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Objective: To examine short-term mortality and cause of death among youth and young adults (YYAs) with youth-onset diabetes.Research Design and Methods: We included 19,717 YYAs newly diagnosed with diabetes before 20 years of age from 1 January 2002 to 31 December 2015 enrolled in the SEARCH for Diabetes in Youth Study. Of these, 14,721 had type 1; 4,141 type 2; and 551 secondary and 304 other/unknown diabetes type. Cases were linked with the National Death Index through 31 December 2017. We calculated standardized mortality ratios (SMRs) and 95% CIs based on age, sex, and race/ethnicity for state and county population areas and examined underlying causes of death.Results: During 170,148 person-years (PY) (median follow-up 8.5 years), 283 individuals died: 133 with type 1 (103.0/100,000 PY), 55 with type 2 (161.5/100,000 PY), 87 with secondary (1,952/100,000 PY), and 8 with other/unknown diabetes type (312.3/100,000 PY). SMRs (95% CI) for the first three groups were 1.5 (1.2-1.8), 2.3 (1.7-3.0), and 28.0 (22.4-34.6), respectively. Diabetes was the underlying cause of death for 42.1%, 9.1%, and 4.6% of deaths, respectively. The SMR was greater for type 2 than for type 1 diabetes (P < 0.001). SMRs were significantly higher for individuals with type 1 diabetes who were <20 years of age, non-Hispanic White and Hispanic, and female and for individuals with type 2 diabetes who were <25 years of age, from all race/ethnic minority groups, and from both sexes.Conclusions: Excess mortality was observed among YYAs for each type of diabetes with differences in risk associated with diabetes type, age, race/ethnicity, and sex. The root causes of excess mortality among YYAs with diabetes merit further study. [ABSTRACT FROM AUTHOR]

Background: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking.Research Question: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19?Study Design and Methods: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between February 2020 and August 2020 from two integrated health-care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19.Results: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL.Interpretation: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19. [ABSTRACT FROM AUTHOR]

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% (n = 3442) with CLI and 68.9% (n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% (n = 4481) who were not on a statin in the year before diagnosis, 13.5% (n = 607) newly initiated therapy within 1 month (CLI: 10.1% (n = 150); without CLI: 15.3% (n = 457)). Following diagnosis, 12.5% (n = 660) discontinued statin therapy within 1 year (CLI: 15.5% (n = 202); without CLI: 11.5% (n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes. [ABSTRACT FROM AUTHOR]

Aims: To estimate short-term mortality rates for individuals with type 1 or type 2 diabetes diagnosed before age 20 years from the SEARCH for Diabetes in Youth study.Methods: We included 8358 individuals newly-diagnosed with type 1 (n = 6840) or type 2 (n = 1518) diabetes from 1/1/2002-12/31/2008. We searched the National Death Index through 12/31/2010. We calculated standardized mortality ratios (SMRs) based on age, sex, and race for the comparable US population in the geographic areas of the SEARCH study.Results: During 44,893 person-years (PY) of observation (median follow-up = 5.3 years), 41 individuals died (91.3 deaths/100,000 PY); 26 with type 1 (70.6 deaths/100,000 PY) and 15 with type 2 (185.6 deaths/100,000 PY) diabetes. The expected mortality rate was 70.9 deaths/100,000 PY. The overall SMR (95% CI) was 1.3 (1.0, 1.8) and was high among individuals with type 2 diabetes 2.4 (1.3, 3.9), females 2.2 (1.3, 3.3), 15-19 year olds 2.7 (1.7,4.0), and non-Hispanic blacks 2.1 (1.2, 3.4).Conclusions: Compared to the state populations of similar age, sex, and race, our results show excess mortality in individuals with type 2 diabetes, females, older youth, and non-Hispanic blacks. We did not observe excess short-term mortality in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations.Methods: We examined trends in hospitalized acute myocardial infarction incidence among adults aged ≥25 years in 13 US health plans in the Cardiovascular Research Network. The first hospitalization per member for acute myocardial infarction overall and for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge codes in each calendar year from 2000 through 2008. Age- and sex-adjusted incidence was calculated per 100,000 person-years using direct adjustment with 2000 US census data.Results: Between 2000 and 2008, we identified 125,435 acute myocardial infarction hospitalizations. Age- and sex-adjusted incidence rates (per 100,000 person-years) of acute myocardial infarction decreased an average 3.8%/y from 230.5 in 2000 to 168.6 in 2008. Incidence of ST-segment elevation myocardial infarction decreased 8.7%/y from 104.3 in 2000 to 51.7 in 2008, whereas incidence of non-ST-segment elevation myocardial infarction increased from 126.1 to 129.4 between 2000 and 2004 and then decreased thereafter to 116.8 in 2008. Age- and sex-specific incidence rates generally reflected similar patterns, with relatively larger decreases in ST-segment elevation myocardial infarction rates in women compared with men. As compared with 2000, the age-adjusted incidence of ST-segment elevation myocardial infarction in 2008 was 48% lower among men and 61% lower among women.Conclusions and Relevance: Among a large, diverse, multicenter community-based insured population, there were significant decreases in incidence of hospitalized acute myocardial infarction and the more serious ST-segment elevation myocardial infarctions between 2000 and 2008. Decreases in ST-segment elevation myocardial infarctions were most pronounced among women. While ecologic in nature, these secular decreases likely reflect, at least in part, results of improvement in primary prevention efforts. [ABSTRACT FROM AUTHOR]

