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Minji K Lee,1 Jennifer L St Sauver,1,2 Roger T Anderson,3 Mark Linzer,4 David T Eton1,2 1Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA; 4Hennepin Healthcare, Minneapolis, Minnesota, USA, University of Minnesota Medical School, Minneapolis, MN, USACorrespondence: Minji K LeeRobert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Harwick Building, Second Floor, 200 First St SW, Rochester, MN 55905, USATel +1 507 284 1310Email Lee.Minji@mayo.eduDavid T Eton Email eton.david@mayo.eduPurpose: To examine the factor structure and differential item functioning (DIF) of the Patient Experience with Treatment and Self-management (PETS version 2.0), a measure of treatment burden.Patients and Methods: Version 2.0 of the PETS has 60 items, extending the previously-validated 48-item version 1.0 by three domains (nine items) and three additional items in an existing domain. We conducted confirmatory factor analyses (CFA) on survey responses of 439 community-dwelling adults living with multiple chronic conditions who completed PETS version 2.0, using R packages, “lavaan” and “semTools.” We tested fit of second-order factors to explore simplifying the reporting of PETS scores. We examined DIF for the two second-order factors with “lordif” R package, testing groups by gender, education, and health literacy, using the McFadden pseudo R2 change criterion of ≥ 0.02 to flag items with DIF. Cronbach’s alpha and the intraclass correlation coefficient (ICC) were used to determine the reliability of PETS domains.Results: The first-order CFA model featuring 12 multi-item domains had an excellent fit (Comparative Fit Index [CFI]=0.989), as did the second-order CFA model (CFI=0.987), specifying two superordinate factors of treatment burden (workload and impact). Items in the workload and impact second-order factors did not show any DIF across gender, education, and health literacy groups as shown by McFadden pseudo R2 changes < 0.02. Cronbach’s alphas for all multi-item domain scales were ≥ 0.80, and ICCs of ten scales were ≥ 0.70, meeting the threshold for adequate test–retest reliability.Conclusion: Findings support the construct validity and reliability of PETS version 2.0. The fit of a factor model featuring superordinate (ie, second-order) factors of workload and impact supports index scoring that will simplify reporting of PETS scores. DIF analyses indicate that items from these indices can be interpreted in the same way, regardless of gender, education, or health literacy.Keywords: factor structure, patient-reported outcomes, multi-morbidity, psychometric testing, questionnaire, validation

Guilherme S Lopes,1,2 Suzette J Bielinski,2 Ann M Moyer,3 John Logan Black III,3 Debra J Jacobson,1 Ruoxiang Jiang,1 Nicholas B Larson,1 Jennifer L St Sauver2 1Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USACorrespondence: Guilherme S LopesDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USATel +1 507 422 6094Email lopes.guilherme@mayo.eduBackground: Several small studies have previously investigated associations between the cytochrome P450 2D6 (CYP2D6) metabolism and response to opioids. We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use. We conducted additional analyses to determine whether our results were consistent among men and women.Methods: We used data from 2,877 participants in the RIGHT Protocol who were prescribed codeine and/or tramadol between 01/01/2005 and 12/31/2017 and who were not prescribed CYP2D6 inhibitors within 1 year prior to the opioid prescription. CYP2D6 phenotype categories were condensed into four groups: (1) Ultra-rapid and Rapid (n = 61), (2) Normal and Intermediate to Normal (n = 1,448), (3) Intermediate and Intermediate to Poor (n = 1,175), and (4) Poor metabolizer status (n = 193). Opioid-related outcomes included indications of poor pain control or adverse reactions related to medication use. We modeled the risk of each outcome using logistic regression, adjusting for age, sex, race, and ethnicity.Results: The results revealed a trend from poor to ultra-rapid and rapid CYP2D6 phenotypes in which the risk of adverse reactions incrementally increased and the risk of poor pain control incrementally decreased. This trend reached statistical significance among female (but not male) participants. Among normal and intermediate to normal metabolizers, a larger proportion of women experienced adverse reactions relative to men.Discussion: We replicated and extended the findings of previous research indicating associations between CYP2D6 phenotypes and response to opioids. In addition, the observed associations were stronger in women than in men. We recommend sex differences to be factored in future research investigating associations between pharmacogenomics and response to medications.Keywords: opioids, codeine, tramadol, pharmacogenomics, sex differences, CYP2D6

David T Eton,1,2 Jennifer L Ridgeway,1,2 Mark Linzer,3 Deborah H Boehm,4 Elizabeth A Rogers,5 Kathleen J Yost,1,2 Lila J Finney Rutten,1,2 Jennifer L St Sauver,1,2 Sara Poplau,4 Roger T Anderson6 1Department of Health Sciences Research, 2Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, 3Division of General Internal Medicine, Hennepin County Medical Center, 4Minneapolis Medical Research Foundation, 5Division of General Internal Medicine, University of Minnesota Medical School, Minneapolis, MN, 6Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA Purpose: Having multiple chronic conditions (MCCs) can lead to appreciable treatment and self-management burden. Healthcare provider relational quality (HPRQ) – the communicative and interpersonal skill of the provider – may mitigate treatment burden and promote self-management. The objectives of this study were to 1) identify the associations between HPRQ, treatment burden, and psychosocial outcomes in adults with MCCs, and 2) determine if certain indicators of HPRQ are more strongly associated than others with these outcomes.Patients and methods: This is a cross-sectional survey study of 332 people with MCCs. Patients completed a 7-item measure of HPRQ and measures of treatment and self-management burden, chronic condition distress, self-efficacy, provider satisfaction, medication adherence, and physical and mental health. Associations between HPRQ, treatment burden, and psychosocial outcomes were determined using correlational analyses and independent samples t-tests, which were repeated in item-level analyses to explore which indicators of HPRQ were most strongly associated with the outcomes.Results: Most respondents (69%) were diagnosed with ≥3 chronic conditions. Better HPRQ was found to be associated with less treatment and self-management burden and better psychosocial outcomes (P

