Grossardt, Brandon R.

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.

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.

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.

Background: Apical hypertrophic cardiomyopathy (apical HCM) is a less common subtype of HCM characterized by a focal thickening in the left ventricular apex. “Classic” ECG features have been described, however, apical HCM can persist for many years without detection. We investigated the relationship between ECG findings and echocardiographic morphometry in a large referral series of patients with apical HCM. Methods: We enumerated all patients diagnosed with apical HCM prior to Sept. 30, 2006 using the Mayo Clinic HCM database. We compared echocardiographic measures separately for patients with positive status for two ECG indices of left ventricular hypertrophy (LVH); the Sokolow-Lyon index and the Romhilt-Estes (RE) point-score. We also compared echocardiographic measurements in patients with and without negative T-waves in the precordial leads. Results: Apical HCM was detected in 177 patients (111 men and 68 women). Only 51% had positive Sokolow criteria and 51% had positive RE criteria. The agreement between Sokolow and RE status was high (agreement = 75.0%; kappa = 0.50; 95% CI = 0.38 – 0.62). In particular, Sokolow positive patients had increased LV ejection fraction (P = 0.02), and decreased LV end-systolic diameter (P = 0.03) compared with Sokolow negative patients. The prevalence of right atrial enlargement (47 vs. 28%; P = 0.02) and intracavity obstruction (22 vs. 8%; P = 0.01) were more common in Sokolow positive patients. Positive RE criteria was associated with a greater thickness of the basal septal and basal posterior walls (P = 0.001 and 0.02, respectively), and with a higher frequency of intracavity obstruction (21 vs. 9%; P = 0.04). Most patients (89%) exhibited at least one negative T-wave in the precordial leads; however, only 10% of patients had a negative T-wave of greater than 1.0 mV. We found that patients with an inverted T-wave larger than 0.4 mV (median) had a significantly increased LV ejection fraction (P = 0.03) compared with patients who had smaller or no negative T-waves. Conclusions: Among patients with apical HCM, nearly half do not have ECG evidence of LVH based on classic criteria and most do not have marked T-wave inversions. However, the majority did have at least a mild expression of negative T-waves.

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.

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.

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.

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.