Medical Records Linkage System Research Articles

Population-Based Incidence and Clinical Characteristics of Ocular Adnexal Tumors in Olmsted County, Minnesota

ABSTRACT Purpose To determine the incidence and clinical characteristics of ocular adnexaltumors in Olmsted County, Minnesota. Methods Retrospective population-based cohort study of all patients residing in Olmsted County, Minnesota diagnosed with any ocular tumor from January 1, 2006, to December 31, 2015. The medical records of all patients with an incident diagnosis of any ocular adnexal tumor were reviewed using the Rochester Epidemiology Project medical record linkage system for patient demographics, tumor type, and histopathologic confirmation. Incidence rates were calculated per 100,000 person-years. Poisson regression analysis was used to analyze changes in incidence over time. Results There were 717 patients diagnosed with ocular adnexal tumors during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 59.7 per 100,000 (95% CI 55.4 to 64.0, p < 0.05) per year. In total, 764 tumors were diagnosed. Most tumors were eyelid lesions (N = 756, 99.0%), which were mostly benign (N = 512, 67.8%) with epidermal inclusion cysts (N = 275, 36.0%), hidrocystoma (N = 70, 9.2%), and eyelid sebaceous cysts (N = 46, 6.1%) accounting for the majority. Malignant eyelid lesions (N = 244, 31.9%) were relatively common with basal cell carcinoma (N = 184, 24.1%) and squamous cell carcinoma (N = 49, 6.4%) having the highest frequencies. Orbital tumors (N = 8, 1.0%) were infrequent. Of the orbital tumors, the most common was lacrimal gland adenoidcystic carcinoma (N = 2, 25.0%). Conclusions In a population-based setting, most ocular adnexal tumors were benign eyelid lesions. Understanding the epidemiology of ocular adnexal tumors is important to aid providers in diagnosing and facilitating appropriate referrals of potentially vision- and life-threatening malignancies.

Trends in the 30-year span of noninfectious cardiovascular implantable electronic device complications in Olmsted County

Cardiac implantable electronic devices (CIEDs), such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. We sought to describe trends in noninfectious CIED complications over the past 3 decades in Olmsted County. The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966 to present. CIED implantations between 1988 and 2018 were determined. Trends in noninfectious complications within 30 days of implantation were analyzed. A total of 157 (6.2%) of 2536 patients who received CIED experienced device complications. A total of 2.7% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.8%), followed by hematoma (1.7%). Complications went up from 1988 to 2005, and then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (P < .01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity index has trended up over the 30 years. Our study describes a real-world trend of CIED complications over 3 decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.

Disparities in Influenza, Pneumococcal, COVID-19 Vaccine Coverage in High-Risk Adults Aged 19 to 64 Years in Southeastern Minnesota, 2010-2021

Despite effective vaccines against influenza, pneumococcus, and COVID-19, uptake has been suboptimal. Although disparities in vaccination by race and ethnicity have been observed, what is the role of other sociodemographic factors in US vaccine uptake? We conducted a population-based study using the Rochester Epidemiology Project (REP), a comprehensive medical records linkage system, to assess effects of sociodemographic factors including race, ethnicity, individual-level socioeconomic status (SES) via the housing-based socioeconomic status index, education, population density (urban or nonurban), and marital status with uptake of influenza, pneumococcal, and COVID-19 vaccination in high-risk adults. Adults at high risk of invasive pneumococcal disease residing in four counties in southeastern Minnesota who were aged 19 to 64 years were identified. Vaccination data were obtained from the Minnesota Immunization Information Connection and REP from January 1, 2010, through December 31,2021. We identified 45,755 residents. Most were White (82%), non-Hispanic (94%), married (56%), and living in an urban setting (81%), with three-quarters obtaining at least some college education (74%). Although 45.1%were up to date on pneumococcal vaccines, 60.1%had completed the primary COVID-19 series. For influenza and COVID-19, higher SES, living in an urban setting, older age, and higher education positively correlated with vaccination. Magnitude of differences in race, education, and SES widened with booster vaccines. This high-risk population is undervaccinated against preventable respiratory diseases, especially influenza and pneumococcus. Although national data reported improvement of disparities in COVID-19 vaccination uptake observed early in the pandemic, our data demonstrated gaps related to race, education level, SES, and age that widened with booster vaccines. Communities with high social vulnerabilities often show increased risk of severe disease outcomes, yet demonstrate lower uptake of preventive services. This highlights the need to understand better vaccine compliance and access in rural, lower SES, less-educated, Black, Hispanic, and younger populations, each of which were associated independently with decreased vaccination.

Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals

IntroductionEnlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls. MethodsThirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated. ResultsBoth iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03). ConclusionsFewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance.

Association of Anxiety and Unspecified Emotional Distress Obtained from a Medical Records Linkage System with Incident Cognitive Outcomes in a Population-Based Setting.

Studies that assess cognition prospectively and study in detail anxiety history in the participants' medical records within the context of brain aging and Alzheimer's disease are limited. To examine the associations of anxiety and unspecified emotional distress (UED) acquired throughout a person's life with prospectively collected cognitive outcomes. Mayo Clinic Study of Aging participants who were cognitively unimpaired at baseline were included. Anxiety and UED data were abstracted from the medical record using the Rochester Epidemiology Project (REP) resources and were run separately as predictors in our models. The data were analyzed using Cox proportional hazards models for the outcomes of incident mild cognitive impairment (MCI) and dementia and using linear mixed effects models for the outcomes of global and domain specific cognitive z-scores and included key covariates. The study sample (n = 1,808) had a mean (standard deviation) age of 74.5 (7.3) years and 51.4% were male. Anxiety was associated with increased risk of MCI and dementia and was associated with lower baseline cognitive z-scores and accelerated decline over time in the global, memory, and attention domains. UED was associated with faster decline in all domains except visuospatial but did not show evidence of association with incident cognitive outcomes. These results varied by medication use and timing of anxiety. Anxiety and UED both showed inverse associations with cognition. Utilization of anxiety and UED data from across the life course, as available, from the REP system adds robustness to our results.

Neuropsychiatric symptoms and risk of cognitive impairment: Mayo Clinic Study of Aging

AbstractBackgroundMost studies on the relationship between neuropsychiatric symptoms (NPS) and cognitive decline focus on NPS data collected over a short period of time. To better understand the association between NPS and cognitive decline, including their temporal relationship, it is important to know NPS status across a person’s life.MethodWe utilized the unique Rochester Epidemiology Project medical record linkage system that has captured medical records as far back as 1907, to abstract the psychiatric history of 1810 cognitively unimpaired participants in the population‐based Mayo Clinic Study of Aging (MCSA). Trained nurse abstractors ascertained the presence of exposure to three common NPS (anxiety, depression, and unspecified emotional distress [UED]), both before and after entry into the MCSA. We conducted Cox Proportional Hazards (PH) models using age as the time scale and adjusting for sex, education, and APOE E4 allele for each NPS in predicting mild cognitive impairment (MCI), or dementia. Additional analyses considering medication use (yes/no) and timing of NPS were also run.ResultAnxiety (Hazard Ratio [HR] = 1.47, p&lt;0.001), depression (HR = 1.36, p = 0.001), and UED (HR = 1.22, p = 0.039) were associated with a higher risk of MCI. These associations were present regardless of medication use for anxiety (With medication: HR = 1.51, p&lt;0.001; without medication: HR = 1.41, p = 0.015), and for those taking medications for depression (With medication: HR = 1.47, p&lt;0.001; without medication: 1.09, p = 0.597). Anxiety was associated with MCI regardless of timing of onset with the strongest relationship being for those with onset of anxiety before 65 that persisted into later life (HR = 1.88, p = 0.004). Depression was associated regardless of timing of onset if the depression was present in late life too. The results were similar for the outcome of dementia (Anxiety: HR = 1.62, p&lt;0.001; depression: HR = 1.31, p = 0.040; UED: HR = 1.37, p = 0.014). The associations accounting for medication use and timing of NPS were similar for the outcome of dementia too.ConclusionNPS is associated with progression to MCI and dementia. Both medication use and timing of NPS might play a role in these associations.

Racial differences in pathways to care preceding first episode mania or psychosis: a historical cohort prodromal study.

There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients. Using a comprehensive medical records linkage system (Rochester Epidemiology Project, REP), we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White). A total of 205 (FEM = 74; FEP = 131) incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; p < 0.001) with an older age at time of first visit for a mental health complaint (15.7 ± 6.3 vs. 11.1 ± 6.0 years; p = 0.005). There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use. These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies.