Aims: To investigate the discontinuation of oral antihyperglycemic agents (OHA), and examine factors associated with OHA discontinuation, and the effect of OHA discontinuation on glycemic control and healthcare utilization among diabetes patients prescribed dual OHA therapy.Methods: We identified 23,612 adult patients aged >18years with a diagnosis of type 2 diabetes who initiated dual OHA therapy between 1/1/2005 and 6/30/2010. The date of initiation of the second OHA was defined as the index date. Discontinuation was defined as a gap >1.5 times the last days' supply without subsequent reinitiation.Results: Over 24months, 16.9% discontinued 1 OHA and 9.2% discontinued both. Patients who discontinued were more likely to be female, younger, Black or of Hispanic ethnicity, have more comorbidities, higher medication co-pays, start both OHAs together, have higher healthcare utilization before the index date and less likely to use prescription mail order compared with patients who did not discontinue. In multivariable regression models, patients who discontinued were more likely to be hospitalized or have emergency department visits during follow-up.Conclusions: Discontinuation of OHAs is common among patients with diabetes and is associated with several patient factors and increased healthcare utilization. Future research should further examine reasons for OHA discontinuation. [ABSTRACT FROM AUTHOR]

Because heart failure (HF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) are different clinical entities with differing demographic characteristics, common HF outcomes may occur at different rates. Comparative outcome studies have been equivocal, and studies comparing resource utilization are scant. We used an observational cohort design to study 6,513 patients hospitalized for HF who had an EF measured during the hospitalization and were discharged alive within 30 days. We excluded 677 patients with borderline EF values (41% to 49%) and categorized the remaining as HFrEF (EF ≤40%, n = 2,205) and HFpEF (EF >50%, n = 3,631). Patients were followed for up to 1 year for all-cause re-hospitalization and mortality and annualized medical resource utilization. Patients with HFrEF and HFpEF experienced similar adjusted incidence rates of re-hospitalization, but those with HFrEF had a 39% increased risk of mortality at 30 days (rate ratio 1.39, 95% confidence interval 1.10 to 1.76) and 25% greater risk at 1 year (rate ratio1.25, 95% confidence interval 1.12 to 1.41). After adjustment for covariates, patients with HFpEF incurred significantly more annualized outpatient visits (21.5 vs 20.1, p = 0.002) and emergency room visits (3.24 vs 2.94, p = 0.002) than those with HFrEF, but absolute differences were small. High inpatient and pharmacy utilization did not differ. Our study suggests that whether a patient has HFrEF or HFpEF has little bearing on risk of re-hospitalization or inpatient resource utilization in the year after an HF hospitalization. Both groups experienced high mortality, but those with HFrEF had greater risk. In conclusion, from the standpoint of resource use, HF can be considered a single entity. [ABSTRACT FROM AUTHOR]

Heart failure (HF) hospitalization length of stay (LOS) has been associated with the risk of subsequent readmission and mortality. We identified 19,927 hospitalized patients with HF who were discharged alive from 2008 to 2011 from 3 Kaiser Permanente regions. In adjusted Cox models using LOS 3 to 4 days as the reference category, shorter LOS was not significantly associated with hospital readmissions. LOS of 5 to 10 days was associated with 17% greater risk of readmission within 30 days (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.07 to 1.28) and 9% greater risk within 1 year (HR 1.09, 95% CI 1.03 to 1.15). LOS of 11 to 29 days was associated with increased readmission risk of 52% at 30 days (HR 1.52, 95% CI 1.30 to 1.76) and 25% at 1 year (HR 1.25, 95% CI 1.16 to 1.35). Mortality risk within 30 days among those with LOS of 1 day was 47% lower (HR 0.53, 95% CI 0.43 to 0.65) and 32% lower at 1 year (HR 0.68, 95% CI 0.62 to 0.74). LOS of 2 days was associated with lower mortality risk of 17% (HR 0.83, 95% CI 0.76 to 0.90) at 1 year. At LOS 5 to 10 days, 30-day and 1-year risk of mortality was increased by 52% (HR 1.52, 95% CI 1.30 to 1.76) and 25% (HR 1.25, 95% CI 1.16 to 1.35), respectively. LOS of 11 to 29 days was associated with 171% higher mortality risk at 30 days (HR 2.71, 95% CI 2.19 to 3.35) and 73% at 1 year (HR 1.73, 95% CI 1.53 to 1.97). Longer LOS during the index HF hospitalization was associated with readmission and mortality within 30 days and 1 year independent of co-morbidities and cardiovascular risk factors. These results suggest that LOS may be a proxy for the severity of HF during the index hospitalization. [ABSTRACT FROM AUTHOR]