Jennifer L St Sauver,1,2 Janet E Olson,1,3 Veronique L Roger,1,2,4 Wayne T Nicholson,5 John L Black III,3,6 Paul Y Takahashi,7 Pedro J Caraballo,7 Elizabeth J Bell,2 Debra J Jacobson,1,2 Nicholas B Larson,1 Suzette J Bielinski,1,3 1Department of Health Sciences Research, 2Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, 3Center for Individualized Medicine, 4Department of Cardiovascular Diseases, 5Department of Anesthesiology and Perioperative Medicine, 6Department of Laboratory Medicine and Pathology, 7Department of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN, USA Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients.Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression.Results: Overall, 257 (25% of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15%) were poor metabolizers, 146 (57%) were intermediate to extensive metabolizers, and 71 (28%) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003).Conclusion: Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial. Keywords: CYP2D6, opioid, phenotype, adverse effects

Paul Y Takahashi,1 Jennifer L St Sauver,2 Lila J Finney Rutten,2 Robert M Jacobson,3 Debra J Jacobson,2 Michaela E McGree,2 Jon O Ebbert1 1Department of Internal Medicine, Division of Primary Care Internal Medicine, 2Department of Health Sciences Research, Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, 3Department of Pediatric and Adolescent Medicine, Division of Community Pediatrics, Mayo Clinic, Rochester, MN, USA Objective: Our objective was to understand the relationship between optimal diabetes control, as defined by Minnesota Community Measurement (MCM), and adverse health outcomes including emergency department (ED) visits, hospitalizations, 30-day rehospitalization, intensive care unit (ICU) stay, and mortality. Patients and methods: In 2009, we conducted a retrospective cohort study of empaneled Employee and Community Health patients with diabetes mellitus. We followed patients from 1 September 2009 until 30 June 2011 for hospitalization and until 5 January 2014 for mortality. Optimal control of diabetes mellitus was defined as achieving the following three measures: low-density lipoprotein (LDL) cholesterol

Lila J Finney Rutten,1 Sana N Vieux,2 Jennifer L St Sauver,1 Neeraj K Arora,2 Richard P Moser,2 Ellen Burke Beckjord,3 Bradford W Hesse2 1Robert D. and Patricia E. Kern Center for the Science of Healthcare Delivery, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA; 3Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Purpose: Despite considerable potential for improving health care quality, adoption of new technologies, such as electronic medical records (EMRs), requires prudence, to ensure that such tools are designed, implemented, and used meaningfully to facilitate patient-centered communication and care processes, and better health outcomes. The association between patients’ perceptions of health care provider use of EMRs and health care quality ratings was assessed. Method: Data from two iterations of the Health Information National Trends Survey, fielded in 2011 and 2012, were pooled for these analyses. The data were collected via mailed questionnaire, using a nationally representative listing of home addresses as the sampling frame (n=7,390). All data were weighted to provide representative estimates of quality of care ratings and physician use of EMR, in the adult US population. Descriptive statistics, t-tests, and multivariable linear regression analyses were conducted. Results: EMR use was reported significantly more frequently by females, younger age groups, non-Hispanic whites, and those with higher education, higher incomes, health insurance, and a usual source of health care. Respondents who reported physician use of EMRs had significantly higher ratings of care quality (Beta=4.83, standard error [SE]=1.7, P

Paul Y Takahashi.1 Jennifer L St Sauver,2 Timothy C Olson,1 Jill M Huber,1 Stephen S Cha,2 Jon O Ebbert11Division of Primary Care Internal Medicine, 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USABackground: In older adults, underweight (body mass index [BMI] < 18.5) has been associated with increased mortality. This increased mortality risk may be associated with increased health care utilization. We evaluated the relationship between underweight and hospitalization, emergency room visits, and mortality.Methods: An analysis of a retrospective cohort study was conducted at a multisite academic primary care medical practice in Minnesota. The patients were ≥60 years of age, impaneled within primary care on January 1, 2011, and had a BMI measurement recorded between January 1, 2011, and December 31, 2011. Individuals were excluded if they refused review of their medical record. The primary measurement was BMI, which was categorized as underweight (BMI < 18.5) or normal and obese (BMI ≥ 18.5). The outcomes were hospitalization, emergency room visits, and mortality in the 2011 calendar year. Associations between underweight and each outcome were calculated using logistic regression. Interactions between underweight and gender were assessed in the logistic regression models. The final results were adjusted for age, gender, comorbid health conditions, and single living status.Results: The final cohort included 21,019 patients, of whom 220 (1%) were underweight. Underweight patients had a higher likelihood of hospitalization compared with patients with higher BMI (adjusted odds ratio [OR] 1.64; 95% confidence interval [CI] 1.21–2.22). Underweight patients were also more likely to visit the emergency room (adjusted OR 1.70; 95% CI 1.28–2.25) or to die (adjusted OR 3.64; 95% CI 2.33–5.69). Men with a BMI < 18.5 compared with those having a BMI ≥ 18.5 had the highest odds of hospitalization (OR 3.45; 95% CI 1.59–7.48).Conclusion: Underweight older adults, especially men, have higher odds of hospitalization, emergency room visits, and mortality. Future work on underweight might involve improving weight status, which may reduce the risk of hospitalization, emergency room visits, and mortality.Keywords: aging, health care utilization, nutrition, population health

