Takahashi, Paul Y.

Background Larger within‐patient variability of lipid levels has been associated with increased risk of cardiovascular disease (CVD); however, measures of lipid variability require ≥3 measurements and are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record–based population cohort and assessed associations with incident CVD. Methods and Results We identified all individuals ≥40 years of age who resided in Olmsted County, MN, on January 1, 2006 (index date), without prior CVD, defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or CVD death. Patients with ≥3 measurements of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, or triglycerides during the 5 years before the index date were retained. Lipid variability was calculated using variability independent of the mean. Patients were followed through December 31, 2020 for incident CVD. We identified 19 652 individuals (mean age 61 years; 55% female), who were CVD‐free and had variability independent of the mean calculated for at least 1 lipid type. After adjustment, those with highest total cholesterol variability had a 20% increased risk of CVD (Q5 versus Q1 hazard ratio, 1.20 [95% CI, 1.06–1.37]). Results were similar for low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Conclusions In a large electronic health record–based population cohort, high variability in total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol was associated with an increased risk of CVD, independent of traditional risk factors, suggesting it may be a possible risk marker and target for intervention. Lipid variability can be calculated in the electronic health record environment, but more research is needed to determine its clinical utility.

Importance Little is known about the burden and outcomes of respiratory syncytial virus (RSV)–positive acute respiratory infection (ARI) in community-dwelling older adults. Objective To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure RSV-positive and -negative ARI. Main Outcomes and Measures RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, −16.7 [95% CI, −31.8 to −1.8]; fatigue, −8.4 [95% CI, −14.3 to −2.4]; and difficulty in social functioning, −11.9 [95% CI, −19.8 to −4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: −4.0 [95% CI, −8.5 to −1.3]; difficulty in social functioning, −5.8 [95% CI, −10.3 to −1.3]; and limitation due to emotional problem, −7.0 [95% CI, −12.7 to −1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, −4.4 [95% CI, −7.3 to −1.5]; difficulty in social functioning, −5.2 [95% CI, −8.7 to −1.7] and limitation due to emotional problem, −5.7 [95% CI, −10.7 to −0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Abstract Context Metformin is the first-line drug for treating diabetes but has a high failure rate. Objective To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure. Methods A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota). We identified 22 047 metformin initiators (48% female, mean age of 57 ± 14 years) including 2141 African Americans, 440 Asians, 962 Other/Multiracial, 1539 Hispanics, and 16 764 non-Hispanic White people. We defined metformin failure as either the lack of a target glycated hemoglobin (HbA1c) (<7%) within 18 months of index or the start of dual therapy. We used tree-based extreme gradient boosting (XGBoost) models to assess overall risk prediction performance and relative contribution of individual factors when using EHR data for risk of metformin failure. Results In this large diverse population, we observed a high rate of metformin failure (43%). The XGBoost model that included baseline HbA1c, age, sex, and race/ethnicity corresponded to high discrimination performance (C-index of 0.731; 95% CI 0.722, 0.740) for risk of metformin failure. Baseline HbA1c corresponded to the largest feature performance with higher levels associated with metformin failure. The addition of other clinical factors improved model performance (0.745; 95% CI 0.737, 0.754, P < .0001). Conclusion Baseline HbA1c was the strongest predictor of metformin failure and additional factors substantially improved performance suggesting that routinely available clinical data could be used to identify patients at high risk of metformin failure who might benefit from closer monitoring and earlier treatment intensification.

Abstract Objectives People with dementia often have high care needs at end of life. We compared care delivery in the last year of life for people living with dementia in the community (home/assisted living facilities, ALF) to those in skilled nursing facilities (SNF). Methods This was a retrospective study of people who died with a diagnosis of dementia in the community compared with SNF between 2013 and 2018. Primary outcomes of hospitalizations/ED visits in the last year of life were measured. Secondary outcomes included advance care planning (ACP) completion, hospice enrollment, provider visits and ICU admissions. Results Of 1203 people with dementia, 581 (48.3%) were living in a SNF and 622 (51.7%) in the home/ALF. At least one hospitalization was recorded for 70.7% in the home/ALF compared with 50.8% in the SNF (p< 0.01), similar to ED visits (80.2% versus 58% in home/ALF and SNF groups, respectively, p< 0.01). People in the SNF had more provider visits (median 9 (IQR 6, 12) compared with 5 (IQR 3,9) in the home/ALF group (p< 0.01). There was no ACP for 12% of those in the home/ALF, compared with 4.6% in the SNF(p< 0.01). Approximately half (56.5%) in the SNF were enrolled in hospice compared with 68.3% in the home/ALF group (p< 0.01), Median time in hospice was 26.5 days in the SNF versus 30 days in the home/ALF (p=0.67). Conclusions People living with dementia have frequent acute care utilization in the last year of life. Hospice care was more common in the home/ALF. Time in hospice was short.

