Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation.

In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared with matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium- and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < .001), increases in both parathyroid hormone (when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = .03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < .001), and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency toward thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Older Tissue Age Derived From Abdominal Computed Tomography Biomarkers of Muscle, Fat, and Bone Is Associated With Chronic Conditions and Higher Mortality.

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.

Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.

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.

Fracture Risk Among Living Kidney Donors 25 Years After Donation.

Importance: Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective: To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants: This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure: Living kidney donation. Main Outcomes and Measures: The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results: At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance: This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

Integrating Environmental Data with Medical Data in a Records-Linkage System to Explore Groundwater Nitrogen Levels and Child Health Outcomes.

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.

Synergistic interactions of obesity with sex, education, and smoking and accumulation of multi-morbidity (MM) across the lifespan.

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.

Convergence of four measures of multi-morbidity.

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.

Association of Depression and Anxiety With the Accumulation of Chronic Conditions.

Importance: Longitudinal associations between comorbid depression and anxiety with the accumulation of chronic illnesses are unclear, and questions remain about the contributions associated with each condition in the increasing prevalence of multimorbidity. Objective: To compare the risk and rate of accumulating chronic conditions in people with depression, anxiety, and comorbid depression and anxiety vs individuals with neither depression nor anxiety. Design, Setting, and Participants: This cohort study used the Rochester Epidemiology Project medical records-linkage system to identify residents of Olmsted County, Minnesota, from January 1, 2005, to December 31, 2014, with follow-up ending December 31, 2017. The sample was divided into cohorts anchored at birthday ages of 20, 40, and 60 years. Individuals were classified at anchoring birthday age as having depression alone, anxiety alone, comorbid depression and anxiety, or neither depression nor anxiety (reference group), using electronically extracted diagnosis codes from the International Classification of Diseases, Ninth Revision (ICD-9) in the 5 years before each anchoring birthday. Data were analyzed from August 2020 through November 2021. Exposures: Depression alone, anxiety alone, comorbid depression and anxiety, or neither depression nor anxiety (reference group). Main Outcomes and Measures: The main outcome was sex-specific risk, calculated as hazard ratios (HRs) and rates of accumulation, calculated as mean annual incidence rates per 100 person-years, of 15 common chronic conditions within each birthday age cohort through the end of study. Results: Among the 40 360 individuals included across all 3 age cohorts, 21 516 (53.3%) were women. After balancing cohorts on race, Hispanic ethnicity, education level, body mass index, smoking status, and calendar year at index birthday, the risk of accumulating chronic conditions was significantly increased among women with depression alone (cohort aged 20 years: HR, 1.20 [95% CI, 1.02-1.42]; cohort aged 40 years: HR, 1.20 [95% CI, 1.10-1.31]; cohort aged 60 years: HR, 1.09 [95% CI, 1.02-1.16]) and women with comorbid depression and anxiety (cohort aged 20 years: HR, 1.60 [95% CI, 1.28-1.99]; cohort aged 40 years: HR, 1.41 [95% CI, 1.21-1.65]; cohort aged 60 years: HR, 1.29 [95% CI, 1.15-1.44]) compared with referent women in the same birthday cohorts and in men with comorbid depression and anxiety compared with referent men in the cohort aged 20 years (HR, 1.77 [95% CI, 1.08-2.91]). For women, the rates of accumulation of conditions were significantly higher across birthday cohorts in the comorbid depression and anxiety group compared with the depression alone group (eg, cohort aged 20 years: difference, 1.2 [95% CI, 0.2-2.1] per 100 person-years) and reference group (eg, cohort aged 20 years: difference, 1.7 [95% CI, 0.9-2.6] per 100 person-years). For men, compared with the reference group, the rates of accumulation of conditions were significantly higher in men with comorbid depression and anxiety in the cohort aged 20 years (difference, 1.4 [95% CI, 0.1-2.6] per 100 person-years) and in men with depression in the cohort aged 40 years (difference, 2.0 [95% CI, 0.8-3.2] per 100 person-years). Conclusions and Relevance: In this cohort study, the risk of accumulating chronic conditions was increased with depression and comorbid depression and anxiety in women across the age span and in younger men with comorbid depression and anxiety. Compared with women without depression or anxiety, there was a more rapid rate of accumulation of chronic conditions in women with depression and anxiety individually and an even higher rate when depression and anxiety cooccurred.

