Current use of estrogen-containing oral contraceptives or hormone therapy and risk of COVID-19 infection and hospitalization: a population-based cohort study.

This population-based cohort study evaluated the association between current use of oral contraceptives (OC) among women under 50 years (n=306,541), and hormone therapy (HT) among women aged 50 or older (n=323,203), and COVID-19 infection and hospitalization. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified March 2020-February 2021. COVID-19 infection and hospitalization were identified through diagnosis codes and laboratory tests. Weighted generalized estimating equations models estimated multivariable-adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models evaluated OC/HT use and COVID-19 hospitalization. Over 12 months, 11,727 (3.8%) women <50 years and 8,661 (2.7%) women ≥50 years experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR=1.05; 95%CI: 0.97, 1.12). There was a modest association between HT use and infection (aOR=1.19; 95%CI: 1.03, 1.38). Women using OC had a 39% lower risk of hospitalization (aOR=0.61; 95%CI: 0.38, 1.00), but there was no association of HT use with hospitalization (aOR=0.89; 95%CI: 0.51, 1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk.

Pregnancy health in a multi-state U.S. population of systemically underserved patients and their children: PROMISE cohort design and baseline characteristics.

BACKGROUND: Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. METHODS: We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005-2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. RESULTS: The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. CONCLUSIONS: The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

Obesity Disparities Among Adult Single-Race and Multiracial Asian and Pacific Islander Populations.

Importance: Despite increasing numbers of multiracial individuals, they are often excluded in studies or aggregated within larger race and ethnicity groups due to small sample sizes. Objective: To examine disparities in the prevalence of obesity among single-race and multiracial Asian and Pacific Islander individuals compared with non-Hispanic White (hereafter, White) individuals. Design, Setting, and Participants: This cross-sectional study used electronic health record (EHR) data linked to social determinants of health and health behavior data for adult (age ≥18 years) members of 2 large health care systems in California and Hawai'i who had at least 1 ambulatory visit to a primary care practitioner between January 1, 2006, and December 31, 2018. Data were analyzed from October 31, 2022, to July 31, 2023. Exposure: Self-identified race and ethnicity provided in the EHR as a single-race category (Asian Indian, Chinese, Filipino, Japanese, Native Hawaiian only, Other Pacific Islander, or White) or a multiracial category (Asian and Pacific Islander; Asian, Pacific Islander, and White; Asian and White; or Pacific Islander and White). Main Outcomes and Measures: The main outcome was obesity (body mass index [BMI] ≥30.0), based on last measured height and weight from the EHR. Logistic regression was used to examine the association between race and ethnicity and odds of obesity. Results: A total of 5229 individuals (3055 [58.4%] male; mean [SD] age, 70.73 [11.51] years) were examined, of whom 444 (8.5%) were Asian Indian; 1091 (20.9%), Chinese; 483 (9.2%), Filipino; 666 (12.7%), Japanese; 91 (1.7%), Native Hawaiian; 95 (1.8%), Other Pacific Islander; and 888 (17.0%), White. The percentages of individuals who identified as multiracial were as follows: 417 (8.0%) were Asian and Pacific Islander; 392 (7.5%), Asian, Pacific Islander, and White; 248 (4.7%), Asian and White; and 414 (7.9%), Pacific Islander and White. A total of 1333 participants (25.5%) were classified as having obesity based on standard BMI criteria. Obesity was highest among people who identified as Asian, Pacific Islander, and White (204 of 392 [52.0%]) followed by those who identified as Other Pacific Islander (47 of 95 [49.5%]), Native Hawaiian (44 of 91 [48.4%]), and Pacific Islander and White (186 of 414 [44.9%]). After accounting for demographic, socioeconomic, and health behavior factors, people who identified as Asian, Pacific Islander, and White (odds ratio [OR], 1.80; 95% CI, 1.37-2.38) or Pacific Islander and White (OR, 1.55; 95% CI, 1.18-2.04) had increased odds of obesity compared with White individuals. All single-race Asian groups had lower odds of obesity compared with White individuals: Asian Indian (OR, 0.29; 95% CI, 0.20-0.40), Chinese (OR, 0.22; 95% CI, 0.17-0.29), Filipino (OR, 0.46; 95% CI, 0.35-0.62), and Japanese (OR, 0.38, 95% CI, 0.29-0.50). Conclusions and Relevance: In this study, multiracial Asian and Pacific Islander individuals had an increased prevalence of obesity compared with many of their single-race counterparts. As the number of multiracial individuals increases, it will be important for clinical and public health systems to track disparities in these populations.