Purpose: To examine the psychometric properties and validity of the 8-item Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS-8) in postmenopausal women prescribed bisphosphonates (BPs) for at least 15 months. Methods: A random sample of women aged ≥55 years with osteoporosis prescribed daily or weekly BPs was identified. Pharmacy fill data were extracted to calculate the medication possession ratio (MPR). Eligible women were stratified by low (<0.50), medium (0.50-0.79), or high (≥0.80) MPR, with the a priori goal of recruiting 133 participants in each group. OS-MMAS-8 scores can range from 0 to 8 and were categorized as low (<6), medium (6 to <8), and high (8) adherence. Internal consistency reliability (Cronbach's alpha), test-retest reliability [intraclass correlation coefficients (ICCs)] and convergent validity (correlating OS-MMAS-8 with MPR and other self-reported measures) were assessed. Results: A total of 400 women out of 449 respondents reported that they were still taking their BPs at the time of the survey and completed OS-MMAS-8. Overall, 38.5, 34.3, and 27.3 % of participants had low, medium, and high OS-MMAS-8 scores, respectively. The mean (SD) MPRs according to OS-MMAS-8 scores (<6, 6 to <8 and 8) were 56.9 (22.6), 69.0 (24.9), and 76.7 (26.4), respectively. The correlation between OS-MMAS-8 and MPR was 0.36; p < 0.0001. Cronbach's alpha was 0.74, and the ICC was 0.83 (95 % CI 0.76-0.88). Conclusions: OS-MMAS-8 has acceptable psychometric properties for assessing medication adherence in postmenopausal women prescribed therapy for osteoporosis. Additional studies are needed to investigate the psychometric properties of OS-MMAS-8 in other settings and populations. [ABSTRACT FROM AUTHOR]

The article reports on research which evaluated the effects of folic acid supplementation on the risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among people with preexisting cardiovascular or renal disease. Researchers found that Folic acid supplementation has not been shown to reduce the risk of cardiovascular diseases or all-cause mortality. A discussion of the mortality rate in the United States and worldwide which is associated with cardiovascular disease is presented.

Abstract: Purpose: The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease. Methods: A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted. Results: Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition. Conclusion: This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population. [Copyright &y& Elsevier]

Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (−5.26 mg/dl, 95% confidence interval [CI] −7.14 to −3.38), low-density lipoprotein cholesterol (−4.25 mg/dl, 95% CI −6.00 to −2.50), and triglycerides (−6.26 mg/dl, 95% CI −9.14 to −3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors. [Copyright &y& Elsevier]

Background: The metabolic syndrome and obesity are major risk factors for cardiovascular disease. Little information exists on the prevalence of the metabolic syndrome in China. We aimed to provide up-to-date estimates of the prevalence of the metabolic syndrome and overweight in the general adult population in China. Methods: We did a cross-sectional survey in a nationally representative sample of 15 540 Chinese adults aged 35--74 years in 2000 --01. Metabolic syndrome was defined according to guidelines from the US National Cholesterol Education Program. Overweight was defined as body-mass index of 25.0 kg/m2 or greater. Findings: The age-standardised prevalence of metabolic syndrome was 9.8% (95% CI 9.0--10.6) in men and 17.8% (16.6--19.0) in women. The age-standardised prevalence of overweight was 26.9% (25.7--28 .1) in men and 31.1% (29.7--32.5) in women. The prevalence of the metabolic syndrome and overweight was higher in northern than in southern China, and higher in urban than rural residents. Interpretation: Our results indicate that a large proportion of Chinese adults have the metabolic syndrome and that overweight has become an important public health problem in China. These findings emphasise the urgent need to develop national strategies for the prevention, detection, and treatment of overweight and the metabolic syndrome, to reduce the societal burden of cardiovascular disease in China. [ABSTRACT FROM AUTHOR]

Context: Observational studies suggest that heavy alcohol consumption may increase the risk of stroke while moderate consumption may decrease the risk. Objective: To examine the association between alcohol consumption and relative risk of stroke. Data Sources: Studies published in English-language journals were retrieved by searching MEDLINE (1966–April 2002) using Medical Subject Headings alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke; Dissertation Abstracts Online using the keywords stroke and alcohol; and bibliographies of retrieved articles. Study Selection: From 122 relevant retrieved reports, 35 observational studies (cohort or case control) in which total stroke, ischemic stroke, or hemorrhagic (intracerebral or total) stroke was an end point; the relative risk or relative odds and their variance (or data to calculate them) of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and abstainers served as the reference group. Data Extraction: Information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, and risk estimates was abstracted independently by 3 investigators using a standardized protocol. Data Synthesis: A random-effects model and meta-regression analysis were used to pool data from individual studies. Compared with abstainers, consumption of more than 60 g of alcohol per day was associated with an increased relative risk of total stroke, 1.64 (95% confidence interval [CI], 1.39-1.93); ischemic stroke, 1.69 (95% CI, 1.34-2.15); and hemorrhagic stroke, 2.18 (95% CI, 1.48-3.20), while consumption of less than 12 g/d was associated with a reduced relative risk of total stroke, 0.83 (95%, CI, 0.75-0.91) and ischemic stroke, 0.80 (95% CI, 0.67-0.96), and consumption of 12 to 24 g/d was associated with a reduced relative... [ABSTRACT FROM AUTHOR]

Background: The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. Methods: We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70–189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. Results: We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. Conclusions: These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment. [ABSTRACT FROM AUTHOR]