Objective: To define the population-based 3-year period prevalence of repeated group A beta-hemolytic streptococcal (GABHS) pharyngitis episodes in children between 4 and 15 years of age.Patients and Methods: Residents of Rochester, Minn (age, 4-15 years), who had 3 or more GABHS pharyngitis episodes In 1 year, at least 1 month apart, between January 1, 1996, and December 31, 1998, were Identified using the resources of the Rochester Epidemiology Project (N=536). Pharyngitis episodes (evidence of a sore throat with or without presence of fever) followed by either a positive rapid streptococcus test result or a positive plate culture test result were considered positive GABHS episodes. Age- and sex-specific prevalence rates were calculated, assuming that all residents 4 to 15 years of age in Rochester during 1996 to 1998 were at risk.Results: A total of 208 children met our definition for repeated GABHS episodes between 1996 and 1998 and were included in this study. Approximately 1% of children between the ages of 4 and 15 years experienced repeated GABHS pharyngitis episodes between 1996 and 1998. This estimate increased to approximately 2% among children 4 to 6 years of age and decreased to 0.1% among children 13 to 15 years old.Conclusion: A relatively small proportion (1%) of children between 4 and 15 years of age experienced repeated GABHS episodes in a 3-year period; however, this proportion represents a substantial number of children who are affected at the population level. Given the increased costs associated with treating repeated GABHS episodes, further studies are necessary to determine how best to reduce episodes and treatment costs in this age group. [ABSTRACT FROM AUTHOR]

Objective: To determine how well patient-reported cardiovascular disease (CVD) and CVD risk factor information agrees with medical record information.Methods: Information from Patient/Family History (PFH) questionnaires completed between 1996 and 1999 by residents of Olmsted County, Minnesota, aged 20 years and older was compared with information available through the Mayo Clinic medical diagnostic index. Positive and negative agreement values were calculated by comparing agreement between the 2 data sources. Also, with the Mayo Medical Index serving as the criterion standard, sensitivity, specificity, and positive and negative predictive values of questionnaire information were calculated overall and by subgroups of sex, age, and years of education.Results: Questionnaire responses were retrieved for 26,162 patients. Positive agreement values ranged from 31% for report of a medical problem or surgery related to arteries to the head, arms, or legs or the aorta to 78% for high blood pressure. Negative agreement values ranged from 90% for high cholesterol to 98% for medical problem or surgery related to arteries to the head, arms, or legs or the aorta. Sensitivity of questionnaire information ranged from 37% to 73%, whereas positive predictive values ranged from 27% to 86%. Positive agreement, sensitivity, and positive predictive values tended to increase with increasing age of the patient. Specificity and negative predictive values were 87% or greater, and negative agreement, specificity, and negative predictive values decreased with increasing age.Conclusion: Positive patient reports of CVD conditions and risk factors are relatively inaccurate. However, negative self-reports of these conditions are unlikely to be noted in the medical record. Further development of the PFH questionnaire is necessary to ensure accurate patient reporting of CVD data. [ABSTRACT FROM AUTHOR]

Objectives: To Identify risk factors for attention-deficit/hyperactivity disorder (ADHD) and to determine whether these factors differ between boys and girls.Subjects and Methods: We conducted a case-control study of all children born between January 1, 1976, and December 31, 1982, in Olmsted County, Minnesota (N=5701), and examined birth certificates for risk factors for ADHD. Using school and medical records, we identified 305 children with ADHD. All children not identified with ADHD served as controls (N=5326). Risk factors that were assessed included demographic characteristics of both children and parents, as well as pregnancy, labor, and delivery characteristics, including the effect of a multiple birth and presence of pregnancy and delivery complications.Results: Pregnancy and labor characteristics, low birth weight, and presence of a twin birth were not associated with ADHD. Male sex (odds ratio [OR], 3.05; 95% confidence interval [CI], 2.34-3.98) was associated with an increased risk for ADHD, whereas high maternal and paternal education levels (high maternal education: OR, 0.57; 95% CI, 0.42-0.78; high paternal education: OR, 0.58; 95% CI, 0.49-0.78) were associated with a decreased risk for ADHD. In addition, low maternal and paternal education levels increased the risk for ADHD in boys more than in girls.Conclusion: Male sex and low parental education levels are significant risk factors for ADHD. In addition, boys born to parents with low maternal and paternal education levels appear to be at an increased risk for ADHD compared with girls born to parents with low education levels. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe and compare the incidence and clinical characteristics of tuberculosis in Olmsted County, Minnesota, among US-born and foreign-born persons. PATIENTS AND METHODS: We performed a retrospective cohort study at the Mayo Clinic in Rochester, Minn, of all residents of Olmsted County (2000 population: 124,277) diagnosed as having tuberculosis between January 1, 1990, and December 31, 2001. Potential cases were identified with use of a computerized diagnostic coding database and microbiological laboratory data; all identified medical records were abstracted. Definite cases were those in which Mycobacterium tuberculosis was recovered in culture. Probable cases were those that met predefined clinical or radiographic evidence of tuberculosis and other criteria. Age-specific, sex-specific, and country of origin-specific incidence rates were calculated with use of Olmsted County census data. Variables were compared among risk groups using the Fisher exact test. RESULTS: During a 12-year period, 71 cases of tuberculosis (53 definite, 18 probable) were identified, for an incidence of 5.3 per 100,000 person-years. Of these cases, 54 (76%) occurred during the second half of the study (incidence: 7.7 per 100,000 person-years). The incidence among US-born persons was similar throughout the study period; however, the Incidence among foreign-born persons increased more than 3-fold during the second half of the study period. Twenty-five patients (35%) were former refugees. All isoniazid-resistant infections (12% of isolates) and multidrug-resistant infections (6% of isolates) occurred among foreign-born persons. CONCLUSION: The incidence of tuberculosis increased substantially in Olmsted County between 1990 and 2001, primarily because of an increase in the number of cases among foreign-born persons. [ABSTRACT FROM AUTHOR]