Implementing the US Department of Health and Human Services definition of multimorbidity: a comparison between billing codes and medical record review in a population-based sample of persons 40-84 years old.

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.

Multimorbidity, ageing and mortality: normative data and cohort study in an American population.

OBJECTIVES: To describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality. DESIGN: Population-based descriptive study and cohort 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 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. RESULTS: We 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. CONCLUSIONS: The 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.

Pregnancy, Estrogen Exposure, and the Development of Otosclerosis: A Case-Control Study of 1196 Women.

OBJECTIVE: This study sought to determine whether a history of pregnancy or bilateral oophorectomy is associated with subsequent otosclerosis development or disease severity. STUDY DESIGN: Population-based case-control study. SETTING: Olmsted County, Minnesota. METHODS: Women diagnosed with otosclerosis were matched to 3 women without otosclerosis based on age and historical depth of medical records. Associations of prior delivery and bilateral oophorectomy with subsequent development of otosclerosis and with pure-tone average (PTA) at the time of otosclerosis diagnosis were evaluated. RESULTS: We studied 1196 women: 299 cases of otosclerosis and 897 matched controls. The odds ratio for the association of ≥1 delivery with otosclerosis was 1.16 (95% confidence interval [CI] 0.85-1.60; P = .35). Odds ratios for the associations of 1, 2, 3, or ≥4 deliveries with otosclerosis were 1.22 (0.83-1.80), 1.09 (0.71-1.68), 1.28 (0.77-2.12), and 1.00 (0.54-1.84), respectively. The odds ratio for the association of prior bilateral oophorectomy with otosclerosis was 1.12 (0.58-2.18; P = .73). In cases with otosclerosis, PTA at diagnosis was not significantly higher for women with ≥1 delivery as compared with those without (median 45 dB hearing loss [HL] [interquartile range {IQR} 36-55] vs 43 [IQR 34-53]; P = 0.18) but was significantly higher for women with bilateral oophorectomy compared with those without (median 54 dB HL [IQR 44-61] vs 44 [IQR 34-53]; P = .03). CONCLUSION: These data do not support a relationship between endogenous estrogen exposure and development of otosclerosis. Women with otosclerosis who had a history of pregnancy did not have significantly worse hearing at the time of diagnosis, suggesting that pregnancy is not associated with disease severity.

The Rise and Fall of Otosclerosis: A Population-based Study of Disease Incidence Spanning 70 Years.

OBJECTIVE: Although it is commonly held that otosclerosis has become increasingly uncommon over recent decades, no population-based data exist to characterize this trend. Moreover, because most large epidemiologic databases within the United States primarily include cancer data, even the modern incidence of otosclerosis is unknown. The chief objective of the current work was to characterize the trend in the incidence of otosclerosis over 70 years using the unique resources of the Rochester Epidemiology Project. STUDY DESIGN: Population-based study. PATIENTS: Residents of Olmsted County, Minnesota diagnosed with otosclerosis. MAIN OUTCOME MEASURE: Disease incidence from 1950 to 2017. RESULTS: From 1950 to 2017, 614 incident cases of otosclerosis were identified. The incidence rose from 8.9 per 100,000 person-years in the 1950s to a peak of 18.5 from 1970 to 1974. From this peak, the incidence significantly declined to 6.2 per 100,000 person-years by the early-1990s and reached a nadir of 3.2 from 2015 to 2017 (p<0.001). From 1970 to 2017, age at diagnosis (p = 0.23) and the proportion of bilateral cases (p = 0.16) did not significantly change; pure-tone average at diagnosis did not clinically appreciably change over the study period (median difference <5 dB across decades, p = 0.034). CONCLUSIONS: The incidence of otosclerosis drastically declined since the early-1970s. Historically considered one of the most common causes of acquired hearing loss, the low modern incidence of otosclerosis renders it legally a "rare disease" within the United States. These trends require consideration when determining trainee case requirements and developing practice guidelines.

