of a weight loss intervention beginning in pre-pregnancy.

Background: Healthier lifestyles in early pregnancy are associated with lower rates of pregnancy complications, childhood adiposity, and maternal and child cardiovascular risks. However, it is not known whether lifestyle coaching initiated prior to pregnancy can affect behavior and attitudes during pregnancy. Methods: Three hundred and twenty six women planning pregnancy within 2 years with BMI ≥27 kg/m2 were randomized to a behavioral weight loss intervention or to usual care. Analyses reported here examined the intervention's impact on mid-pregnancy diet quality and activity levels; program acceptability; and effects of pregnancy on intervention engagement. Results: One hundred and sixty eight participants experienced pregnancy during the study (intervention: 91; usual care: 77). From randomization to mid-pregnancy, participants who received the intervention had larger increases in fruit intake than usual care participants (+0.67 vs. +0.06 cups; p = 0.02) and engaged in more vigorous-intensity activity (3.9 [5.5] vs. 1.2 [3.0] Met-hr/week p = 0.002) and sports/exercise (17.0 [14.1] vs. 11.0 [9.5] Met-hr/week; p = 0.03); the groups also differed in changes in sedentary time (-4.9 [15.0] vs. +0.5 [7.6] Met-hr/week; p = 0.02). Intervention satisfaction was high (>80%), and experiencing pregnancy during the intervention was associated with higher engagement. Conclusion: A coaching-based intervention beginning in pre-pregnancy successfully helped women attain healthier diet and exercise habits in mid-pregnancy. Clinical trials registration: Registered with ClinicalTrials.gov, NCT02346162, first registered on January 26, 2015, before date of initial participant enrollment (May 2015), https://clinicaltrials.gov/ct2/show/NCT02346162.

Evaluating the Implementation of a Digital Diabetes Prevention Program in an Integrated Health Care Delivery System Among Older Adults: Results of a Natural Experiment.

The purpose of this natural experiment study was to assess the effectiveness of a 12-month digital Diabetes Prevention Program (DPP) for adults aged 65-75 years with prediabetes and obesity within a large, integrated health care system. Adjusting for propensity scores and covariates, patients who enrolled and participated in the digital DPP had a mean weight loss of 8.6 lb over 12 months and 5.7 lb by 24 months, compared with a steady, minimal weight loss of 1.3 lb over 12 months and 2.8 lb by 24 months among patients not enrolled. There was a significant difference in mean change in A1C between enrolled and nonenrolled patients over 12 months (-0.10%), but not by 24 months (-0.06%). Digital DPP appears to be an effective weight loss option and potential diabetes prevention intervention for older adults at high risk for type 2 diabetes.

Costs and Cost-Effectiveness of Implementing a Digital Diabetes Prevention Program in a Large, Integrated Health System.

BackgroundThe Diabetes Prevention Program (DPP) has been translated into digital formats. We report an economic evaluation of a digital DPP implemented in a large, integrated health care system. MethodsPatients (n = 4148) were invited to participate in digital DPP based on clinical characteristics (HbA1c 5.7%-6.4% and body mass index ≥ 30 kg/m2) assessed using electronic medical record data. Using a propensity score we matched (1:1) enrolled and not enrolled patients for a total of 784. We identified high-risk patients (ie, above the 50th percentile of risk; n = 202) by calculating each patient's 2-year of developing diabetes. We report the cost of the intervention and the costs of medical care over 12- and 24-month follow-up, and the incremental cost-effectiveness ratio as the cost per additional kilogram weight loss at 24 months. ResultsAt 12 months, enrolled patients had lower total costs ($6,926, 95% CI $5,681-$8,171) than not enrolled patients ($7,538, 95% CI $6,293-$8,783). This pattern attenuated slightly at 24 months (enrolled = $16,255, 95% CI $14,097-$18,412; not enrolled = $16,688, 95% CI $14,531-$18,846). We found an incremental cost-effectiveness ratio of $81.92 per additional kilogram weight loss. For high-risk patients, the digital DPP group had, on average, lower costs and greater weight loss. We found a 55% chance of the digital DPP program being cost-effective at a willingness-to-pay of $150 per additional kilogram of weight loss; at the same willingness-to-pay, there is a 60% chance in the high-risk subgroup. Limitations include the nonrandomized design and potential volunteer bias. ConclusionDigital DPP had a favorable cost-effectiveness profile compared to other lifestyle interventions.