Objective: To determine the longitudinal changes of benign prostate-specific antigen (BPSA) and [-2]proPSA and how these changes relate to the outcomes. These markers have been shown to be predictive of prostate cancer (CaP) and benign prostatic hyperplasia treatment; however, little is known about longitudinal changes in these markers.Methods: In 1990, a 25% subsample from a cohort of white men aged 40-79 years, who were randomly selected from Olmsted County, Minnesota residents, completed a detailed clinical examination. BPSA and [-2]proPSA were measured from frozen sera. The men were evaluated biennially (median follow-up 7 years; range 0-8.8). Mixed-effects regression models were used to estimate the longitudinal changes in the BPSA and [-2]proPSA levels overall and by outcomes. Spearman correlations were used to compare these changes with the baseline levels and the annualized changes in urologic measures.Results: The median and 25th and 75th percentiles annualized percent change for [-2]proPSA and BPSA was 3.7%, 2.5% and 5.2% and 7.3%, 6.8%, and 7.7%, respectively. The annualized percent change for both markers correlated with the baseline and annualized changes in PSA and prostate volume. The annualized percent change increased with increasing age decade for [-2]proPSA but not for BPSA. The rate of increase in [-2]proPSA was significantly greater for men who developed enlarged prostates (median 3.5%, 25th and 75th percentile 2.6% and 4.4%, respectively) or CaP (median 8.1%, 25th and 75th percentile 6.6% and 9.8%, respectively) compared with those who did not develop enlarged prostates (median 1.9%, 25th and 75th percentile 0.9% and 3.0%, respectively) or CaP (median 3.5%, 25th and 75th percentile 2.3% and 4.8%, respectively).Conclusion: BPSA and [-2]proPSA levels increase over time. The annualized percent change in [-2]proPSA increases with age and might be a useful predictor of CaP development. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between alpha-blocker use and sexual dysfunction among men participating in a population-based cohort of men residing in Olmsted County, MN. Lower urinary tract symptoms (LUTS) in men have previously been associated with sexual dysfunction. The use of alpha-adrenergic receptor blocking agents results in an improvement in LUTS for many men. If sexual dysfunction and LUTS share a common etiology, alpha-blocker use might also be associated with a decreased risk of sexual dysfunction.Methods: White men, aged 40-79 years, were randomly selected in 1990 and assessed for alpha-blocker use and LUTS severity. Sexual function was assessed using the Brief Male Sexual Function Inventory. Men who used alpha-blockers before any sexual dysfunction were considered "exposed." Hazard ratios and 95% confidence intervals were estimated separately for each sexual function domain using Cox proportional hazard models.Results: Of the 1724 men with a regular sexual partner included in the present study (mean age 57.74 years), 263 (15.3%) reported alpha-blocker use. alpha-Blocker use was associated with a decreased risk of sexual dysfunction across all domains for men > or =50 years old (age-adjusted hazard ratio 0.53-0.69). A decreased risk of erectile dysfunction and low libido remained significant only among those using alpha-blockers who also experienced an improvement in LUTS (P = .01).Conclusions: The use of alpha-blockers for LUTS was associated with a decreased risk of sexual dysfunction. Improvement in sexual function correlated with the improvement in LUTS more strongly among those using alpha-blockers. [ABSTRACT FROM AUTHOR]

Objective: To determine the risk of congenital cardiac abnormalities associated with use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy.Patients and Methods: We conducted a retrospective review of the medical records of all pregnant women presenting at Mayo Clinic's site in Rochester, MN, from January 1, 1993, to July 15, 2005, and identified 25,214 deliveries. A total of 808 mothers were treated with SSRIs at some point during their pregnancy. We reviewed the medical records of the newborns exposed to SSRIs during pregnancy to analyze their outcomes, specifically for congenital heart disease and persistent pulmonary hypertension of the newborn.Results: Of the study patients, 808 (3.2%) took an SSRI at some point during the antenatal period. Of the 25,214 deliveries, 208 newborns (0.8%) were diagnosed as having congenital heart disease. Of the 808 women exposed to SSRI during pregnancy, 3 (0.4%) had congenital heart disease compared with 205 (0.8%) of the 24,406 women not exposed to an SSRI (P=.23). Of the total number of deliveries, 16 newborns were diagnosed as having persistent pulmonary hypertension of the newborn, none of whom had exposure to SSRIs (P>.99).Conclusion: Our data are reassuring regarding the safety of using SSRIs during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity.Patients and Methods: We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined.Results: During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01).Conclusion: This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span. [ABSTRACT FROM AUTHOR]

Objective: To establish accurate, up-to-date, baseline epidemiological data for herpes zoster (HZ) before the introduction of the recently licensed HZ vaccine.Methods: Using data from January 1, 1996, to October 15, 2005, we conducted a population-based study of adult residents (Greater than or equal to 22 years) of Olmsted County, MN, to determine (by medical record review) the incidence of HZ and the rate of HZ-related complications. Incidence rates were determined by age and sex and adjusted to the US population.Results: A total of 1669 adult residents with a confirmed diagnosis of HZ were identified between January 1, 1996, and December 31, 2001. Most (92%) of these patients were immunocompetent and 60% were women. When adjusted to the US adult population, the incidence of HZ was 3.6 per 1000 person-years (95% confidence interval, 3.4-3.7), with a temporal increase from 3.2 to 4.1 per 1000 person-years from 1996 to 2001. The incidence of HZ and the rate of HZ-associated complications increased with age, with 68% of cases occurring in those aged 50 years and older. Postherpetic neuralgia occurred in 18% of adult patients with HZ and in 33% of those aged 79 years and older. Overall, 10% of all patients with HZ experienced 1 or more nonpain complications.Conclusions: Our population-based data suggest that HZ primarily affects immunocompetent adults older than 50 years; 1 in 4 experiences some type of HZ-related complication. [ABSTRACT FROM AUTHOR]

