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Background and ObjectivesStudies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life.MethodsParticipants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record–abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined.ResultsOf the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (allp< 0.05) in age- and education-adjusted models. There was an interaction (p= 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = −0.42,p< 0.001) vs 12 + years (b = −0.11,p= 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = −0.04,p< 0.001), language (beta = −0.03,p= 0.001), and attention (beta = −0.04,p< 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, andAPOEdid not attenuate results.DiscussionWomen with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

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 of1 serious illness.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.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.Having multiple serious illnesses increases the risk of health care utilization at the end of life.

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.

OBJECTIVE: To determine the association of socioeconomic status at the census block group level with chronic conditions, and to determine whether the associations differ by age, sex, race, or ethnicity. PATIENTS AND METHODS: Adults aged ≥20 years on April 1, 2015 from 7 counties in Southern Minnesota were identified using the Rochester Epidemiology Project records-linkage system. We estimated the prevalence of 19 chronic conditions (7 cardiometabolic, 7 other somatic, and 5 mental health conditions) at the individual level, and a composite measure of neighborhood socioeconomic disadvantage (the area deprivation index; ADI) at the census block group level (n=249). RESULTS: Among the 197,578 persons in our study, 46.7% were male, 49.5% were aged ≥50 years, 12.3% were of non-White race, and 5.3% were Hispanic. The risk of most chronic conditions increased with increasing ADI. For each cardiometabolic condition and most other somatic and mental health conditions, the pattern of increasing risk across ADI quintiles was attenuated, or there was no association across quintiles of ADI in the oldest age group (ages ≥70 years). Stronger associations between ADI and several cardiometabolic, other somatic, and mental health conditions were observed in women. CONCLUSION: Higher ADI was associated with increased risk of most chronic conditions, with more pronounced associations in younger persons. For some chronic conditions, the associations were stronger in women. Our findings underscore the importance of recognizing the overall and potentially differential impact of area-level deprivation on chronic disease outcomes for diverse populations.

There is increasing evidence that sex hormones may impact the development of obstructive lung disease (OLD). Therefore, we studied the effect of bilateral oophorectomy (oophorectomy) on the development of OLD. Women were identified from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Data were collected using the Rochester Epidemiology Project records-linkage system. A total of 1653 women who underwent oophorectomy and 1653 referent women of similar age were assessed for OLD using diagnostic codes and medical record abstraction. Women who underwent oophorectomy had an overall higher risk of all OLD, all chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis but not of all asthma, confirmed asthma, or confirmed COPD. The association with all OLD was stronger in women who were age ≤45 years at oophorectomy, never smokers, non-obese, and in women with benign indications; however, the interactions were not statistically significant. There was an increased risk of all asthma in women age ≤45 years at oophorectomy who took estrogen therapy. Never smokers of all ages had a stronger association of oophorectomy with all asthma and all COPD, whereas smokers had a stronger association of oophorectomy with emphysema and chronic bronchitis. Non-obese women of all ages had a stronger association of oophorectomy with all COPD, emphysema, and chronic bronchitis. The results of this study combined with the increased risk of several chronic diseases reported in previous studies suggest that oophorectomy in premenopausal women should be avoided unless there is clear evidence of a high genetic risk of ovarian cancer.

ImportanceThe association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial.ObjectiveTo assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy.Design, Setting, and ParticipantsThis cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records–linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups.ExposuresMedical record documentation of bilateral oophorectomy abstracted from a medical records–linkage system (Rochester Epidemiology Project).Main Outcomes and MeasuresIncidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review.ResultsAmong 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant.Conclusions and RelevanceIn this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.

To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the prevaccination era.We screened first responders (n=191) and Olmsted County employees (n=564) for antibodies to SARS-CoV-2 from November 1, 2020 to February 28, 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all polymerase chain reaction (PCR)-confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, abstracted symptom information, estimated rates of asymptomatic infection and examined related factors.Twenty (10.5%; 95% CI, 6.9%-15.6%) first responders and 38 (6.7%; 95% CI, 5.0%-9.1%) county employees had positive antibodies; an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4 of 20 (20%; 95% CI, 3.0%-37.0%) first responders and 10 of 39 (26%; 95% CI, 12.6%-40.0%) county employees were asymptomatic. Of 6020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385; 95% CI, 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age (0-18 years [odds ratio {OR}, 2.3; 95% CI, 1.7-3.1] and65 years [OR, 1.40; 95% CI, 1.0-2.0] compared with ages 19-44 years), body mass index (overweight [OR, 0.58; 95% CI, 0.44-0.77] or obese [OR, 0.48; 95% CI, 0.57-0.62] compared with normal or underweight) and tests after November 20, 2020 ([OR, 1.35; 95% CI, 1.13-1.71] compared with prior dates).Asymptomatic rates in Olmsted County before COVID-19 vaccine rollout ranged from 6% to 25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection.