Rising Incidence of Sporadic Vestibular Schwannoma: True Biological Shift Versus Simply Greater Detection.

OBJECTIVE: The incidence of sporadic vestibular schwannoma (VS) has increased significantly over recent decades. The rising incidence of VS has been largely attributed to the increasing use of magnetic resonance imaging (MRI), especially with regard to incidentally diagnosed tumors. However, no study to date has directly investigated this supposed etiology beyond the observation that VS incidence rates have risen in the post-MRI era. Therefore, the primary objective of the current study was to characterize the incidence of head MRIs over the previous two decades in Olmsted County, Minnesota and compare this trend to the incidence of asymptomatic, incidentally diagnosed VS over the same time period. STUDY DESIGN: Population-based incidence study. SETTING/PATIENTS: Using the unique resources of the Rochester Epidemiology Project, procedure codes for head MRIs and diagnostic codes for VS among residents of Olmsted County, Minnesota between Jan 1, 1995 and Dec 31, 2016 were retrieved. Incidence rates of head MRI and incidentally diagnosed VS were calculated on a per-year basis. RESULTS: A total of 43,561 head MRIs among 30,002 distinct persons were identified from 1995 to 2016. The incidence of head MRI significantly increased between 1995 and 2003 (p < 0.001), but remained stable between 2004 and 2016 (p = 0.14). Over the same time interval, 25 cases of incidentally diagnosed VS were identified. The incidence of asymptomatic VS increased over time from 0.72 per 100,000 person-years between 1995 and 1999 to 1.29 between 2012 and 2016 (p = 0.058). No plateauing of incidence rates was observed in incidental tumors over the study period. The size of incidentally diagnosed tumors did not change over the study period (p = 0.93), suggesting that the increasing incidence of asymptomatic tumors is not explained by improved diagnostic capability of more recent MRI studies. CONCLUSIONS: Despite the plateauing of head MRI incidence rates after 2004, the incidence of asymptotic, incidentally diagnosed VS continued to increase. Our findings suggest that there may be additional contributory etiologies for the rising incidence of VS beyond greater detection alone.

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

OBJECTIVE: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications. METHODS: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression. RESULTS: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001). CONCLUSIONS: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.

Prevalence of Sporadic Vestibular Schwannoma: Reconciling Temporal Bone, Radiologic, and Population-based Studies.

OBJECTIVE: Reported epidemiologic data surrounding vestibular schwannoma (VS) are controversial. Temporal bone prevalence studies have suggested that VS affects up to 2.4% of the population, whereas magnetic resonance imaging (MRI) studies have reported VS to affect 0.017%. Moreover, existing population-based data seem to underestimate the commonness of VS. In an attempt to reconcile temporal bone, radiologic, and population-based reports regarding VS, the current study was conceived to determine the modern prevalence of VS using a unique epidemiological database. PATIENTS: All persons living in Olmsted County, Minnesota on January 1, 2017 with a confirmed diagnosis of sporadic VS identified using the Rochester Epidemiology Project (REP) medical records-linkage system. MAIN OUTCOME MEASURES: Prevalence of all VS and asymptomatic, incidentally diagnosed VS. RESULTS: Sixty-seven persons from a population of nearly 160,000 were living with VS on January 1, 2017, resulting in a point prevalence of 42.0 per 100,000 persons. The prevalence increased with older age, reaching 212.4 per 100,000 in those ≥ 70 years. Including only persons who have undergone head MRI, the prevalence of asymptomatic, incidentally diagnosed VS was 69.9 per 100,000 among adults age 20 years and older. CONCLUSIONS: Using the unique infrastructure of the REP, the current study suggests that the clinical prevalence of sporadic VS approximates 1 in 2,000 adults and 1 in every 500 persons aged 70 years and older, with the prevalence of incidentally diagnosed tumors closely paralleling past MRI studies. These data characterize a shift in the modern patient demographic of sporadic VS, as now many people bearing a diagnosis of VS would have previously died without knowledge of their disease. Moreover, they typify an unfolding transition from an era of microsurgery and radiosurgery to the beginnings of an era that will be largely comprised of "chronic disease management."

Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population.

The purpose of this study was to estimate the extent of potential antidepressant overprescribing in a geographically defined U.S. population, and to determine the indications and factors that account for it. We conducted a cohort study of new antidepressant prescriptions for elderly residents of Olmsted County, Minnesota, 2005-2012, using the Rochester Epidemiology Project medical records-linkage system. Indications for antidepressants were abstracted from health records for all cohort members. Potential antidepressant overprescribing was defined based on regulatory approval, the level of evidence identified from a standardized drug information database, and multidisciplinary expert review. Predictors of potential antidepressant overprescribing were investigated using logistic regression models, stratified by general antidepressant indication (general medical indication, specific psychiatric diagnosis, and non-specific psychiatric symptoms). Potential antidepressant overprescribing occurred in 24% of 3199 incident antidepressant prescriptions during the study period, and involved primarily newer antidepressants that were prescribed for non-specific psychiatric symptoms and subthreshold diagnoses. Potential antidepressant overprescribing was associated with nursing home residence, having a higher number of comorbid medical conditions and outpatient prescribers, taking more concomitant medications, having greater use of urgent or acute care services in the year preceding the index antidepressant prescription, and being prescribed antidepressants via telephone, e-mail, or patient portal. In conclusion, potential antidepressant overprescribing occurred in elderly persons and involved mainly newer antidepressants used for non-specific psychiatric symptoms and subthreshold diagnoses, and was associated with indicators of higher clinical complexity or severity and with prescribing without face-to-face patient contact.

Loss of Ovarian Hormones and Accelerated Somatic and Mental Aging.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

Personal, reproductive, and familial characteristics associated with bilateral oophorectomy in premenopausal women: A population-based case-control study.

OBJECTIVES: We investigated the association of personal, reproductive, and familial characteristics with bilateral oophorectomy performed for nonmalignant indications in a US population. STUDY DESIGN: In an established cohort study, we used the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org) to identify 1653 premenopausal women who underwent bilateral oophorectomy in Olmsted County, Minnesota between 1988 and 2007 for a nonmalignant indication. Each woman was matched by age (±1 year) to a population-based referent woman who had not undergone bilateral oophorectomy as of the index date. We used case-control analyses to investigate several characteristics associated with bilateral oophorectomy. Odds ratios and their 95% confidence intervals were adjusted for race, education, and income. RESULTS: In the overall analyses, infertility was more common in women who underwent bilateral oophorectomy than in the controls, whereas use of oral contraceptives, a history of breast feeding, and fibrocystic breast disease were less common. The women who underwent bilateral oophorectomy weighed more than controls, had a higher body mass index and were younger at menarche. The associations were more pronounced for women who underwent the bilateral oophorectomy before age 46 years, and some associations were different for women with or without a benign ovarian indication. Reported family histories of uterine and other cancers were more common in women without a benign ovarian indication. CONCLUSIONS: We identified a number of personal, reproductive, and familial characteristics that were associated with bilateral oophorectomy over a 20-year period. Our historical findings may help inform decision-making about oophorectomy in the future.

Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy.

OBJECTIVE: We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause. DESIGN: We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006. RESULTS: Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk. CONCLUSIONS: Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.