Objective: Infectious mononucleosis (IM) or mono is typically caused by primary infection with Epstein-Barr virus (EBV) and may have a months-long, complicated course. We utilized population-based data to add to the limited literature on health care utilization following EBV infection., Methods: The Rochester Epidemiology Project includes medical records for ∼60% of residents living in 27 counties of Minnesota (MN) and Wisconsin (WI). Persons meeting a case definition of recent EBV infection from 1 January 1998 to 31 December 2021 were compared to three persons not meeting the definition, matched on case's sex, age, and index date. Emergency department (ED) visits and hospitalizations in the two groups were compared during 5-years' follow-up divided into three periods (short-term ≤3 months, mid-term >3 months-1 year, long-term >1-5 years). Adjusted hazard ratios (AHR) were estimated to account for the potential influence of confounding variables., Results: In total, 6,423 persons had a recent EBV infection and were matched to 19,269 comparators. The risk of an ED visit was significantly higher among cases in the short-term period (24.3% vs referents: 7.6%, p  <.001; AHR = 3.71, 95% CI = 3.41-4.03). Cases also had an increased risk of hospitalization in the short-term (5.2% vs 1.6%: referents, p  <.001; AHR = 3.53, 95% CI = 2.94-4.24). For ED visits but not hospitalization, the excess risk persisted into the mid-term follow-up period. Persons without a concurrent clinical diagnosis of IM continued to have an increased risk of hospitalizations up to 1 year after index date (AHR = 1.45, 95% CI = 1.09-1.91) and an increased risk of ED visits up to 5 years after the index date (AHR = 1.29, 95% CI = 1.14-1.46)., Conclusion: There is a substantial short- and mid-term increased risk of serious health care encounters associated with recent EBV infection. Mid- and long-term risks are increased in patients who do not have a concomitant diagnosis of IM.

People living with dementia have high rates of hospitalizations. Identifying factors that influence hospitalization is important. This study examines the influence of physical activity levels on risk of hospitalization and emergency department (ED) use among older people living with mild cognitive impairment (MCI) or dementia followed in our primary care practice in Rochester, Minnesota, United States. We included those age 55 years and older, who had a clinic visit between June 1, 2019 and June 30, 2021 and completed a social determinants of health questionnaire about physical activity levels ( n = 3090). Physical activity was classified as sufficiently active, insufficiently active, or physically inactive. Risk of hospitalization and ED visits by physical activity levels were examined. People who were physically inactive were at higher risk of hospitalization and ED visits ( p < .001) compared with those who were sufficiently active. This highlights an area for health promotion in people living with MCI and dementia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: An abstract containing some of this data has been submitted to the Alzheimer’s Association International Conference, July 2024.

Background and Objectives: Social isolation is commonly experienced by older people and is associated with adverse health outcomes. Little is known about the influence of social isolation on the risk of acute care utilization among people living with mild cognitive impairment (MCI) or dementia. Our objective was to investigate the impact of social isolation on the risk of death, hospitalization, and emergency department (ED) use among people living with MCI or dementia who are followed in our Community Internal Medicine practice at Mayo Clinic, Rochester, Minnesota., Research Design and Methods: We included people living with MCI or dementia, 55 years and older, who had a clinic visit between June 1, 2019, and June 30, 2021, and who had completed questions about social connections. The risk of death, hospitalization, and ED use was examined by levels of social connection (socially isolated, moderately isolated, moderately integrated, or socially integrated)., Results: Of 2,320 people included (1,010 with MCI and 1,310 with dementia), 455 (19.6%) were classified as socially isolated and 591 (25.5%) were moderately isolated. Compared with those who were socially integrated, people who were socially isolated were at higher risk of death, hospitalization, and ED visits ( p  < .001)., Discussion and Implications: Social isolation is associated with an increased risk of acute health care utilization and death in people living with MCI or dementia. Interventions to address social isolation in this population are needed., Competing Interests: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objective: To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial., Design: Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported., Results: During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals., Conclusions: Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data., Trial Registration Number: NCT04124406., Competing Interests: Competing interests: KJY, REC, CRK, EJK, JLSS, JAG and JEO are employees of Mayo Clinic and received funding for this study through a grant from Exact Sciences Corporation. BK and JJL are employees and shareholders of Exact Sciences. At the start of the work herein, LJFR was an employee of the Mayo Clinic, whereby she offered scientific input to Exact Sciences for research studies through a contracted services agreement between Mayo Clinic and Exact Sciences Corporation. During the writing of this manuscript, she became a full-time employee of Exact Sciences Corporation. Currently, she is an employee of Mayo Clinic only., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether body composition derived from medical imaging may be useful for assessing biologic age at the tissue level because people of the same chronologic age may vary with respect to their biologic age., Methods: We identified an age- and sex-stratified cohort of 4900 persons with an abdominal computed tomography scan from January 1, 2010, to December 31, 2020, who were 20 to 89 years old and representative of the general population in Southeast Minnesota and West Central Wisconsin. We constructed a model for estimating tissue age that included 6 body composition biomarkers calculated from abdominal computed tomography using a previously validated deep learning model., Results: Older tissue age associated with intermediate subcutaneous fat area, higher visceral fat area, lower muscle area, lower muscle density, higher bone area, and lower bone density. A tissue age older than chronologic age was associated with chronic conditions that result in reduced physical fitness (including chronic obstructive pulmonary disease, arthritis, cardiovascular disease, and behavioral disorders). Furthermore, a tissue age older than chronologic age was associated with an increased risk of death (hazard ratio, 1.56; 95% CI, 1.33 to 1.84) that was independent of demographic characteristics, county of residency, education, body mass index, and baseline chronic conditions., Conclusion: Imaging-based body composition measures may be useful in understanding the biologic processes underlying accelerated aging., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population., Methods: We identified a population-representative sample of 4 900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section., Results: We report CT-based body composition reference ranges on 4 649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density., Conclusions: We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4 649 persons by age, sex, body mass index, and chronic conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