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.

OBJECTIVE: The incidence of carpal tunnel syndrome (CTS) is higher in women, and peaks around the age of menopause. Therefore, we investigated whether bilateral oophorectomy is associated with an increased risk of severe CTS. METHODS: We included all of the 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication between 1988 and 2007, and a random sample of 1,653 age-matched referent women who did not undergo bilateral oophorectomy in Olmsted County, Minnesota. Diagnoses of CTS assigned to women over their entire lifetime were identified in these two cohorts. The risk of de novo severe CTS after bilateral oophorectomy (or index date) was evaluated using Cox proportional hazards models adjusted for potential confounders. RESULTS: Bilateral oophorectomy was associated with an increased risk of severe CTS (adjusted hazard ratio 1.65, 95% confidence interval 1.20-2.25). The risk was suggestively greater in women with lower body mass index, nulliparity, and with a benign ovarian indication for oophorectomy (non-significant interactions). We did not observe a protective effect of estrogen therapy after the oophorectomy. The findings were similar in secondary analyses considering the incidence of CTS of any severity or idiopathic CTS. CONCLUSIONS: The risk of severe CTS, common in perimenopausal women, is increased after bilateral oophorectomy. The association may be causal or due to confounding. Therefore, the precise biological mechanisms explaining the association and the absence of a mitigating effect of estrogen therapy should be further investigated.

OBJECTIVERecent population-based and hospital cohort studies have reported a decreasing incidence of aneurysmal subarachnoid hemorrhage (aSAH) and declining aSAH-associated case-fatality rates. Principal drivers of these trends are debated, but improvements in smoking cessation and hypertension control may be critical factors.METHODSThe population-based medical records linkage system of the Rochester Epidemiological Project was used to document aSAH incidence and 30-day case fatality rates during a 20-year study period (1996–2016) in Olmsted County, Minnesota. Incidence rates in the study period were compared with data from a previous Olmsted County study concerning aSAH incidence from 1965 to 1995 and with regional trends in tobacco use.RESULTSOne hundred nineteen incident cases of aSAH were included. The median age at hemorrhage was 59 years (range 16–94 years), and 74 patients were female (62.2%). The overall average annual aSAH incidence rate was 4.2/100,000 person-years (P-Y). The aSAH incidence rate decreased from 5.7/100,000 in 1996 to 3.5/100,000 P-Y in 2011–2016. The overall aSAH-associated 30-day case-fatality rate was 21.9% and declined by approximately 0.5% annually. An accelerated decline in the fatality rate (0.9%/year) was observed from 2006–2016. Smoking among adult Olmsted County residents decreased from 20.4% in 2000 to 9.1% in 2018.CONCLUSIONSA decline in the incidence of aSAH and 30-day case-fatality rate from 1996 to 2016 was observed, as well as an accelerated decline of the fatality rate from 2006 to 2016. These findings confirm and extend the trends reported by prior studies in the same population. The decrease in aSAH in the years studied paralleled a noticeable reduction in the population smoking rates.

Background Delirium is underdiagnosed in clinical practice and is not routinely coded for billing. Manual chart review can be used to identify the occurrence of delirium; however, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) has the capability to process raw text in electronic health records (EHRs) and determine the meaning of the information. We developed and validated NLP algorithms to automatically identify the occurrence of delirium from EHRs. Methods This study used a randomly selected cohort from the population-based Mayo Clinic Biobank (N = 300, age ≥65). We adopted the standardized evidence-based framework confusion assessment method (CAM) to develop and evaluate NLP algorithms to identify the occurrence of delirium using clinical notes in EHRs. Two NLP algorithms were developed based on CAM criteria: one based on the original CAM (NLP-CAM; delirium vs no delirium) and another based on our modified CAM (NLP-mCAM; definite, possible, and no delirium). The sensitivity, specificity, and accuracy were used for concordance in delirium status between NLP algorithms and manual chart review as the gold standard. The prevalence of delirium cases was examined using International Classification of Diseases, 9th Revision (ICD-9), NLP-CAM, and NLP-mCAM. Results NLP-CAM demonstrated a sensitivity, specificity, and accuracy of 0.919, 1.000, and 0.967, respectively. NLP-mCAM demonstrated sensitivity, specificity, and accuracy of 0.827, 0.913, and 0.827, respectively. The prevalence analysis of delirium showed that the NLP-CAM algorithm identified 12 651 (9.4%) delirium patients, the NLP-mCAM algorithm identified 20 611 (15.3%) definite delirium cases, and 10 762 (8.0%) possible cases. Conclusions NLP algorithms based on the standardized evidence-based CAM framework demonstrated high performance in delineating delirium status in an expeditious and cost-effective manner.