Mortality in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: We report mortality outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) among people with type 2 diabetes diagnosed within 10 years and no recent history of cardiovascular events or cancer. RESEARCH DESIGN AND METHODS: Overall mortality rates and major causes of death were assessed over an average of 5 years of follow-up. Cause of death was adjudicated centrally by a committee masked to treatment assignment. We examined baseline covariates and the 10-year Framingham Risk Score for associations. RESULTS: Mortality rate was low (0.59 per 100 participant-years). Participants who died during follow-up were likely to be older, be male, have a history of hypertension, have a history of smoking, and have moderate albuminuria. The two most common underlying causes of death were "cardiovascular-cause" (a composite of underlying causes) (38.6%) and cancer (26.8%). There were no differences by treatment group. CONCLUSIONS: Among people with diabetes of relatively short duration, cause of death was varied. Attention to health risks beyond cardiovascular diseases is warranted.

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.

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.

Use of comprehensive recruitment strategies in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE) multi-center clinical trial.

BACKGROUND/AIMS: We present and describe recruitment strategies implemented from 2013 to 2017 across 45 clinical sites in the United States, participating in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, an unmasked, randomized controlled trial evaluating four glucose-lowering medications added to metformin in individuals with type 2 diabetes mellitus (duration of diabetes <10 years). We examined the yield of participants recruited through Electronic Health Records systems compared to traditional recruitment methods to leverage access to type 2 diabetes patients in primary care. METHODS: Site selection criteria included availability of the study population, geographic representation, the ability to recruit and retain a diverse pool of participants including traditionally underrepresented groups, and prior site research experience in diabetes clinical trials. Recruitment initiatives were employed to support and monitor recruitment, such as creation of a Recruitment and Retention Committee, development of criteria for Electronic Health Record systems queries, conduct of remote site visits, development of a public screening website, and other central and local initiatives. Notably, the study supported a dedicated recruitment coordinator at each site to manage local recruitment and facilitate screening of potential participants identified by Electronic Health Record systems. RESULTS: The study achieved the enrollment goal of 5000 participants, meeting its target with Black/African American (20%), Hispanic/Latino (18%), and age ≧60 years (42%) subgroups but not with women (36%). Recruitment required 1 year more than the 3 years originally planned. Sites included academic hospitals, integrated health systems, and Veterans Affairs Medical Centers. Participants were enrolled through Electronic Health Record queries (68%), physician referral (13%), traditional mail outreach (7%), TV, radio, flyers, and Internet (7%), and other strategies (5%). Early implementation of targeted Electronic Health Record queries yielded a greater number of eligible participants compared to other recruitment methods. Efforts over time increasingly emphasized engagement with primary care networks. CONCLUSION: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness successfully recruited a diverse study population with relatively new onset of type 2 diabetes mellitus, relying to a large extent on the use of Electronic Health Record to screen potential participants. A comprehensive approach to recruitment with frequent monitoring was critical to meet the recruitment goal.

Prevalence of cardiovascular disease among Asian, Pacific Islander and multi-race populations in Hawai'i and California.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the US. CVD incidence is influenced by many demographic, clinical, cultural, and psychosocial factors, including race and ethnicity. Despite recent research, there remain limitations on understanding CVD health among Asians and Pacific Islanders (APIs), particularly some subgroups and multi-racial populations. Combining diverse API populations into one study group and difficulties in defining API subpopulations and multi-race individuals have hampered efforts to identify and address health disparities in these growing populations. METHODS: The study cohort was comprised of all adult patients at Kaiser Permanente Hawai'i and Palo Alto Medical Foundation in California during 2014-2018 (n = 684,363). EHR-recorded ICD-9 and ICD-10 diagnosis codes were used to indicate coronary heart disease (CHD), stroke, peripheral vascular disease (PVD), and overall CVD. Self-reported race and ethnicity data were used to construct 12 mutually exclusive single and multi-race groups, and a Non-Hispanic White (NHW) comparison group. Logistic regression models were used to derive prevalence estimates, odds ratios, and confidence intervals for the 12 race/ethnicity groups. RESULTS: The prevalence of CHD and PVD varied 4-fold and stroke and overall CVD prevalence varied 3-fold across API subpopulations. Among Asians, the Filipino subgroup had the highest prevalence of all three CVD conditions and overall CVD. Chinese people had the lowest prevalence of CHD, PVD and overall CVD. In comparison to Native Hawaiians, Other Pacific Islanders had significantly higher prevalence of CHD. For the multi-race groups that included Native Hawaiians and Other Pacific Islanders, the prevalence of overall CVD was significantly higher than that for either single-race Native Hawaiians or Other Pacific Islanders. The multi-race Asian + White group had significantly higher overall CVD prevalence than both the NHW group and the highest Asian subgroup (Filipinos). CONCLUSIONS: Study findings revealed significant differences in overall CVD, CHD, stroke, and PVD among API subgroups. In addition to elevated risk among Filipino, Native Hawaiian, and Other Pacific Islander groups, the study identified particularly elevated risk among multi-race API groups. Differences in disease prevalence are likely mirrored in other cardiometabolic conditions, supporting the need to disaggregate API subgroups in health research.