National or statewide estimates of excess deaths have limited value to understanding the impact of the COVID-19 pandemic regionally. We assessed excess deaths in a 9-county geographically defined population that had low rates of COVID-19 and widescale availability of testing early in the pandemic, well-annotated clinical data, and coverage by 2 medical examiner's offices. We compared mortality rates (MRs) per 100,000 person-years in 2020 and 2021 with those in the 2019 reference period and MR ratios (MRRs). In 2020 and 2021, 177 and 219 deaths, respectively, were attributed to COVID-19 (MR = 52 and 66 per 100,000 person-years, respectively). COVID-19 MRs were highest in males, older persons, those living in rural areas, and those with 7 or more chronic conditions. Compared with 2019, we observed a 10% excess death rate in 2020 (MRR = 1.10 [95% CI, 1.04 to 1.15]), with excess deaths in females, older adults, and those with 7 or more chronic conditions. In contrast, we did not observe excess deaths overall in 2021 compared with 2019 (MRR = 1.04 [95% CI, 0.99 to 1.10]). However, those aged 18 to 39 years (MRR = 1.36 [95% CI, 1.03 to 1.80) and those with 0 or 1 chronic condition (MRR = 1.28 [95% CI, 1.05 to 1.56]) or 7 or more chronic conditions (MRR = 1.09 [95% CI, 1.03 to 1.15]) had increased mortality compared with 2019. This work highlights the value of leveraging regional populations that experienced a similar pandemic wave timeline, mitigation strategies, testing availability, and data quality., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Importance: Despite availability of a safe and effective vaccine, an estimated 36 500 new cancers in the US result from human papillomavirus (HPV) annually. HPV vaccine uptake falls short of national public health goals and lags other adolescent vaccines., Objective: To evaluate the individual and combined impact of 2 evidence-based interventions on HPV vaccination rates among 11- and 12-year-old children., Design, Setting, and Participants: The study team conducted a cluster randomized clinical trial with a stepped-wedge factorial design at 6 primary care practices affiliated with Mayo Clinic in southeastern Minnesota. Using block randomization to ensure balance of patient volumes across interventions, each practice was allocated to a sequence of four 12-month steps with the initial baseline step followed by 2 intermediate steps (none, 1, or both interventions) and a final step wherein all practices implemented both interventions. Each month, all eligible children who turned 11 or 12 years in the 2 months prior were identified and followed until the end of the step. Data were analyzed from April 2018 through March 2019. Participants included children who turned 11 or 12 years old and were due for a dose of the HPV vaccine., Interventions: Parents of eligible patients were mailed reminder/recalls following their child's birthdays. Health care professionals received confidential audit/feedback on their personal in-office success with HPV vaccine uptake via intra-campus mail. These 2 interventions were assessed separately and in combination., Main Outcomes and Measures: Eligible patients' receipt of any valid dose of HPV vaccine during the study step., Results: The cohort was comprised of 9242 11-year-olds (5165 [55.9%]) and 12-year-olds (4077 [44.1%]), and slightly more males (4848 [52.5%]). Parent reminder/recall resulted in 34.6% receiving a dose of HPV vaccine, health care professional audit/feedback, 30.4%, both interventions together resulted in 39.7%-all contrasted to usual care, 21.9%. Compared with usual care, the odds of HPV vaccination were higher for parent reminder/recall (odds ratio [OR], 1.56; 95% CI, 1.23-1.97) and for the combination of parent reminder/recall and health care professional audit/feedback (OR, 2.03; 95% CI, 1.44-2.85). Health care professional audit/feedback alone did not differ significantly from usual care (OR, 1.19; 95% CI, 0.94-1.51)., Conclusions and Relevance: In this cluster randomized trial, the combination of parent reminder/recall and health care professional audit/feedback increased the odds of HPV vaccination compared with usual care. These findings underscore the value of simultaneous implementation of evidence-based strategies to improve HPV vaccination.

Background: Physical activity can improve physical health for people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is needed. We sought to examine the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia., Methods: This descriptive study included people with a diagnosis of MCI or dementia followed by Community Internal Medicine at Mayo Clinic (Rochester, Minnesota, United States), aged over 55 years, who had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity, and transportation needs. Data were analyzed based on physical activity level (inactive, insufficiently active, sufficiently active). SDOH domains were compared according to physical activity level using the χ2 test and multinomial logistic regression., Results: A total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, screening positive for depression and increased social isolation (p < 0.001)., Conclusions: Physical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many factors, highlighting potential areas for intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. The data was presented as an abstract at the Alzheimer's Association International Conference, Amsterdam, July 16–20, 2023., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators of age-related pathology, components of the senescence associated secretory phenotype (SASP) have been studied as biomarkers of senescent cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations of candidate senescence biomarkers, including chemokines, cytokines, matrix remodeling proteins, and growth factors, could predict mortality in older adults. We assessed associations between plasma levels of 28 SASP proteins and risk of mortality over a median follow-up of 6.3 years in 1923 patients 65 years of age or older with zero or one chronic condition at baseline. Overall, the five senescence biomarkers most strongly associated with an increased risk of death were GDF15, RAGE, VEGFA, PARC, and MMP2, after adjusting for age, sex, race, and the presence of one chronic condition. The combination of biomarkers and clinical and demographic covariates exhibited a significantly higher c-statistic for risk of death (0.79, 95% confidence interval (CI): 0.76-0.82) than the covariates alone (0.70, CI: 0.67-0.74) (p < 0.001). Collectively, these findings lend further support to biomarkers of cellular senescence as informative predictors of clinically important health outcomes in older adults, including death., (© 2023 Mayo Clinic. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background and Objectives: Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD., Methods: All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD., Results: The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk., Discussion: In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare the 1-year health care utilization and mortality in persons living with heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic., Patients and Methods: Residents of a 9-county area in southeastern Minnesota aged 18 years or older with a HF diagnosis on January 1, 2019; January 1, 2020; and January 1, 2021, were identified and followed up for 1-year for vital status, emergency department (ED) visits, and hospitalizations., Results: We identified 5631 patients with HF (mean age, 76 years; 53% men) on January 1, 2019, 5996 patients (mean age, 76 years; 52% men) on January 1, 2020, and 6162 patients (mean age, 75 years; 54% men) on January 1, 2021. After adjustment for comorbidities and risk factors, patients with HF in 2020 and patients with HF in 2021 experienced similar risks of mortality compared with those in 2019. After adjustment, patients with HF in 2020 and 2021 were less likely to experience all-cause hospitalizations (2020: rate ratio [RR], 0.88; 95% CI, 0.81-0.95; 2021: RR, 0.90; 95% CI, 0.83-0.97) compared with patients in 2019. Patients with HF in 2020 were also less likely to experience ED visits (RR, 0.85; 95% CI, 0.80-0.92)., Conclusion: In this large population-based study in southeastern Minnesota, we observed an approximately 10% decrease in hospitalizations among patients with HF in 2020 and 2021 and a 15% decrease in ED visits in 2020 compared with those in 2019. Despite the change in health care utilization, we found no difference in the 1-year mortality between patients with HF in 2020 and those in 2021 compared with those in 2019. It is unknown whether any longer-term consequences will be observed., Competing Interests: Given his role as an Editorial Board Member, Dr Paul Takahashi, was not involved in the peer-review of this article and had no access to information regarding its peer-review. All other authors report no potential competing interests., (© 2023 The Authors.)