OBJECTIVE To assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACE) after adjusting for established cardiovascular disease (CVD) risk factors. PATIENTS AND METHODS We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients aged >30 with a clinical encounter from 1998-2000 with no prior MACE, atrial fibrillation, or heart failure, were followed through March 1, 2016. BD diagnosis was validated by chart review. Cox proportional hazards regression models were adjusted for established CVD risk factors, alcohol use disorder (AUD), other substance use disorders (SUD), and major depressive disorder (MDD). RESULTS The cohort included 288 individuals with BD (0.81%) and 35,326 individuals without BD as the reference group (Ref). Median (IQR) follow-up was 16.5 (14.6-17.5) years. 5636 MACE events occurred (BD: 59, Ref: 5577). Survival analysis showed an association between BD and MACE (median event-free-survival rates BD: 0.80, Ref: 0.86; log-rank P = .018). Multivariate regression adjusting for age and sex also yielded an association between BD and MACE (HR: 1.93; 95% CI: 1.43-2.52; P < .001). The association remained significant after further adjusting for smoking, diabetes mellitus, hypertension, HDL cholesterol, and body mass index (HR: 1.66; 95% CI 1.17-2.28; P = .006), and for AUD, SUD, and MDD (HR: 1.56; 95% CI 1.09-2.14; P = .010). CONCLUSION In this study, BD was associated with an increased risk of MACE which persisted after adjusting for established CVD risk factors, SUDs, and MDD. These results suggest that BD is an independent risk factor for major clinical cardiac disease outcomes.

The associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial.To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance.This case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021.Medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP).Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years.Among 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259 women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, -0.17; 95% CI, -0.32 to -0.03; P = .02), attention and executive domain z score (β, -0.21; 95% CI, -0.36 to -0.05; P = .009), and Short Test of Mental Status score (β, -0.51; 95% CI, -0.95 to -0.08; P = .02) compared with no bilateral oophorectomy.This study found that women who underwent bilateral oophorectomy before menopause had increased odds of MCI and poorer performance on cognitive tests approximately 30 years later compared with women who did not undergo bilateral oophorectomy.

To study the trajectories of metabolic parameters after bilateral oophorectomy.This population-based cohort study included a random sample of all premenopausal women who underwent bilateral oophorectomy at or before age 45 years from 1988 to 2007 in Olmsted County, Minnesota, and their age-matched (±1 year) referent women who did not undergo bilateral oophorectomy.The medical records of all women were reviewed to collect the metabolic parameters over a 10-year period. We compared three groups of women: 1) referent women (n = 270), 2) women who underwent bilateral oophorectomy and received estrogen therapy (n = 163), and 3) women who underwent bilateral oophorectomy and did not receive estrogen therapy (n = 107).Over 10 years of follow-up, the three groups had significantly different mean values of diastolic blood pressure, weight, body mass index (BMI), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). However, women with and without bilateral oophorectomy were already different at baseline for hyperlipidemia, systolic blood pressure, weight, and BMI. Nevertheless, the trajectories of change over 10 years were significant for weight (group by time interaction p = 0.03), BMI (p = 0.03), and HDL-C (p = 0.004). The changes occurred primarily in the initial 4-5 years. Women who received estrogen therapy after bilateral oophorectomy were comparable to the referent women with respect to the weight and BMI trends, and they experienced an increase in HDL-C over time.Women who underwent bilateral oophorectomy before menopause experienced unfavorable changes in some metabolic parameters possibly increasing their cardiovascular risk.