Association Between Diabetes Severity and Risks of COVID-19 Infection and Outcomes.

BACKGROUND: Little is known about whether diabetes increases the risk of COVID-19 infection and whether measures of diabetes severity are related to COVID-19 outcomes. OBJECTIVE: Investigate diabetes severity measures as potential risk factors for COVID-19 infection and COVID-19 outcomes. DESIGN, PARTICIPANTS, MEASURES: In integrated healthcare systems in Colorado, Oregon, and Washington, we identified a cohort of adults on February 29, 2020 (n = 1,086,918) and conducted follow-up through February 28, 2021. Electronic health data and death certificates were used to identify markers of diabetes severity, covariates, and outcomes. Outcomes were COVID-19 infection (positive nucleic acid antigen test, COVID-19 hospitalization, or COVID-19 death) and severe COVID-19 (invasive mechanical ventilation or COVID-19 death). Individuals with diabetes (n = 142,340) and categories of diabetes severity measures were compared with a referent group with no diabetes (n = 944,578), adjusting for demographic variables, neighborhood deprivation index, body mass index, and comorbidities. RESULTS: Of 30,935 patients with COVID-19 infection, 996 met the criteria for severe COVID-19. Type 1 (odds ratio [OR] 1.41, 95% CI 1.27-1.57) and type 2 diabetes (OR 1.27, 95% CI 1.23-1.31) were associated with increased risk of COVID-19 infection. Insulin treatment was associated with greater COVID-19 infection risk (OR 1.43, 95% CI 1.34-1.52) than treatment with non-insulin drugs (OR 1.26, 95% 1.20-1.33) or no treatment (OR 1.24; 1.18-1.29). The relationship between glycemic control and COVID-19 infection risk was dose-dependent: from an OR of 1.21 (95% CI 1.15-1.26) for hemoglobin A1c (HbA1c) < 7% to an OR of 1.62 (95% CI 1.51-1.75) for HbA1c ≥ 9%. Risk factors for severe COVID-19 were type 1 diabetes (OR 2.87; 95% CI 1.99-4.15), type 2 diabetes (OR 1.80; 95% CI 1.55-2.09), insulin treatment (OR 2.65; 95% CI 2.13-3.28), and HbA1c ≥ 9% (OR 2.61; 95% CI 1.94-3.52). CONCLUSIONS: Diabetes and greater diabetes severity were associated with increased risks of COVID-19 infection and worse COVID-19 outcomes.

Increased COVID-19 Infection Risk Drives Racial and Ethnic Disparities in Severe COVID-19 Outcomes.

COVID-19 inequities have been well-documented. We evaluated whether higher rates of severe COVID-19 in racial and ethnic minority groups were driven by higher infection rates by evaluating if disparities remained when analyses were restricted to people with infection. We conducted a retrospective cohort study of adults insured through Kaiser Permanente (Colorado, Northwest, Washington), follow-up in March-September 2020. Laboratory results and hospitalization diagnosis codes identified individuals with COVID-19. Severe COVID-19 was defined as invasive mechanical ventilation or mortality. Self-reported race and ethnicity, demographics, and medical comorbidities were extracted from health records. Modified Poisson regression estimated adjusted relative risks (aRRs) of severe COVID-19 in full cohort and among individuals with infection. Our cohort included 1,052,774 individuals, representing diverse racial and ethnic minority groups (e.g., 68,887 Asian, 41,243 Black/African American, 93,580 Hispanic or Latino/a individuals). Among 7,399 infections, 442 individuals experienced severe COVID-19. In the full cohort, severe COVID-19 aRRs for Asian, Black/African American, and Hispanic individuals were 2.09 (95% CI: 1.36, 3.21), 2.02 (1.39, 2.93), and 2.09 (1.57, 2.78), respectively, compared to non-Hispanic Whites. In analyses restricted to individuals with COVID-19, all aRRs were near 1, except among Asian Americans (aRR 1.82 [1.23, 2.68]). These results indicate increased incidence of severe COVID-19 among Black/African American and Hispanic individuals is due to higher infection rates, not increased susceptibility to progression. COVID-19 disparities most likely result from social, not biological, factors. Future work should explore reasons for increased severe COVID-19 risk among Asian Americans. Our findings highlight the importance of equity in vaccine distribution.