ABSTRACT Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) have demonstrated a blood pressure (BP) reduction benefit despite other indications for use. We evaluated BP changes and antihypertensive medication use pre‐ and post‐SGLT2i initiation among 12 960 patients with treated hypertension and among subgroups with apparent treatment‐resistant hypertension (aTRH) and/or proteinuria. Post‐SGLT2i initiation, the mean (SD) systolic blood pressure (SBP) was reduced from 133.9 (16.4) to 128.6 (15.5) mmHg and the mean diastolic blood pressure (DBP) was reduced from 70.8 (11.8) to 68.3 (11.3) mmHg among all patients. The mean SBP/DBP reduction was 5.3/2.5, 6.2/2.8, and 6.1/2.9 mmHg among all patients, patients with aTRH, and patients with proteinuria, respectively. Achieved BP < 130/80 mmHg increased by 12.5%, 16.9%, and 11.1% for all patients, patients with aTRH, and patients with proteinuria, respectively. Discontinuation of ≥ 1 antihypertensive medication within 12 months of SGLT2i initiation occurred in 33.4% overall, 47.6% of patients with aTRH, and 38.7% of patients with proteinuria. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To compare A1C and fasting glucose for the diagnosis of diabetes among U.S. adults. RESEARCH DESIGN AND METHODS -- This study included 6,890 adults (≥20 years of age) from the 1999-2006 National Health and Nutrition Examination Survey without a self-reported history of diabetes who had fasted ≥9 h. A1C ≥6.5% and fasting glucose ≥126 mg/dl were used, separately, to define diabetes. RESULTS -- Overall, 1.8% of U.S. adults had A1C ≥6.5% and fasting glucose ≥126 mg/dl, 0.5% had A1C ≥6.5% and fasting glucose <126 mg/dl, and 1.8% had A1C <6.5% and fasting glucose ≥ 126 mg/dl. Compared with individuals with A1C <6.5% and fasting glucose ≥ 126 mg/dl, individuals with A1C ≥6.5% and fasting glucose < 126 mg/dl were younger, more likely to be non-Hispanic black, had lower Hb levels, and had higher C-reactive protein. CONCLUSIONS -- A1C ≥ 6.5% demonstrates reasonable agreement with fasting glucose for diagnosing diabetes among U.S. adults. [ABSTRACT FROM AUTHOR]

Background: Less than 50% of non-Hispanic Asian adults taking antihypertensive medication have controlled blood pressure. Methods: We compared non-persistence and low adherence to antihypertensive medication between non-Hispanic Asian and other race/ethnicity groups among US adults ≥66 years who initiated antihypertensive medication between 2011 and 2018 using a 5% random sample of Medicare beneficiaries (non-Hispanic Asian, n = 2,260; non-Hispanic White, n = 56,000; non-Hispanic Black, n = 5,792; Hispanic, n = 4,212; and Other, n = 1,423). Non-persistence was defined as not having antihypertensive medication available to take in the last 90 of 365 days following treatment initiation. Low adherence was defined as having antihypertensive medication available to take on <80% of the 365 days following initiation. Results: In 2011–2012, 2013–2014, 2015–2016 and 2017–2018, the proportion of non-Hispanic Asian Medicare beneficiaries with non-persistence was 29.1%, 25.6%, 25.4% and 26.7% (p-trend = 0.381), respectively, and the proportion with low adherence was 58.1%, 54.2%, 53.4% and 51.6%, respectively (p-trend = 0.020). In 2017–2018, compared with non-Hispanic Asian beneficiaries, non-persistence was less common among non-Hispanic White beneficiaries (risk ratio 0.74 [95%CI, 0.64–0.85]), non-Hispanic Black beneficiaries (0.80 [95%CI 0.68–0.94]) and those reporting Other race/ethnicity (0.68 [95%CI, 0.54–0.85]) but not among Hispanic beneficiaries (1.04 [95%CI, 0.88–1.23]). Compared to non-Hispanic Asian beneficiaries, non-Hispanic White beneficiaries and beneficiaries reporting Other race/ethnicity were less likely to have low adherence to antihypertensive medication (relative risk 0.78 [95%CI 0.72–0.84] and 0.84 [95%CI 0.74–0.95], respectively); there was no association for non-Hispanic Black or Hispanic beneficiaries. Conclusions: Non-persistence and low adherence to antihypertensive medication were more common among older non-Hispanic Asian than non-Hispanic White adults. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest. RESULTS: Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P < 0.0001), depressive symptoms (P < 0.0001), and decreased health-related (P < 0.0001) and diabetes-specific quality of life (P < 0.0001). CONCLUSIONS: Diabetes stigma is associated with food insecurity, disordered eating, and lower psychosocial well-being. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.Methods: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. The receipt of potentially cardiotoxic breast cancer treatments was indicated if the patient received anthracyclines or hormone therapies. We modeled the outcomes of post-cancer diagnosis CHD and death, respectively.Results: Results of these approaches indicated that the joint effect of poor CVH and receipt of cardiotoxic treatments on CHD (75.9%) and death (39.5%) was significantly higher than their independent effects [poor CVH (55.9%) and cardiotoxic treatments (43.6%) for CHD, and poor CVH (29.4%) and cardiotoxic treatments (35.8%) for death].Conclusions: Better CVH appears to be protective against the development of CHD even among women who had received potentially cardiotoxic treatments. This study determined the extent to which attainment of ideal CVH is important not only for CHD and mortality outcomes among women diagnosed with breast cancer. [ABSTRACT FROM AUTHOR]