OBJECTIVE: Despite the fact that negative mood and executive dysfunction are common following risk-reducing salpingo-oophorectomy (RRSO) – occurring in up to a third of women – little is known about risk factors predicting these negative outcomes. Adverse childhood experiences (ACE) predict poorer health in adulthood and may be a risk factor for negative outcomes following RRSO. Given the complex relationship between early life stress, affective disorders, and cognitive dysfunction, we hypothesized that ACE would be associated with poorer executive function and that mood symptoms would partially mediate this relationship. METHODS: Women who had undergone RRSO were included in the study (N = 552; age 30–73 years). We measured executive function (continuous performance task, letter n-back task, Brown Attention Deficit Disorder Scale Score), exposure to early life stress (ACE Questionnaire), and mood symptoms (Hospital Anxiety and Depression Scale). Generalized estimating equations were used to evaluate the association between ACE and executive dysfunction and the role of mood symptoms as a mediator in this relationship. RESULTS: ACE was associated with greater severity of subjective executive dysfunction (adjusted mean difference (aMD)= 7.1, p=0.0005) and worse performance on both cognitive tasks (CPT: aMD=−0.1, p=0.03; n-back: aMD=−0.17, p=0.007). Mood symptoms partially mediated ACE associations with sustained attention (21.3% mediated; 95% CI: 9.3% - 100%) and subjective report of executive dysfunction (62.8% mediated; 95% CI: 42.3% - 100%). CONCLUSIONS: The relationship between childhood adversity and executive dysfunction is partially mediated by mood symptoms. These data indicate that assessing history of childhood adversity and current anxiety and depression symptoms may play a role in treating women who report cognitive complaints after RRSO.

Background Persons with low socioeconomic status may be disproportionately at risk for multimorbidity. Methods Adults aged ≥20 years on 4/1/2015 from 7 counties in Minnesota were identified using the Rochester Epidemiology Project (population-based sample). A composite measure of neighborhood socioeconomic disadvantage, the area deprivation index (ADI), was estimated at the census block group level (n = 251). The prevalence of 21 chronic conditions was obtained to calculate the proportion of persons with multimorbidity (≥2 chronic conditions) and severe multimorbidity (≥5 chronic conditions). Hierarchical logistic regression was used to estimate the association of ADI with multimorbidity and severe multimorbidity using odds ratios (OR). Results Among 198,941 persons (46.7% male, 30.6% aged ≥60 years), the age- and sex-standardized (to the United States 2010 census) median prevalence (Q1, Q3) was 23.4% (21.3%, 25.9%) for multimorbidity and 4.8% (4.0%, 5.7%) for severe multimorbidity. Compared with persons in the lowest quintile of ADI, persons in the highest quintile had a 50% increased risk of multimorbidity (OR 1.50, 95% CI 1.39–1.62) and a 67% increased risk of severe multimorbidity (OR 1.67, 95% CI 1.51–1.86) after adjusting for age, sex, race, and ethnicity. Associations were stronger after further adjustment for individual level of education; persons in the highest quintile had a 78% increased risk of multimorbidity (OR 1.78, 95% CI 1.62–1.96) and a 92% increased risk of severe multimorbidity (OR 1.92, 95% CI 1.72–2.13). There was evidence of interactions between ADI and age, between ADI and sex, and between ADI and education. After age 70 years, no difference in the risk of multimorbidity was observed across quintiles of ADI. The pattern of increasing multimorbidity with increasing ADI was more pronounced in women. Finally, there was less variability across quintiles of ADI for the most highly educated group. Conclusions Higher ADI was associated with increased risk of multimorbidity, and the associations were strengthened after adjustment for individual level of education, suggesting that neighborhood context plays a role in health above and beyond individual measures of socioeconomic status. Furthermore, associations were more pronounced in younger persons and women, highlighting the importance of interventions to prevent chronic conditions in younger women, in particular.

Objective The aim of this research was to study the long-term risk of de novo mental health conditions in women who underwent hysterectomy with bilateral ovarian conservation compared with age-matched referent women. Methods Using the Rochester Epidemiology Project records-linkage system, we identified a historical cohort of 2,094 women who underwent hysterectomy with ovarian conservation for benign indications at age ≥18 years and with an index date between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone hysterectomy or any oophorectomy before the index date. These two cohorts were followed historically to identify de novo mental health conditions. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases (ARIs) and reductions (ARRs) at 30 years of follow-up. Results Over a median follow-up of 21.9 years, women who underwent hysterectomy at any age experienced increased risks of de novo depression (adjusted HR 1.26; 95% CI, 1.12-1.41; ARI 6.6%) and anxiety (adjusted HR 1.22; 95% CI, 1.08-1.38; ARI 4.7%). The association for depression increased significantly with younger age at hysterectomy, but did not vary significantly by indication. Interactions were not significant for anxiety. Conclusions Hysterectomy, even with ovarian conservation, is associated with an increased long-term risk of de novo depression and anxiety, especially when performed in women who are younger. : Video Summary:http://links.lww.com/MENO/A465.