Objective: Ceramides have been associated with several ageing-related conditions but have not been studied as a general biomarker of multimorbidity (MM). Therefore, we determined whether ceramide levels are associated with the rapid development of MM., Design: Retrospective cohort study., Setting: Mayo Clinic Biobank., Participants: 1809 persons in the Mayo Clinic Biobank ≥65 years without MM at the time of enrolment, and with ceramide levels assayed from stored plasma., Primary Outcome Measure: Persons were followed for a median of 5.7 years through their medical records to identify new diagnoses of 20 chronic conditions. The number of new conditions was divided by the person-years of follow-up to calculate the rate of accumulation of new chronic conditions., Results: Higher levels of C18:0 and C20:0 were associated with a more rapid rate of accumulation of chronic conditions (C18:0 z score RR: 1.30, 95% CI: 1.10 to 1.53; C20:0 z score RR: 1.26, 95% CI: 1.07 to 1.49). Higher C18:0 and C20:0 levels were also associated with an increased risk of hypertension and coronary artery disease., Conclusions: C18:0 and C20:0 were associated with an increased risk of cardiometabolic conditions. When combined with biomarkers specific to other diseases of ageing, these ceramides may be a useful component of a biomarker panel for predicting accelerated ageing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : The Rochester Epidemiology Project (REP) medical records-linkage system offers a unique opportunity to integrate medical and residency data with existing environmental data, to estimate individual-level exposures. Our primary aim was to provide an archetype of this integration. Our secondary aim was to explore the association between groundwater inorganic nitrogen concentration and adverse child and adolescent health outcomes. Methods : We conducted a nested case-control study in children, aged seven to eighteen, from six counties of southeastern Minnesota. Groundwater inorganic nitrogen concentration data were interpolated, to estimate exposure across our study region. Residency data were then overlaid, to estimate individual-level exposure for our entire study population ( n = 29,270). Clinical classification software sets of diagnostic codes were used to determine the presence of 21 clinical conditions. Regression models were adjusted for age, sex, race, and rurality. Results : The analyses support further investigation of associations between nitrogen concentration and chronic obstructive pulmonary disease and bronchiectasis (OR: 2.38, CI: 1.64-3.46) among boys and girls, thyroid disorders (OR: 1.44, CI: 1.05-1.99) and suicide and intentional self-inflicted injury (OR: 1.37, CI: >1.00-1.87) among girls, and attention deficit conduct and disruptive behavior disorders (OR: 1.34, CI: 1.24-1.46) among boys. Conclusions : Investigators with environmental health research questions should leverage the well-enumerated population and residency data in the REP.

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.