Background: Older adults with chronic kidney disease (CKD)-discordant conditions (comorbid conditions with treatment recommendations that potentially complicate CKD management) have higher risk of hospitalization and death. Our goal is to develop a CKD-Discordance Index using electronic health records to improve recognition of discordance.Methods: This retrospective cohort study included Kaiser Permanente Southern California patients aged ≥65 years and older with incident CKD (N = 30,932). To guide inclusion of conditions in the Index and weight each condition, we first developed a prediction model for 1-year hospitalization risk using Cox regression. Points were assigned proportional to regression coefficients derived from the model. Next, the CKD-Discordance Index was calculated as an individual's total points divided by the maximum possible discordance points. The association between CKD-Discordance Index and hospitalizations, emergency department visits, and mortality was accessed using multivariable-adjusted Cox regression model.Results: Overall, mean (SD) age was 77.9 (7.6) years, 55% of participants were female, 59.3% were white, and 32% (n = 9,869) had ≥1 hospitalization during 1 year of follow-up. The CKD-Discordance Index included the following variables: heart failure, gastroesophageal reflux disease/peptic ulcer disease, osteoarthritis, dementia, depression, cancer, chronic obstructive pulmonary disease/asthma, and having four or more prescribers. Compared to those with a CKD-Discordance Index of 0, adjusted hazard ratios (95% confidence interval) for hospitalization were 1.39 (1.27-1.51) and 1.81 (1.64-2.01) for those with a CKD-Discordance Index of 0.001-0.24 and ≥0.25, respectively (ptrend < .001). A graded pattern of risk was seen for emergency department visits and all-cause mortality.Conclusion: A data-driven approach identified CKD-discordant indicators for a CKD-Discordance Index. Higher CKD-Discordance Index was associated with health care utilization and mortality. [ABSTRACT FROM AUTHOR]

Objective This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral transmission to the infant. Study Design A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020–February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes. Results Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 [5.4] vs. 31.1 [5.3] years; mean [standard deviation (SD)]; p <.001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval [CI]: 1.00, 1.21; p = 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58; p = 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50; p = 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62; p < 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33; p = 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period. Conclusion These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission. Key Points SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes. The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy. The proportion of vertical transmission from mother to fetus was 0.3% [ABSTRACT FROM AUTHOR]

Aim: To determine whether high triglycerides (TG) in the presence of statin‐controlled LDL‐C influence the risk of cardiovascular disease (CVD) among patients with diabetes in real‐world clinical practice. Materials and methods: We identified adults with diabetes from the Southern California and Pacific Northwest regions of Kaiser Permanente. We included patients undergoing statin therapy with LDL‐C from 40‐100 mg/dL who were not undergoing other lipid‐lowering therapies and had a prior diagnosis of atherosclerotic CVD or at least one other CVD risk factor. We grouped patients into high TG (200‐499 mg/dL; n = 5542) or normal TG (<150 mg/dL, n = 22 411) from January 2010 through December 2016 to compare incidence rates and rate ratios of first non‐fatal myocardial infarction (MI), non‐fatal stroke, unstable angina and coronary revascularization. We adjusted multivariable analyses for age, sex, race/ethnicity, smoking status, blood pressure, HbA1c, serum creatinine, presence of ischaemic heart disease and study site. Results: Adjusted rate ratios for the four outcomes were all statistically significantly different. The incidence rate for non‐fatal MI was 30% higher in the high TG group (rate ratio, 1.30; 95% CI, 1.08‐1.58; P = 0.006). The rate was 23% higher for non‐fatal stroke (1.23, 1.01‐1.49, P = 0.037), 21% higher for coronary revascularization (rate ratio, 1.21; 95% CI, 1.02‐1.43; P = 0.027) and was, non‐significantly, 33% higher for unstable angina (rate ratio, 1.33; 95% CI, 0.87‐2.03; P = 0.185). Conclusions: Despite statin‐controlled LDL‐C levels, CV events were greater among patients with diabetes and high TG levels. Because we controlled for cardiometabolic risk factors, it is likely that the difference in TG levels contributed to the excess risk observed in patients with high TGs. [ABSTRACT FROM AUTHOR]

Discusses issues concerning the metabolic syndrome, a cluster of cardiovascular risk factors frequently associated with insulin resistance. Lack of records on the syndrome; Concern that reimbursement will not be provided if the metabolic syndrome is listed as an ICD-9 code; Establishment of the diagnosis of the metabolic syndrome.

Successful transition from a pediatric to adult diabetes care provider is associated with reduced ambulatory diabetes care visits and increased acute complications. This study aimed to determine whether the degree of independence in diabetes care and the rate of acute complications after transition to adult diabetes care were associated with individuals' student or employment status. Nonstudents were found to be less likely than students to be independent with diabetes care, and employed nonstudents were at lower risk of diabetic ketoacidosis than unemployed nonstudents. Additional support may be needed for young adults who are not students or are unemployed to improve independence and reduce the risk for acute complications. [ABSTRACT FROM AUTHOR]