Adverse Events After Initiating Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Individuals with Heart Failure and Multimorbidity.

BACKGROUND: Current clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events. METHODS: We conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. RESULTS: We identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined. CONCLUSIONS: Routine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure.

Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

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.

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.

Causal evaluation of the health effects of light rail line: A Natural Experiment.

BACKGROUND AND OBJECTIVE: No research to date has causally linked built environment data with health care costs derived from clinically assessed health outcomes within the framework of longitudinal intervention design. This study examined the impact of light rail transit (LRT) line intervention on health care costs after controlling for mode-specific objectively assessed moderateto-vigorous physical activity (MVPA), participant-level neighborhood environmental measures, demographics, attitudinal predispositions, and residential choices. DATA AND METHODS: Based on a natural experiment related to a new LRT line in Portland - 282 individuals divided into treatment and control groups were prospectively followed during the pre- and post-intervention periods. For each individual, we harness high-resolution data on Electronic Medical Record (EMR) based health care costs, mode-specific MVPA, survey-based travel behavior, attitudinal/perception information, and objectively assessed built environment measures. Simulation-assisted longitudinal grouped random parameter models are developed to gain more accurate insights into the effects of LRT line intervention. RESULTS: Regarding the "average effect" of the LRT line intervention, no statistically significant reductions in health care costs were observed for the treated individuals over time. However, substantial heterogeneity was observed not only in the magnitude of effects but its direction as well after controlling for the within- and between-individual variations. For a subgroup of treated individuals, the LRT line opening decreased health care costs over time relative to the control group. Further comparative analysis based on the findings of heterogeneity-based models revealed that the effect of LRT intervention for the treated individuals differed by individual characteristics, attitudes/perceptions, and neighborhood level environmental features. CONCLUSIONS: The study revealed the presence of significant effect modifiers and distinct subgroup structures in the data related to the effects of LRT line intervention on health care costs. Severe implications of ignoring unobserved heterogeneity are highlighted. Limitations and potential avenues for future research are discussed.

Validity of the Exercise Vital Sign Tool to Assess Physical Activity.

INTRODUCTION: Assessment and counseling by healthcare providers can successfully increase physical activity; however, a valid instrument to effectively measure physical activity is needed. This study examines the validity of the Exercise Vital Sign tool by comparing Exercise Vital Sign data collected at Kaiser Permanente Northwest with accelerometry data. METHODS: Participants (n=521) completed accelerometer monitoring and had ≥1 Exercise Vital Sign measurement in their electronic medical record. Using accelerometry as the gold standard, the association between moderate-to-vigorous physical activity minutes per week estimated through Exercise Vital Sign and that estimated through accelerometry was examined using the Spearman correlation coefficient. Comparability of moderate-to-vigorous physical activity categories (inactive, lowly active, moderately active, sufficiently active) was assessed using simple and weighted κ statistics. Sensitivity, specificity, and positive and negative predictive values were calculated. The study was conducted in 2012-2015, with analysis in 2019-2020. RESULTS: Average accelerometry-based moderate-to-vigorous physical activity was 212 minutes per week, and 57% of the participants were considered sufficiently active. Exercise Vital Sign‒based moderate-to-vigorous physical activity averaged 170 minutes per week, and 53% of the participants were active. There was a positive correlation between the moderate-to-vigorous physical activity minutes per week reported through Exercise Vital Sign and that reported through accelerometry (r =0.38, p<0.0001). A fair agreement was observed between Exercise Vital Sign‒ and accelerometry-based moderate-to-vigorous physical activity categories (weighted κ=0.29), with the highest agreement occurring for those with physical activity level ≥150 minutes per week. The positive correlation increased when moderate-to-vigorous physical activity was examined dichotomously (<150 or ≥150 minutes per week, κ=0.34). The sensitivity, specificity, positive predictive value, and negative predictive value for Exercise Vital Sign (when compared with those of accelerometry) were 67%, 68%, 61%, and 73%, respectively. CONCLUSIONS: The Exercise Vital Sign is a useful physical activity assessment tool that correctly identifies the majority of adults who do and do not meet physical activity guidelines.