Bridge to Health/Puente a la Salud: a pilot randomized trial to address diabetes self-management and social needs among high-risk patients.

Social needs contribute to persistent diabetes disparities; thus, it is imperative to address social needs to optimize diabetes management. The purpose of this study was to determine determine the feasibility and acceptability of health system-based social care versus social care + behavioral intervention to address social needs and improve diabetes self-management among patients with type 2 diabetes. Black/African American, Hispanic/Latino, and low-income White patients with recent hemoglobin A1C (A1C) ≥ 8%, and ≥1 social need were recruited from an integrated health system. Patients were randomized to one-of-two 6-month interventions: (a) navigation to resources (NAV) facilitated by a Patient Navigator; or (b) NAV + evidence-based nine-session diabetes self-management support (DSMS) program facilitated by a community health worker (CHW). A1C was extracted from the electronic health record. We successfully recruited 110 eligible patients (54 NAV; 56 NAV + DSMS). During the trial, 78% NAV and 80% NAV + DSMS participants successfully connected to a navigator; 84% NAV + DSMS connected to a CHW. At 6-month follow-up, 33% of NAV and 34% of NAV + DSMS participants had an A1C < 8%. Mean reduction in A1C was clinically significant in NAV (-0.65%) and NAV + DSMS (-0.72%). By follow-up, 89% of NAV and 87% of NAV + DSMS were successfully connected to resources to address at least one need. Findings suggest that it is feasible to implement a health system-based social care intervention, separately or in combination, with a behavioral intervention to improve diabetes management among a high-risk, socially complex patient population. A larger, pragmatic trial is needed to test the comparative effectiveness of each approach on diabetes-related outcomes.

Wide Variability in Documentation of Sexual Orientation, Gender Identity, and Preventive Health Screenings in a Diverse Sample of U.S. Community Health Centers.

Purpose: This study was conducted to characterize documentation of sexual orientation and gender identity (SOGI) and provision of screening and preventive services in a diverse sample of community health centers (CHCs). Methods: Twelve CHCs provided data submitted to the Health Resources and Services Administration (HRSA) in 2018 from their Uniform Data System (UDS) reports. Prevalence of SOGI documentation, screenings, and preventive services were calculated. Sociodemographic correlates of documentation were analyzed using Fisher's exact test and Wilcoxon rank sum/Mann-Whitney U test. Results: Patient data recording sexual orientation (SO) were missing in 2%-93% of UDS reports from the 12 CHCs, and gender identity (GI) data were missing from 0% to 96% of UDS reports. CHCs were most likely to report body mass index and tobacco screening and least likely to report hepatitis A or B vaccination, independent of SO or GI. Transgender females were less likely to have mammography documented than cisgender females. Transgender males were less likely to have anal Pap tests, be vaccinated for hepatitis B, or be referred for risky alcohol use compared to cisgender males. Patients who identified as "another gender" were less likely to be referred for risky alcohol use, undergo mammography or anal Pap testing, or receive hepatitis A vaccination than cisgender people. Individuals who did not disclose their GI were less likely to be vaccinated for hepatitis A or B than cisgender people. Conclusion: SOGI status was often not documented by a diverse array of CHCs. However, when SOGI status was documented, we saw evidence of disparities in preventive interventions and referrals, particularly for transgender patients. Clinical trial registration number: NCT03554785.

Incidence of SARS-CoV-2 Infection, Emergency Department Visits, and Hospitalizations Because of COVID-19 Among Persons Aged ≥12 Years, by COVID-19 Vaccination Status - Oregon and Washington, July 4-September 25, 2021.