Despite their effectiveness in reducing low-density lipoprotein cholesterol and cardiovascular disease risk, high-intensity statins are underutilized among adults with low-density lipoprotein cholesterol ≥190 mg/dL. This study determined whether a safety net program (SureNet) facilitating medication and laboratory test orders improved statin initiation and laboratory test completions after (SureNet period: April 2019–September 2021) and before implementation (pre-SureNet period: January 2016–September 2018). Kaiser Permanente Southern California members aged 20–60 years with low-density lipoprotein cholesterol ≥190 mg/dL and no statin use in previous 2–6 months were included in this retrospective cohort study. Statin orders within 14 days and statin fills, laboratory test completions, and improved low-density lipoprotein cholesterol within 180 days of the high low-density lipoprotein cholesterol (pre-SureNet) or outreach (SureNet period) were compared. Analyses were conducted in 2022. Overall, 3,534 and 3,555 adults were eligible for statin initiation during the pre-SureNet and SureNet periods, respectively. Overall, 759 (21.5%) and 976 (27.5%) had a statin approved by their physician during pre-SureNet and SureNet periods, respectively (p <0.001). After multivariable adjustment for demographics and clinical characteristics, adults during the SureNet period had a higher likelihood of receiving a statin order (prevalence ratio=1.36, 95% CI=1.25, 1.48), filling their statin (prevalence ratio=1.32, 95% CI=1.26, 1.38), completing their laboratories (prevalence ratio=1.41, 95% CI=1.26, 1.58), and improving low-density lipoprotein cholesterol (prevalence ratio=1.21, 95% CI=1.07, 1.37) than in pre-Surenet period. The SureNet program was able to improve prescription orders, fills, laboratory test completions, and lower low-density lipoprotein cholesterol. Optimizing both physician adherence to treatment guidelines; and patient adherence to the program may improve low-density lipoprotein cholesterol lowering. [ABSTRACT FROM AUTHOR]

• Monitoring the safety of vaccines containing novel adjuvants is important. • Risk of new-onset immune-mediated events after HepB-CpG versus HepB-alum was similar. • The risk of herpes zoster was not increased after HepB-CpG compared with HepB-alum. • No cases of anaphylaxis occurred after receipt of HepB-CpG. • This study did not identify safety concerns of HepB-CpG compared with HepB-alum. HepB-CpG (Heplisav-B) is a licensed hepatitis B vaccine with a novel adjuvant that requires 2 doses (0, 1 month) compared to HepB-alum (Engerix-B) which requires 3 doses (0, 1, 6 months). Monitoring safety outcomes following receipt of vaccines with novel adjuvants outside trial settings is important. Hence, as part of a post-marketing commitment, we compared the incidence of new-onset immune-mediated diseases, herpes zoster (HZ), and anaphylaxis among recipients of HepB-CpG versus HepB-alum. This cohort study included adults not on dialysis who received ≥1 dose of hepatitis B vaccine from 8/7/2018 to 10/31/2019, during which HepB-CpG was routinely administered in 7 of 15 Kaiser Permanente Southern California medical centers while HepB-alum was administered in the other 8 centers. Recipients of HepB-CpG or HepB-alum were followed through electronic health records for 13 months for occurrence of pre-specified new-onset immune-mediated diseases, HZ, and anaphylaxis identified using diagnosis codes. Incidence rates were compared using Poisson regression with inverse probability of treatment weighting when there was ≥80 % power to detect a relative risk (RR) of 5 for anaphylaxis and RR of 3 for other outcomes. Chart review to confirm new-onset diagnosis was conducted for outcomes with statistically significant elevated risk. There were 31,183 HepB-CpG and 38,442 HepB-alum recipients (overall 49.0 % female, 48.5 % age ≥50 years, and 49.6 % Hispanic). Among immune-mediated events that occurred frequently enough for formal comparison, rates among HepB-CpG versus Hep-B-alum recipients were similar except for rheumatoid arthritis (RA) (adjusted RR 1.53 [95 % CI: 1.07, 2.18]). After chart confirmation of new-onset RA, the adjusted RR was 0.93 (0.34, 2.49). The adjusted RR for HZ was 1.06 (0.89, 1.27). Anaphylaxis occurred in 0 HepB-CpG and 2 HepB-alum recipients. This large post-licensure study did not identify evidence of safety concerns for HepB-CpG compared to HepB-alum for immune-mediated diseases, HZ, or anaphylaxis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002–2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) treatment requires complex management, and patients with limited health literacy (HL) may perceive higher burden and lower benefits associated with their treatment. Objective: To examine the association of HL with treatment satisfaction among patients with VTE. Design: Retrospective cohort study Participants: Kaiser Permanente Southern and Northern California members who were taking oral anticoagulants (OAC) for incident VTE between 2015 and 2018 were surveyed. Main Measures HL was assessed using a 3-item HL assessment and dichotomized as having adequate or limited HL. High treatment burden and low treatment benefit were defined as Anti-Clot Treatment Scale (ACTS) scores below the 25th percentile of the distributions for ACTS Burdens and Benefits survey components, respectively. Using Poisson regression, multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) were calculated for the association of HL with high treatment burden and low treatment benefits. Results: Among 2154 respondents, 397 (18.4%) had limited HL. Patients with limited vs adequate HL were older (47.9% vs 27.5% aged ≥ 75 years, p<0.001), more likely to use a non-English language when discussing their health (10.8% vs 1.7%, p<0.001), to have less than high school education (10.1% vs 1.7%, p<0.001), and to self-rate their health as fair or poor (47.6% vs 25.5%, p<0.001). After multivariable adjustment, patients with limited HL were more likely to have higher perceived treatment burden (RR 1.24, 95% CI 1.07, 1.45) and lower perceived treatment benefits (RR 1.21, 95% CI 1.08, 1.37). Conclusions: Limited HL was associated with lower OAC treatment satisfaction, though absolute differences in satisfaction scores were small. Further examination of the intersection of HL with VTE treatment satisfaction and compliance among older and non-English speaking patients is warranted. [ABSTRACT FROM AUTHOR]