Objective People living with dementia often have high care needs at the end-of-life. We compared care delivery in the last year of life for people living with dementia in the community (home or assisted living facilities [ALFs]) versus those in skilled nursing facilities (SNFs). Methods A retrospective study was performed of older adults with a dementia diagnosis who died in the community or SNFs from 2013 through 2018. Primary outcomes were numbers of hospitalizations and emergency department visits in the last year of life. Secondary outcomes were completed advance care plans, hospice enrollment, time in hospice, practitioner visits, and intensive care unit admissions. Results Of 1203 older adults with dementia, 622 (51.7%) lived at home/ALFs; 581 (48.3%) lived in SNFs. At least 1 hospitalization was recorded for 70.7% living at home/ALFs versus 50.8% in SNFs ( P < .001), similar to percentages of emergency department visits (80.2% vs 58.0% of the home/ALF and SNF groups, P < .001). SNF residents had more practitioner visits than home/ALF residents: median (IQR), 9.0 (6.0-12.0) versus 5.0 (3.0-9.0; P < .001). No advance care plan was documented for 12.2% (n = 76) of the home/ALF group versus 4.6% (n = 27) of the SNF group ( P < .001). Nearly 57% of SNF residents were enrolled in hospice versus 68.3% at home/ALFs ( P < .001). The median time in hospice was 26.5 days in SNFs versus 30.0 days at home/ALFs ( P = .67). Conclusions Older adults with dementia frequently receive acute care in their last year of life. Hospice care was more common for home/ALF residents. Time in hospice was short.

Abstract BACKGROUND Uncertainty remains over the relationship between blood pressure (BP) variability (BPV), measured in hospital settings, and clinical outcomes following acute ischemic stroke (AIS). We examined the association between within-person systolic blood pressure (SBP) variability (SBPV) during hospitalization and readmission-free survival, all-cause readmission, or all-cause mortality 1 year after AIS. METHODS In a cohort of 862 consecutive patients (age [mean ± SD] 75 ± 15 years, 55% women) with AIS (2005–2018, follow-up through 2019), we measured SBPV as quartiles of standard deviations (SD) and coefficient of variation (CV) from a median of 16 SBP readings obtained throughout hospitalization. RESULTS In the cumulative cohort, the measured SD and CV of SBP in mmHg were 16 ± 6 and 10 ± 5, respectively. The hazard ratios (HR) for readmission-free survival between the highest vs. lowest quartiles were 1.44 (95% confidence interval [CI] 1.04–1.81) for SD and 1.29 (95% CI 0.94–1.78) for CV after adjustment for demographics and comorbidities. Similarly, incident readmission or mortality remained consistent between the highest vs. lowest quartiles of SD and CV (readmission: HR 1.29 [95% CI 0.90–1.78] for SD, HR 1.29 [95% CI 0.94–1.78] for CV; mortality: HR 1.15 [95% CI 0.71–1.87] for SD, HR 0.86 [95% CI 0.55–1.36] for CV). CONCULSIONS In patients with first AIS, SBPV measured as quartiles of SD or CV based on multiple readings throughout hospitalization has no independent prognostic implications for the readmission-free survival, readmission, or mortality. This underscores the importance of overall patient care rather than a specific focus on BP parameters during hospitalization for AIS.