Objective To identify risk factors associated with severe COVID-19 infection in a defined Midwestern US population overall and within different age groups. Patients and Methods We used the Rochester Epidemiology Project research infrastructure to identify persons residing in a defined 27-county Midwestern region who had positive results on polymerase chain reaction tests for COVID-19 between March 1, 2020, and September 30, 2020 (N=9928). Age, sex, race, ethnicity, body mass index, smoking status, and 44 chronic disease categories were considered as possible risk factors for severe infection. Severe infection was defined as hospitalization or death caused by COVID-19. Associations between risk factors and severe infection were estimated using Cox proportional hazard models overall and within 3 age groups (0 to 44, 45 to 64, and 65+ years). Results Overall, 474 (4.8%) persons developed severe COVID-19 infection. Older age, male sex, non-White race, Hispanic ethnicity, obesity, and a higher number of chronic conditions were associated with increased risk of severe infection. After adjustment, 36 chronic disease categories were significantly associated with severe infection. The risk of severe infection varied significantly across age groups. In particular, persons 0 to 44 years of age with cancer, chronic neurologic disorders, hematologic disorders, ischemic heart disease, and other endocrine disorders had a greater than 3-fold increased risk of severe infection compared with persons of the same age without those conditions. Associations were attenuated in older age groups. Conclusion Older persons are more likely to experience severe infections; however, severe cases occur in younger persons as well. Our data provide insight regarding younger persons at especially high risk of severe COVID-19 infection.

Context While adrenal adenomas have been linked with cardiovascular morbidity in convenience samples of patients from specialized referral centers, large-scale population-based data are lacking. Objective To determine the prevalence and incidence of cardiometabolic disease and assess mortality in a population-based cohort of patients with adrenal adenomas. Design Population-based cohort study. Setting Olmsted County, Minnesota, USA. Patients Patients diagnosed with adrenal adenomas without overt hormone excess and age- and sex-matched referent subjects without adrenal adenomas. Main outcome measure Prevalence, incidence of cardiometabolic outcomes, mortality. Results (Adrenal adenomas were diagnosed in 1004 patients (58% women, median age 63 years) from 1/01/1995 to 12/31/2017. At baseline, patients with adrenal adenomas were more likely to have hypertension [adjusted odds ratio (aOR) 1.96, 95% CI 1.58-2.44], dysglycemia (aOR 1.63, 95% CI 1.33-2.00), peripheral vascular disease (aOR 1.59, 95% CI 1.32-2.06), heart failure (aOR 1.64, 95% CI 1.15-2.33), and myocardial infarction (aOR 1.50, 95% CI 1.02-2.22) compared to referent subjects. During median follow-up of 6.8 years, patients with adrenal adenomas were more likely than referent subjects to develop de novo chronic kidney disease [adjusted hazard ratio (aHR) 1.46, 95% CI 1.14-1.86], cardiac arrhythmia (aHR 1.31, 95% CI 1.08-1.58), peripheral vascular disease (aHR 1.28, 95% CI 1.05-1.55), cardiovascular events (aHR 1.33, 95% CI 1.01-1.73), and venous thromboembolic events (aHR 2.15, 95% CI 1.48-3.13). Adjusted mortality was similar between the 2 groups. Conclusion Adrenal adenomas are associated with an increased prevalence and incidence of adverse cardiometabolic outcomes in a population-based cohort.

PurposeThe depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data.ParticipantsAll individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013.Findings to dateFor the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline.Future plansUsing advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR.

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.

Objective To assess the validity of the US Department of Health and Human Services (DHHS) definition of multimorbidity using International Classification of Diseases, ninth edition (ICD-9) codes from administrative data. Design Cross-sectional comparison of two ICD-9 billing code algorithms to data abstracted from medical records. Setting Olmsted County, Minnesota, USA. Participants An age-stratified and sex-stratified random sample of 1509 persons ages 40–84 years old residing in Olmsted County on 31 December 2010. Study measures Seventeen chronic conditions identified by the US DHHS as important in studies of multimorbidity were identified through medical record review of each participant between 2006 and 2010. ICD-9 administrative billing codes corresponding to the 17 conditions were extracted using the Rochester Epidemiology Project records-linkage system. Persons were classified as having each condition using two algorithms: at least one code or at least two codes separated by more than 30 days. We compared the ICD-9 code algorithms with the diagnoses obtained through medical record review to identify persons with multimorbidity (defined as ≥2, ≥3 or ≥4 chronic conditions). Results Use of a single code to define each of the 17 chronic conditions resulted in sensitivity and positive predictive values (PPV) ≥70%, and in specificity and negative predictive values (NPV) ≥70% for identifying multimorbidity in the overall study population. PPV and sensitivity were highest in persons 65–84 years of age, whereas NPV and specificity were highest in persons 40–64 years. The results varied by condition, and by age and sex. The use of at least two codes reduced sensitivity, but increased specificity. Conclusions The use of a single code to identify each of the 17 chronic conditions may be a simple and valid method to identify persons who meet the DHHS definition of multimorbidity in populations with similar demographic, socioeconomic, and health care characteristics.