Objectives: Obesity is a potentially modifiable risk factor that has been consistently associated with the development and progression of multi-morbidity (MM). However, obesity may be more problematic for some persons compared to others because of interactions with other risk factors. Therefore, we studied the effect of interactions between patient characteristics and overweight and obesity on the rate of accumulation of MM., Methods: We studied 4 cohorts of persons ages 20-, 40-, 60-, and 80-years residing in Olmsted County, Minnesota between 2005 and 2014 using the Rochester Epidemiology Project (REP) medical records-linkage system. Body mass index, sex, race, ethnicity, education, and smoking status were extracted from REP indices. The rate of accumulation of MM was calculated as the number of new chronic conditions accumulated per 10 person years through 2017. Poisson rate regression models were used to identify associations between characteristics and rate of MM accumulation. Additive interactions were summarized using relative excess risk due to interaction, attributable proportion of disease, and the synergy index., Results: Greater than additive synergistic associations were observed between female sex and obesity in the 20- and 40-year cohorts, between low education and obesity in the 20-year cohort (both sexes), and between smoking and obesity in the 40-year cohort (both sexes)., Conclusions: Interventions targeted at women, persons with lower education, and smokers who also have obesity may result in the greatest reduction in the rate of MM accumulation. However, interventions may need to focus on persons prior to mid-life to have the greatest effect., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objectives: To compare the agreement between percentile ranks from 4 multi-morbidity scores., Design: Population-based descriptive study., Setting: Olmsted County, Minnesota (USA)., Participants: We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years)., Methods: For each person, we calculated 4 multi-morbidity scores using readily available diagnostic code lists from the US Department of Health and Human Services, the Clinical Classifications Software, and the Elixhauser Comorbidity Index. We calculated scores using diagnostic codes received in the 5 years before the index birthday and fit quantile regression models across age and separately by sex to transform unweighted, simple counts of conditions into percentile ranks as compared to peers of same age and of same sex. We compared the percentile ranks of the 4 multi-morbidity scores using intra-class correlation coefficients (ICCs)., Results: We assessed agreement in 181,553 persons who reached a total of 1,075,433 birthdays at ages 18 years through 85 years during the study period. In general, the percentile ranks of the 4 multi-morbidity scores exhibited high levels of agreement in 6 score-to-score pairwise comparisons. The agreement increased with older age for all pairwise comparisons, and ICCs were consistently greater than 0.65 at ages 50 years and older., Conclusions: The assignment of percentile ranks may be a simple and intuitive way to assess the underlying trait of multi-morbidity across studies that use different measures., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Social determinants of health (SDOH) may influence health in people living with dementia. Little is known about SDOH differences in urban compared to rural dwelling people living with dementia., Objectives: To explore urban-rural differences in SDOH in people living with mild cognitive impairment (MCI) and dementia., Design: Descriptive study., Setting/participants: People ≥55 years with MCI or dementia empaneled to Community Internal Medicine at Mayo Clinic (Rochester, MN, USA) who completed SDOH questions between June 1, 2019 and June 30, 2021 were included., Measurements: SDOH questions addressed education, depression, alcohol use, financial strain, food insecurity, physical activity, social connections, stress and transportation. SDOH data were compared by location based on Rural-Urban Commuting Areas Codes., Results: Of 3552 persons with MCI (n=1495) or dementia (n=2057), 62% lived in urban areas, 19% in large rural, 10% in small rural and 9% in isolated areas. Approximately 60% were physically inactive, 20% socially isolated and 30% had stress concerns. Rural patients experienced greater financial strain (p=0.003)., Conclusion: Social isolation, stress and physical inactivity are common in people living with MCI and dementia across urban and rural areas. Targeted interventions to improve physical and psychosocial health could have great impact in this population., Competing Interests: All authors declare no conflict of interest.

Objective: The purpose of this study was to compare prenatal characteristics and postpartum outcomes among Somali and non-Somali women residing in Olmsted County., Methods: We reviewed the medical records for a cohort of Somali women (≥18 years old; N= 298) who had singleton births between January 2009 and December 2014 and for an age-matched non-Somali cohort (N= 298) of women residing in Olmsted County, Minnesota. Logistic regression models which accounted for repeated measures were used to assess differences in prenatal and postpartum outcomes between Somali and non-Somali women., Results: Somali women had a significantly higher odds of cesarean section (adjusted OR=1.81; 95% CI=1.15, 2.84). Additionally, Somali women had a significantly lower odds of postpartum depression (adjusted OR=0.27; 95% CI=0.12, 0.63)., Conclusion: The reported adverse postpartum outcomes have implications for interventions aimed at addressing perinatal care disparity gaps for Somali women immigrant and refugee populations., (© 2021. W. Montague Cobb-NMA Health Institute.)

Introduction: End-of-life care differs by serious illness diagnosis. Cancer and dementia are serious illnesses that have been associated with less intensive end-of-life health care use. It is not known how health care utilization varies in the presence of >1 serious illness., Methods: We used the Rochester Epidemiology Project to identify persons living in a midwestern area who died on July 1, 2017-June 30, 2018 at age ≥65 years, and were seriously ill. We examined the number of emergency department (ED), hospital, and intensive care unit (ICU) stays in the last 6 months and the last 30 days of life. We used Poisson regression to determine the incidence rate ratio for ED, hospital, and ICU stay in the last 6 months and 30 days of life by number of serious illness diagnoses. For cancer and dementia, we examined the effect of an additional serious illness., Results: We included a population of 1372 adults who were, on average, 84 years, 52% female, and 96% white. Approximately 41% had multiple serious illnesses. Compared to older adults with 1 serious illness diagnosis, rates of hospitalization, and ICU stay for adults with 2 or ≥3 serious illness diagnoses were at least 1.5 times higher in the last 6 months and the last 30 days of life. Rates of ED visits were significantly higher for older adults with 2 or ≥3 serious illness diagnoses in the last 6 months of life, but only higher for those with ≥3 versus 1 serious illness diagnosis in the last 30 days of life. For both cancer and dementia, rates of ED visits, hospitalization and ICU stay were lower for the condition alone than when an additional serious illness diagnosis was present., Conclusion: Having multiple serious illnesses increases the risk of health care utilization at the end of life., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Persons who accumulate chronic conditions at a rate faster than their peers may experience accelerated aging and poor health outcomes, including functional limitations., Methods: Adults aged ≥40 years who resided in Olmsted County, Minnesota on 1 January 2006 were identified. The prevalence of 21 chronic conditions was ascertained, and age-specific quartiles of the number of chronic conditions was estimated within 4 age groups: 40-54, 55-64, 65-74, and ≥75 years. Difficulty with nine patient-reported functional limitations (including basic and instrumental activities of daily living and mobility activities) were ascertained through 31 October 2018. Cox regression was used to model associations of chronic condition quartiles with new-onset functional limitations considered separately. We estimated absolute risk differences and hazard ratios stratified by age group, and adjusted for sex, race, ethnicity, marital status, education, and the residual effect of age., Results: Among 39,624 persons (44.5% men, 93.2% white), the most common reported new functional limitations were difficulty with climbing stairs, walking, and housekeeping. For all functional limitations, the absolute risk differences were largest among the oldest age group (≥75 years). Approximately twofold increased hazard ratios were observed among those in the highest vs. lowest quartile for the three oldest age groups, and approximately threefold or higher hazard ratios were observed for persons aged 40-54 years., Conclusion: Persons with increased accumulation of chronic conditions experience increased risks of developing functional limitations compared to their peers. These findings underscore the importance of assessing health status and of employing interventions to prevent and effectively manage multi-morbidity at all ages., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)