AbstractBackground and AimsInfluenza is a challenging infectious illness for older adults. It is not completely clear whether influenza is associated with frailty or functional decline. We sought to determine the association between incident influenza infection and frailty and prefrailty in community patients over 50 years of age. We also investigated the association between influenza vaccination and frailty and prefrailty as a secondary aim.MethodsThis was a prospective community cohort study from October 2019 to November 2020 in participants over 50 years. The primary outcome was the development of frailty as defined by three of five frailty criteria (slow gait speed, low grip strength, 5% weight loss, low energy, and low physical functioning). The primary predictor was a positive polymerase chain reaction (PCR) for influenza infection. Influenza vaccination was based on electronic health record reviewing 1 year before enrollment. We reported the relationship between influenza and frailty by calculating odds ratios (OR) with 95% confidence intervals (CI) after adjustment for age, sex, socioeconomic status, Charlson Comorbidity Index (CCI), influenza vaccine, and previous self‐rated frailty from multinomial logistic regression model comparing frail and prefrail to nonfrail subjects.ResultsIn 1135 participants, the median age was 67 years (interquartile range 60−74), with 41% men. Eighty‐one participants had PCR‐confirmed influenza (7.1%). Frailty was not associated with influenza, with an OR of 0.50 (95% CI 0.17−1.43) for frail participants compared to nonfrail participants. Influenza vaccination is associated with frailty, with an OR of 1.69 (95% CI 1.09−2.63) for frail compared to nonfrail. Frailty was associated with a higher CCI with an OR of 1.52 (95% CI 1.31−1.76).ConclusionWe did not find a relationship between influenza infection and frailty. We found higher vaccination rates in participants with frailty compared to nonfrail participants While influenza was not associated with frailty, future work may involve longer follow‐up.

Abstract Work history is associated with long term health outcomes We hypothesize that characteristics of the first work experience, such as age at first job and length of work (hereafter job) are associated with future risk of hospitalization. We further hypothesize that the length of work will be associated with hospitalization. We conducted a survey of adults &gt;60 years using a nested case-control approach within the Mayo Clinic Biobank. We collected job related variables including age at job start, reason for ending, and length of time. To test associations between each variable and hospitalization, we used age and gender adjusted logistic regression models. Our study included 4,024 subjects: 1,801 cases and 2223 controls. The mean age at time of match was 77.3 years (SD 7.2 years) with 49.2% males. Older age at the first full-time job was associated with lower chance of hospitalization later in life (OR=0.81 [0.67, 0.97] for those who started the job over 22 compared to those started at 18 or less). Cases were more likely to have stopped working because of illness (OR=2.04 [95% CI 1.29,3.27]). Cases were less likely to have stopped working because of retirement (OR=0.82 [95% CI: 0.72, 0.93]). We found cases were employed with a slightly shorter time (20.5 yrs. (SD 16.6)) compared to controls (21.8 yrs. (SD 16.3)) (p=0.005). Cases started work earlier and stopped work more frequently because of illness/disability compared to controls. This could reflect educational attainment in controls. This study highlights work history as potential predictor of future hospitalization.

Background: Prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRDs) are urgently needed for reducing incidence. Intra-patient variability in lipid levels is a potentially modifiable risk factor for incident AD/ADRD. Although regular lipid measurements are a part of common clinical practice and longitudinal data routinely available in electronic health records (EHR), research examining this association between AD/ADRD and lipid variability across multiple lipid types remains scarce. Methods: All residents living in Olmsted County, MN on 1/1/2006 age ≥60 years without an AD/ADRD diagnosis were identified using Centers for Medicare & Medicaid Services diagnostic codes. Persons with ≥3 lipid measurements (total cholesterol or triglycerides) in the 5 years prior to index date were retained. Lipid variability was quantified using variability independent of the mean (VIM). Models were adjusted for traditional risk factors. Associations between lipid variability quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Multiple imputation was used for missing covariates. Participants were followed through 2018 for incident AD/ADRD. Results: The final analysis included data on 11,551 participants with total cholesterol and 11,502 participants with triglycerides. Participants had a mean age of 71 (range 60-99) years, and were primarily white (96%). Females (54%) were also slightly more frequent than males. Median follow up was 12.9 years (range: 0-13). Participants in the highest quintile of variability for total cholesterol and triglycerides had a 20% increased risk of incident AD/ADRD. Similar results were found in the subset with complete covariate data. Conclusion: In a large EHR derived cohort, persons in the highest quintile of lipid variation had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this risk factor and replication of these results across a more diverse population are needed.