Background Electronic health records (EHRs) are a rich source of longitudinal patient data. However, missing information due to clinical care that predated the implementation of EHR system(s) or care that occurred at different medical institutions impedes complete ascertainment of a patient’s medical history. Objective This study aimed to investigate information discrepancies and to quantify information gaps by comparing the gynecological surgical history extracted from an EHR of a single institution by using natural language processing (NLP) techniques with the manually curated surgical history information through chart review of records from multiple independent regional health care institutions. Methods To facilitate high-throughput evaluation, we developed a rule-based NLP algorithm to detect gynecological surgery history from the unstructured narrative of the Mayo Clinic EHR. These results were compared to a gold standard cohort of 3870 women with gynecological surgery status adjudicated using the Rochester Epidemiology Project medical records–linkage system. We quantified and characterized the information gaps observed that led to misclassification of the surgical status. Results The NLP algorithm achieved precision of 0.85, recall of 0.82, and F1-score of 0.83 in the test set (n=265) relative to outcomes abstracted from the Mayo EHR. This performance attenuated when directly compared to the gold standard (precision 0.79, recall 0.76, and F1-score 0.76), with the majority of misclassifications being false negatives in nature. We then applied the algorithm to the remaining patients (n=3340) and identified 2 types of information gaps through error analysis. First, 6% (199/3340) of women in this study had no recorded surgery information or partial information in the EHR. Second, 4.3% (144/3340) of women had inconsistent or inaccurate information within the clinical narrative owing to misinterpreted information, erroneous “copy and paste,” or incorrect information provided by patients. Additionally, the NLP algorithm misclassified the surgery status of 3.6% (121/3340) of women. Conclusions Although NLP techniques were able to adequately recreate the gynecologic surgical status from the clinical narrative, missing or inaccurately reported and recorded information resulted in much of the misclassification observed. Therefore, alternative approaches to collect or curate surgical history are needed.

ObjectivesTo describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality.DesignPopulation-based descriptive study and cohort study.SettingOlmsted County, Minnesota (USA).ParticipantsWe 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).MethodsFor each person, we obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person’s count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP.ResultsWe identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3–10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women.ConclusionsThe assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.

In this invited review, we discuss some unresolved and controversial issues concerning premature (

This cohort study assesses whether bilateral oophorectomy for a benign indication prior to natural menopause is associated with risk of restless legs syndrome., Key Points Question Is bilateral oophorectomy for a benign indication prior to natural menopause associated with risk of restless legs syndrome? Findings In this cohort study of 3306 women, those who underwent bilateral oophorectomy prior to natural menopause had a higher risk of restless legs syndrome than those who did not undergo such surgery. The increased risk was independent of multiple chronic conditions present at baseline, was greater among women without a benign ovarian condition, and did not differ by estrogen therapy. Meaning This study found that undergoing bilateral oophorectomy for a benign indication prior to natural menopause was associated with an increased risk of restless legs syndrome., Importance Restless legs syndrome is a common neurologic disorder that is more prevalent in women than in men, and it has been suggested that female hormones may be involved in the disorder’s pathophysiology. Objective To determine whether women who underwent premenopausal bilateral oophorectomy were at increased risk of restless legs syndrome. Design, Setting, and Participants This cohort study was performed using data from the Mayo Clinic Cohort Study of Oophorectomy and Aging–2 for a population in Olmsted County, Minnesota. There were 1653 women who underwent premenopausal bilateral oophorectomy before the age of 50 years for a benign indication between 1988 and 2007 and 1653 age-matched women (of same age plus or minus 1 year) in a reference group. Follow-up was conducted until the end of the study period (ie, December 31, 2014). Data were analyzed from January to July 2020. Exposures Undergoing bilateral oophorectomy, as shown in medical record documentation. Main Outcomes and Measures Diagnosis of restless legs syndrome, as defined using Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria, was recorded. Results Among 3306 women, the median (interquartile range) age at baseline was 44.0 (40.0-47.0) years. Women who underwent bilateral oophorectomy, compared with women who did not undergo this procedure, had a greater number of chronic conditions at the index date (eg, 300 women [18.1%] vs 171 women [10.3%] with ≥3 chronic conditions; overall P