Population-based rates of infection with SARS-CoV-2 (the virus that causes COVID-19) and related health care utilization help determine estimates of COVID-19 vaccine effectiveness and averted illnesses, especially since the SARS-CoV-2 B.1.617.2 (Delta) variant began circulating in June 2021. Among members aged ≥12 years of a large integrated health care delivery system in Oregon and Washington, incidence of laboratory-confirmed SARS-CoV-2 infection, emergency department (ED) visits, and hospitalizations were calculated by COVID-19 vaccination status, vaccine product, age, race, and ethnicity. Infection after full vaccination was defined as a positive SARS-CoV-2 molecular test result ≥14 days after completion of an authorized COVID-19 vaccination series.* During the July-September 2021 surveillance period, SARS-CoV-2 infection occurred among 4,146 of 137,616 unvaccinated persons (30.1 per 1,000 persons) and 3,009 of 344,848 fully vaccinated persons (8.7 per 1,000). Incidence was higher among unvaccinated persons than among vaccinated persons across all demographic strata. Unvaccinated persons with SARS-CoV-2 infection were more than twice as likely to receive ED care (18.5%) or to be hospitalized (9.0%) than were vaccinated persons with COVID-19 (8.1% and 3.9%, respectively). The crude mortality rate was also higher among unvaccinated patients (0.43 per 1,000) than in fully vaccinated patients (0.06 per 1,000). These data support CDC recommendations for COVID-19 vaccination, including additional and booster doses, to protect individual persons and communities against COVID-19, including illness and hospitalization caused by the Delta variant (1).

Weight Loss Prior to Pregnancy and Early Gestational Glycemia: Prepare, a Randomized Clinical Trial.

CONTEXT: Women with elevated body mass index are encouraged to lose weight before pregnancy, but no trials have tested the effects of prepregnancy weight loss on risk of developing gestational diabetes. OBJECTIVE: This work aims to determine whether prepregnancy weight loss improved the early metabolic environment as measured by early gestational diabetes diagnosis. METHODS: This was a secondary analysis of a pragmatic randomized clinical trial conducted between May 2015 and October 2019 in an integrated health system that encouraged first-trimester gestational diabetes screening for high-risk women, including those with obesity. Women aged 18 to 40 years with a body mass index (BMI) greater than or equal to 27 who were planning pregnancy were randomly assigned to a behavioral weight loss intervention or usual care. Clinical care decisions and data collection were blind to condition assignment. We compared rates of diagnosis with gestational diabetes in early pregnancy between the groups using logistic regression. RESULTS: Of 326 participants, 168 (89 in the intervention and 79 in usual care) had singleton pregnancies during the study period. At baseline, mean age was 31.3 ±â€…3.5 years and BMI was 34.8 ±â€…5.8. Fifty-nine (66%) intervention participants and 57 (72%) usual care participants underwent early screening. Among those, intervention participants were 73% less likely to be diagnosed with gestational diabetes than usual care participants (adjusted odds ratio [aOR], 0.27; 95% CI, 0.09-0.80). There was no difference in diagnosis of gestational diabetes in later pregnancy (aOR, 1.08; 95% CI, 0.41-2.81). CONCLUSION: Participation in a prepregnancy weight loss intervention led to lower rates of gestational diabetes diagnosis in early pregnancy. This suggests positive effects of prepregnancy weight loss on the early metabolic environment, a critical factor in offspring metabolic risk.

Bridge to Health/ Puente a la Salud: Rationale and design of a pilot feasibility randomized trial to address diabetes self-management and unmet basic needs among racial/ethnic minority and low-income patients.

INTRODUCTION: Racial/ethnic and socioeconomic disparities in diabetes prevalence and management persist. Unmet basic needs such as food insecurity and unstable housing interfere with optimal diabetes self-management. Bridge to Health/Puente a la Salud is a randomized pilot trial designed to examine the feasibility of testing the effectiveness of addressing unmet basic needs via navigation services versus navigation plus diabetes self-management support (DSMS) on improving diabetes-related outcomes among racial/ethnic minority and low-income patients with uncontrolled diabetes. MATERIAL AND METHODS: We recruited and randomized 110 African American, Hispanic, and Medicaid patients (any race/ethnicity) with diabetes and recent hemoglobin A1C ≥ 8% to one of two 6-month interventions: 1) Navigation only; or 2) Navigation + DSMS. In both arms, practice-embedded patient navigators help participants navigate social services and community-based resources to address unmet basic needs. In Navigation + DSMS, participants are also assigned to a community health worker (CHW) embedded in a local community-based organization who provides additional navigation support and delivers DSMS. A1C and unmet basic needs data are collected via routine lab and survey, respectively, at baseline and 6-month follow-up. Qualitative interviews with participants, health system leaders, CHWs, and patient navigators are conducted to explore intervention acceptability and determinants of implementation in a health care setting. DISCUSSION: Findings from this pilot feasibility study will enhance understanding about acceptability, preliminary clinical effectiveness, and facilitators and barriers to implementation of the Navigation only and Navigation + DSMS interventions and inform refinements of the overall study design for the larger, randomized clinical trial.