Introduction: In the United States, there has been controversy over whether treatment of mild‐to‐moderate hypertension during pregnancy conveys more benefit than risk. Objective: The objective of the study was to compare risks and benefits of treatment of mild‐to‐moderate hypertension during pregnancy. Methods: This retrospective cohort study included 11,871 pregnant women with mild‐to‐moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small‐for‐gestational‐age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre‐pregnancy body mass index) analyses were also conducted. Results: In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: −0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. Conclusions: Initiation of antihypertensive medication at mild‐to‐moderate BP thresholds (140–155/90–105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between diabetes stigma and HbA1c, treatment plan and acute and chronic complications in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study is a multicenter cohort study that collected questionnaire, laboratory, and physical examination data about AYAs with diabetes diagnosed in childhood. A five-question survey assessed frequency of perceived diabetes-related stigma, generating a total diabetes stigma score. We used multivariable linear modeling, stratified by diabetes type, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic characteristics, clinic site, diabetes duration, health insurance, treatment plan, and HbA1c. RESULTS: Of 1,608 respondents, 78% had type 1 diabetes, 56% were female, and 48% were non-Hispanic White. The mean (SD) age at study visit was 21.7 (5.1) years (range, 10–24.9). The mean (SD) HbA1c was 9.2% (2.3%; 77 mmol/mol [2.0 mmol/mol]). Higher diabetes stigma scores were associated with female sex and higher HbA1c (P < 0.01) for all participants. No significant association between diabetes stigma score and technology use was observed. In participants with type 2 diabetes, higher diabetes stigma scores were associated with insulin use (P = 0.04). Independent of HbA1c, higher diabetes stigma scores were associated with some acute complications for AYAs with type 1 diabetes and some chronic complications for AYAs with type 1 or type 2 diabetes. CONCLUSIONS: Diabetes stigma in AYAs is associated with worse diabetes outcomes and is important to address when providing comprehensive diabetes care. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) social distancing policies resulted in reductions in community movement, however, fall rates during this time have not been described. Methods This prospective study included adults ≥65 years old participating in the Ambulatory Blood Pressure in Older Adults (AMBROSIA) cohort and who completed ≥1 monthly falls calendar (August 2019–March 2021; n = 250). Months were grouped to correspond to the fall 2020 phased reopening (August–October) and the shelter-in-place policy during the winter 2020 surge (November–January) in Los Angeles, California and compared to the same months, 1 year earlier (ie, before the pandemic). Results Participants had a mean (standard deviation [ SD ]) age of 75.2 (6.1) years, 49.6% were White, and 53.2% were women. We obtained 2 795 falls calendars during follow-up. Overall, 110 (44.0%) participants reported a total of 421 falls (rate 15.1 per 100 calendar months). The highest monthly fall rate during the pandemic was 22.9 (95% confidence interval [CI] 16.4–31.1) per 100 calendar-months in August 2020. The lowest fall rate during the pandemic was 8.6 (95% CI 3.5–17.8) per 100 calendar-months in February 2021. During the pandemic, fall rates in August, September, and October 2020 were higher than the previous year (rate ratio 1.8 [95% CI 1.1–2.9]), and fall rates in November and December 2020 and January 2021 were lower than the previous year (rate ratio 0.5 [95% CI 0.4–0.8]). Conclusion As the pandemic continues and older adults resume community mobility after a shelter-in-place period, providers should pay attention to the risk of falls. [ABSTRACT FROM AUTHOR]

Young adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. In this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. We included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. Among 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell's C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. Long-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk. [Display omitted] [ABSTRACT FROM AUTHOR]

The article presents a response by Lydia A. Bazzano and colleagues to letters to the editor about their article "Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials," in a previous issue.