Objective Several small studies reported increased prevalence and incidence of asymptomatic vertebral fractures in patients with non-functioning adrenal adenomas and adenomas with mild autonomous cortisol secretion. However, the risk of symptomatic fractures at vertebrae, and at other sites remains unknown. Our objective was to determine the prevalence and incidence of symptomatic site-specific fractures in patients with adrenal adenomas. Design Population-based cohort study, Olmsted County, Minnesota, USA, 1995–2017. Methods Participants were the patients with adrenal adenoma and age/sex-matched referent subjects. Patients with overt hormone excess were excluded. Main outcomes measures were prevalence and incidence of bone fractures. Results Of 1004 patients with adrenal adenomas, 582 (58%) were women, and median age at diagnosis was 63 years (20–96). At the time of diagnosis, patients had a higher prevalence of previous fractures than referent subjects (any fracture: 47.9% vs 41.3%, P = 0.003, vertebral fracture: 6.4% vs 3.6%, P = 0.004, combined osteoporotic sites: 16.6% vs 13.3%, P = 0.04). Median duration of follow-up was 6.8 years (range: 0–21.9 years). After adjusting for age, sex, BMI, tobacco use, prior history of fracture, and common causes of secondary osteoporosis, patients with adenoma had hazard ratio of 1.27 (95% CI: 1.07–1.52) for developing a new fracture during follow up when compared to referent subjects. Conclusions Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis and increased risk to develop new fractures when compared to referent subjects.

Background Persons with low socioeconomic status may be disproportionately at risk for multimorbidity. Methods Adults aged ≥20 years on 4/1/2015 from 7 counties in Minnesota were identified using the Rochester Epidemiology Project (population-based sample). A composite measure of neighborhood socioeconomic disadvantage, the area deprivation index (ADI), was estimated at the census block group level (n = 251). The prevalence of 21 chronic conditions was obtained to calculate the proportion of persons with multimorbidity (≥2 chronic conditions) and severe multimorbidity (≥5 chronic conditions). Hierarchical logistic regression was used to estimate the association of ADI with multimorbidity and severe multimorbidity using odds ratios (OR). Results Among 198,941 persons (46.7% male, 30.6% aged ≥60 years), the age- and sex-standardized (to the United States 2010 census) median prevalence (Q1, Q3) was 23.4% (21.3%, 25.9%) for multimorbidity and 4.8% (4.0%, 5.7%) for severe multimorbidity. Compared with persons in the lowest quintile of ADI, persons in the highest quintile had a 50% increased risk of multimorbidity (OR 1.50, 95% CI 1.39–1.62) and a 67% increased risk of severe multimorbidity (OR 1.67, 95% CI 1.51–1.86) after adjusting for age, sex, race, and ethnicity. Associations were stronger after further adjustment for individual level of education; persons in the highest quintile had a 78% increased risk of multimorbidity (OR 1.78, 95% CI 1.62–1.96) and a 92% increased risk of severe multimorbidity (OR 1.92, 95% CI 1.72–2.13). There was evidence of interactions between ADI and age, between ADI and sex, and between ADI and education. After age 70 years, no difference in the risk of multimorbidity was observed across quintiles of ADI. The pattern of increasing multimorbidity with increasing ADI was more pronounced in women. Finally, there was less variability across quintiles of ADI for the most highly educated group. Conclusions Higher ADI was associated with increased risk of multimorbidity, and the associations were strengthened after adjustment for individual level of education, suggesting that neighborhood context plays a role in health above and beyond individual measures of socioeconomic status. Furthermore, associations were more pronounced in younger persons and women, highlighting the importance of interventions to prevent chronic conditions in younger women, in particular.

OBJECTIVE. To investigate the extent to which antibiotic exposure in the first two years of life is associated with the risk of immunological, metabolic, and neurobehavioral health conditions with childhood onset. PATIENTS AND METHODS. In this population-based cohort study we identified all children born in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2011 through the Rochester Epidemiology Project (REP) medical records-linkage system. Demographic characteristics, antibiotic prescriptions, and diagnostic codes through June 30, 2017 were retrieved using the REP infrastructure. Time-to-event analysis was conducted to assess the impact of antibiotic exposure on the risk of several adverse health conditions. RESULTS. This study included 14,572 children (7,026 girls and 7,546 boys), of whom 70% received at least one antibiotic prescription during the first two years of life. Early antibiotic exposure was associated with an increased risk of childhood onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, and attention deficit hyperactivity disorder (hazard ratios ranging from 1.20 to 2.89, all P