Evaluating the Implementation of Digital and In-Person Diabetes Prevention Program in a Large, Integrated Health System: Natural Experiment Study Design.

INTRODUCTION: Implementation of a Diabetes Prevention Program (DPP) in both in-person and digital health-care settings has been increasing. The purpose of this article is to describe the protocol of a mixed-methods, natural experiment study designed to evaluate the implementation of DPP in a large, integrated health system. METHODS: Kaiser Permanente Northwest patients who were 19 to 75 years with prediabetes (hemoglobin A1c or glycated hemoglobin, 5.7-6.4) and obesity (body mass index ≥ 30 kg/m2) were invited, via the Kaiser Permanente Northwest patient portal, to participate in the digital (n = 4124) and in-person (n = 2669) DPP during 2016 through 2018. Primary (weight) and secondary (hemoglobin A1c or glycated hemoglobin level) outcome data will be obtained from electronic health records. A cost-effectiveness analysis as well as qualitative interviews with patients (enrolled and not enrolled in the DPP) and stakeholders will be conducted to examine further implementation, acceptability, and sustainability. CONCLUSION: The mixed-methods, natural experiment design we will use to evaluate Kaiser Permanente Northwest's implementation of the digital and in-person DPP builds on existing evidence related to the effectiveness of these two DPP delivery modes and will contribute new knowledge related to best practices for implementing and sustaining the DPP within large health systems over the long term.

Primary Prevention Trial Designs Using Coronary Imaging: A National Heart, Lung, and Blood Institute Workshop.

Coronary artery calcium (CAC) is considered a useful test for enhancing risk assessment in the primary prevention setting. Clinical trials are under consideration. The National Heart, Lung, and Blood Institute convened a multidisciplinary working group on August 26 to 27, 2019, in Bethesda, Maryland, to review available evidence and consider the appropriateness of conducting further research on coronary artery calcium (CAC) testing, or other coronary imaging studies, as a way of informing decisions for primary preventive treatments for cardiovascular disease. The working group concluded that additional evidence to support current guideline recommendations for use of CAC in middle-age adults is very likely to come from currently ongoing trials in that age group, and a new trial is not likely to be timely or cost effective. The current trials will not, however, address the role of CAC testing in younger adults or older adults, who are also not addressed in existing guidelines, nor will existing trials address the potential benefit of an opportunistic screening strategy made feasible by the application of artificial intelligence. Innovative trial designs for testing the value of CAC across the lifespan were strongly considered and represent important opportunities for additional research, particularly those that leverage existing trials or other real-world data streams including clinical computed tomography scans. Sex and racial/ethnic disparities in cardiovascular disease morbidity and mortality, and inclusion of diverse participants in future CAC trials, particularly those based in the United States, would enhance the potential impact of these studies.

Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight.

OBJECTIVE: We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for <10 years and an HbA1c ≥6.8% (51 mmol/mol) while taking ≥500 mg of metformin/day. Participants also received diet and exercise counseling. The primary outcome was the change in HbA1c during run-in. RESULTS: Adjusted for duration of run-in, the mean ± SD change in HbA1c was -0.65 ± 0.02% (-7.1 ± 0.2 mmol/mol) when the dose was increased by ≥1,000 mg/day, -0.48 ± 0.02% (-5.2 ± 0.2 mmol/mol) when the dose was unchanged, and -0.23 ± 0.07% (-2.5 ± 0.8 mmol/mol) when the dose was decreased (n = 2,169, 3,548, and 192, respectively). Higher HbA1c at entry predicted greater reduction in HbA1c (P < 0.001) in univariate and multivariate analyses. Weight loss adjusted for duration of run-in averaged 0.91 ± 0.05 kg in participants who increased metformin by ≥1,000 mg/day (n = 1,894). CONCLUSIONS: Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes and HbA1c values ≥6.8% (51 mmol/mol). These findings may help guide efforts to optimize metformin therapy among persons with type 2 diabetes and suboptimal glycemic control.