The Anticoagulation Length of Therapy and Risk of New Adverse Events In Venous Thromboembolism (ALTERNATIVE) study was designed to compare the benefits and harms of different treatment options for extended treatment of venous thromboembolism (VTE). In this paper, we describe the study cohort, survey data collection, and preliminary results. We identified 39,605 adult patients (age ≥ 18 years) from two large integrated health care delivery systems who were diagnosed with incident VTE and received initial anticoagulation therapy of 3 months or longer. A subset of the cohort (12,737) was invited to participate in a survey. Surveys were completed in English, Spanish or Mandarin via a mailed questionnaire, an online secure web link, or telephone. The survey domains included demographics, personal medical history, anticoagulant treatment history, anticoagulant treatment satisfaction, health-related quality of life and health literacy. A total of 5,017 patients participated in the survey for an overall response rate of 39.4%. The mean (SD) age of the survey respondents was 63.0 (14.5) years and self-reported race was 76.0% White/European, 11.1% Black/African American, and 3.8% Asian/Pacific Islander and 14.0% reported Hispanic ethnicity. Sixty percent of respondents completed the web survey, while 29.0% completed the mail-in paper survey, and 11.0% completed the survey via telephone. The ALTERNATIVE Study will address knowledge gaps by comparing several treatment alternatives for the extended management of VTE so that this information could be used by patients and clinicians to make more informed, patient-centered treatment choices. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The use of statins increased among US adults with high coronary heart disease (CHD) risk after publication of the 2001 cholesterol treatment guidelines.Methods and Results: We analyzed the association between lipids and CHD among 9578 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and 346,595 Kaiser Permanente Southern California (KPSC) members with baseline lipid measurements in 2003 to 2007. We performed the same analyses among 14,590 Atherosclerosis Risk In Communities (ARIC) study participants with lipid measurements in 1987 to 1989. Analyses were restricted to blacks and whites 45 to 64 years of age without CHD who were not taking statins at baseline. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline. Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and ratios of total to high-density lipoprotein cholesterol and triglycerides to high-density lipoprotein cholesterol were calculated. The prevalence of diabetes mellitus, history of stroke, and antihypertensive medication use increased at higher low-density lipoprotein cholesterol in ARIC but not in REGARDS or KPSC. Over 8.9 years of follow-up, 225 CHD events occurred in REGARDS, 6547 events in KPSC, and 583 events in ARIC. After multivariable adjustment, less favorable lipid levels were associated with higher hazard ratios for CHD in ARIC. These associations were attenuated in REGARDS and KPSC. For example, the hazard ratio associated with the highest versus lowest quartile of low-density lipoprotein cholesterol (≥ 146 versus ≤ 102 mg/dL) was 1.89 (95% confidence interval, 1.42-2.51) in ARIC, 1.25 (95% confidence interval, 0.81-1.92) in REGARDS, and 1.49 (95% confidence interval, 1.38-1.61) in KPSC.Conclusion: The association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the association between hydroxymethylglutaryl-CoA inhibitor (statin) use and hip fracture.Methods: We conducted a population-based case-control study. Cases were 6774 male enrollees in a large managed care organization, aged 45 or more years, with an incident hip fracture from 1997 to 2006. Controls without fracture (n = 6774) were matched to cases on age, race, and medical center. Electronic information on pharmaceutical use was used to identify the dispensing of statins from 1991 forward.Results: Overall, 1884 (27.8%) cases and 2150 controls (31.7%) used a statin before index date (matched odds ratio [mOR] = 0.81, 95% confidence interval [CI] = 0.74-0.87). Adjustment for comorbidity burden strengthened the magnitude of the overall association (mOR = 0.68, CI = 0.62-0.74). The adjusted association was similar across age groups but was strongest among men aged 80 years or more (mOR = 0.62, CI = 0.54-0.71) and was most pronounced in African Americans (mOR = 0.43, CI = 0.28-0.64). Greater duration of statin use did not alter the odds ratios.Conclusions: These data add to the growing evidence of a potential protective effect of statin use on bone health. However, these results need to be replicated in a prospective study that can account for confounding by indication which may explain these findings. [ABSTRACT FROM AUTHOR]

Background: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood. Setting: Integrated health care system. Methods: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex. Results: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200–499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively). Conclusions: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users. We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics. Overall, 2230 patients (43.1 % women and 31.8 % >75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users. Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE. • Health-related quality of life (QOL) is a key outcome measure in venous thromboembolism (VTE). • Little is known about differences in QOL for patients prescribed warfarin versus direct oral anticoagulants (DOACs). • We assessed QOL using RAND 36-item Short Form Health Survey (SF-36) in patients with VTE in Kaiser integrated healthcare system. • Among 2230 patients, there were no significant differences in physical or mental QOL scores between warfarin and DOAC users. [ABSTRACT FROM AUTHOR]

Background: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. Objective: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. Design, Setting, and Participants: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. Exposure: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). Main Outcomes: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. Results: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). Conclusions: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF. [ABSTRACT FROM AUTHOR]

To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in recent clinical care. We evaluated this association in the large Anticoagulation and Risk Factors in Atrial fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (CVRN) California community-based cohorts of patients with AF (study years 1996 to 2003 and 2006 to 2009, respectively), where all events were clinician adjudicated. We used proportional hazards regression with propensity score adjustment to estimate the short- (30 days) and long-term (>30 days for 1 year) mortality rate ratio for patients using warfarin compared with those who were not using warfarin at the time of GI hemorrhage. In the 414 ATRIA participants with major GI hemorrhage, 54% were taking warfarin at the time of the hemorrhage; in the 361 ATRIA-CVRN participants with major GI hemorrhage, 58% were taking warfarin. Warfarin use at the time of GI hemorrhage was not associated with 30-day mortality in the ATRIA cohort but was associated with significantly reduced 30-day mortality in the ATRIA-CVRN cohort (adjusted mortality rate ratio [95% confidence interval], ATRIA 0.97 [0.54 to 1.74]; ATRIA-CVRN 0.38 [0.17 to 0.83]). There was a modest suggestion of lower mortality on warfarin after 30 days in both cohorts. In conclusion, our study demonstrates that GI hemorrhages on warfarin are certainly no worse and may be less life threatening than those occurring off warfarin. These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage and add another factor favoring anticoagulation in clinical decision making for patients with AF. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. Design: Retrospective cohort study. Setting: Kaiser Permanente, a large healthcare system in the United States. Population: Women aged 15–49 years with a singleton birth from 2005–2014 treated for hypertension. Methods: We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Main outcome measures: Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Results: Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Conclusions: Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration. [ABSTRACT FROM AUTHOR]

Background: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.Objective: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.Design: A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271).Setting: A large academic medical center.Participants: 148 men and women without clinical cardiovascular disease and diabetes.Intervention: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.Measurements: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.Results: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet.Limitation: Lack of clinical cardiovascular disease end points.Conclusion: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]