Adrenal tumours are commonly encountered in clinical practice, but epidemiological data mainly originate from referral centres. We aimed to determine incidence, prevalence, and rates of malignancy and hormone excess in patients with adrenal tumours in a standardised geographically well defined population.In this retrospective population-based cohort study we assessed the standardised incidence rate of adrenal tumours in all patients with tumours who lived in Olmsted County, MN, USA, from Jan 1, 1995, to Dec 31, 2017. The Rochester Epidemiology Project infrastructure, which links medical records across all health-care providers for the entire population of Olmsted County since 1966, was used to allow researchers to identify individuals with specific diagnoses, surgical interventions, and other procedures, and to locate their medical records, which were then used in the analysis. Incidence rates and prevalence were standardised for age and sex according to the 2010 US Population.An adrenal tumour was diagnosed in 1287 patients (median age 62 years; 713 (55·4%) were women; and 13 (1·0%) were children). Standardised incidence rates increased from 4·4 (95% CI 0·3-8·6) per 100 000 person-years in 1995 to 47·8 (36·9-58·7) in 2017, mainly because of the incidental discovery of adenomas less than 40 mm in diameter in patients older than 40 years. Prevalence of adrenal tumours in 2017 was 532 per 100 000 inhabitants, ranging from 13 per 100 000 in children (aged18 years) to 1900 per 100 000 in patients older than 65 years. 111 (8·6%) of 1287 patients were diagnosed with malignancy (96 [7·5%] of whom has metastases), 14 (1·1%) with phaeochromocytoma, and 53 (4·1%) with overt steroid hormone excess. Malignancy was more common in children (62%) versus those older than 18 years (8%; p0·0001), tumours discovered during cancer-staging or follow-up (43% vs 3% for incidentalomas; p0·0001), tumours more than 40 mm in diameter (34% vs 6% for tumours20 mm; p0·0001), tumours with unenhanced CT attenuation of 30 Hounsfield units or more (20% vs 1% for20 Hounsfield units; p·0001), and bilateral masses (16% vs 7% for unilateral, p=0·0004).Adrenal tumour standardised incidence rates increased 10 times from 1995 to 2017. Population-based data revealed lower rates of malignancy, phaeochromocytoma, and overt steroid hormone excess than previously reported.National Institutes of Health.

Background: Adrenal tumors are reported in 5% of adults, with malignancy rates in 1–12%, and rates of overt hormonal excess in 1–15 %. However, most estimates originate from convenience samples. Our objective was to determine the incidence, prevalence and clinical presentation of adrenal tumors in a population-based setting. Methods: We used a centralized epidemiologic database to identify patients diagnosed with adrenal tumors in a local community 1995 to 2017. The database is a unique medical records linkage system that allows access to hospital and community medical records for local residents (population 137,000). We calculated incidence rates (IR) as the number of new patients diagnosed while living in the study area, and prevalence as the number of patients living in the study area on Dec 31 2017. IR and prevalence were sex- and age-adjusted to the 2010 US Census population. Results: Of 1,287 patients diagnosed with adrenal tumor, the median age of diagnosis was 62 years (IQR 52–72), 713 (55%) were women, and 13 (1%) were younger than 18 years at diagnosis. IR was highest in patients >65 YO, followed by patients 40–64 YO, 18–39 YO and Malignant adrenal mass was diagnosed in 8.7% patients (4 patients with adrenal cortical carcinoma (0.3%) and 108 (8.4%) patients with other malignant mass). Pheochromocytoma was diagnosed in 11 (1.1%) patients and benign adrenal mass was diagnosed in 1,175 (90.2%) patients (1,076 (83.6%) with adrenal adenoma and 85 (6.6%) with other benign mass). Median tumor size was 15 mm (range 5–255), and 184 (14%) of patients had bilateral tumors. Only 255 (20%) patients had dexamethasone suppression test, 93 (36%) with cortisol>1.8 mcg/dl. Of 1,076 adrenal adenomas, 53 (4.9%) had overt hormone excess, 140 (13%) had nonfunctioning adrenal adenomas, and 88 (8.2%) had mild autonomous cortisol secretion. Hormonal work up for was incomplete in 795 (73.9%) adenomas. Patients discovered incidentally (1,050, 81.6%) had a lower rate of malignancy and hormone excess (5.3% vs 52% of patients with non-incidental discovery, p 18YO, p Conclusion: IR of adrenal tumors increased 10-fold since 1995, and was highest in patients >65 YO. 8.7% of tumors were malignant, with a majority represented by malignant adrenal tumors other than adrenal cortical carcinoma. The risk of malignancy was highest in non-incidental discovery, children, and tumors > 4 cm. Overt hormone excess was diagnosed in 4.5% of patients. The majority of patients with adrenal adenomas had a suboptimal work up for hormone excess.