Choroidal Nevus Features Associated with Subspecialty Referral

To identify choroidal nevus features associated with referral to a retina or ocular oncology subspecialist. Population-based retrospective cohort study. Patients diagnosed with choroidal nevus. Population-based retrospective cohort study of residents of Olmsted County, Minnesota, with an incident diagnosis of choroidal nevus from January 1, 2006, to December 31, 2015 using the Rochester Epidemiology Project, a medical record linkage system. Tumor features and patient demographics associated with referral to a retina or ocular oncology subspecialist were assessed. Wilcoxon rank sum test, chi-square test, and Fisher exact test were used for statistical analysis. Tumor features and patient demographics associated with referral to subspecialty care. There were 826 incident diagnoses of choroidal nevus, of which 88 cases (11%) were referred, with highest level of referral being retina in 29 cases (33%) and ocular oncology in 59 cases (67%). None of the analyzed demographic features were associated with choroidal nevus referral to subspecialty care. Tumor features associated with referral (vs. not referred) included greater mean basal diameter (4.6 mm vs. 2.4 mm, P<0.001), greater mean tumor thickness (0.7 mm vs. 0.1 mm, P < 0.001), greater distance to optic disc (6.9 mm vs. 3.4 mm, P= 0.02), halo around nevus (5.7% vs. 0.4%, P < 0.001), and drusen on OCT (51% vs. 25%, P=0.002). Presence of orange pigment (8% vs. 0%, P= 0.14), subretinal fluid (9% vs. 2.5%, P= 0.09), and low internal reflectivity on A-scan (7.7% vs. 0%, P= 1.00) were not found more frequently in the subspecialty referral group. Greater basal diameter and mean tumor thickness of choroidal nevus were associated with referral to retina or ocular oncology. However, several features associated with increased risk of malignant transformation were not associated with subspecialty referral. These findings highlight the importance of educating eye care providers about high-risk tumor features associated with choroidal nevus transformation to melanoma. In the primary eye care setting where not all multimodal imaging may be available, we encourage color photography and OCT with referral for any features of basal diameter > 5 mm, presence of subretinal fluid, or thickness too large for capture by enhanced-depth imaging OCT. The authors have no proprietary or commercial interest in any materials discussed in this article.

The incidence of periocular melanoma: An epidemiologic study in Olmsted County, Minnesota

To the Editor: Melanoma arising in the periocular area presents a unique treatment challenge due to anatomic and functional constraints. To date, most information regarding periocular melanoma is gleaned from extrapolated data from other sites of the body, assuming similar biologic behavior. We aimed to identify the overall incidence, pathologic features, and surgical outcomes of periocular melanoma. Following Institutional Review Board (IRB) approval, using the Rochester Epidemiology Project (a multicenter medical records–linkage system encompassing the Olmsted County population), we identified patients with a first lifetime diagnosis of periocular melanoma between January 1, 1970, and December 31, 2020, while a local resident of Olmsted County, Minnesota. Outside (nonresident) referral cases were excluded. Periocular melanoma was defined as a melanoma arising within the orbital rim – on the upper or lower eyelid, lateral canthus, or eyebrow. A total of 10 patients with primary periocular melanoma were identified. The overall incidence rate of periocular melanoma was 0.2686 per 100,000 patient-years. Among all melanomas diagnosed during that timeframe in Olmsted County, 0.43% were periocular in location. No cases extended onto conjunctiva. The histogenic subtype was lentigo maligna in 8 (80.0%). There was 1 superficial spreading melanoma and 1 case without documentation of histogenic subtype. Incidence of in situ (50.0%) and invasive (50.0%) melanomas was equal. Among invasive melanomas, the average Breslow depth was 0.90 mm (range, 0.2-2.6 mm). Seven (70.0%) were treated with Mohs micrographic surgery (MMS). One (10%) was treated with wide local excision. The 2 cases that did not undergo further surgical treatment were both diagnosed prior to 2000 and were removed entirely via initial excisional biopsy. There was 1 regional metastasis to the parotid gland and lymph node, 2.5 years after diagnosis of a superficial spreading melanoma, Breslow 0.7 mm, status-post treatment with MMS. There were no other local or distant recurrences. There were no melanoma-specific deaths. Mean follow-up time was 7.4 years (range 3.1-13.2). This study demonstrates the relative rarity of periocular melanoma, comprising only 0.43% of all melanomas. Comparatively, basal cell carcinoma (BCC) occurs on the eyelid 16% of the time.1Salomon J. Bieniek A. Baran E. Szepietowski J.C. Basal cell carcinoma on the eyelids: own experience.Dermatol Surg. 2004; 30: 257-263PubMed Google Scholar Our study found an overall periocular melanoma incidence rate of 0.2686 per 100,000 patient-years. A previous Olmsted County cohort reported an incidence of eyelid BCC as 14.35 per 10,000 individuals per year, and an incidence of eyelid SCC as 1.37 cases per 100,000 individuals per year.2Cook Jr., B.E. Bartley G.B. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota.Ophthalmology. 1999; 106: 746-750Abstract Full Text Full Text PDF PubMed Google Scholar The behavior of melanoma seems to parallel primary cutaneous melanoma of head and neck sites. Most tumors were associated with chronic sun exposure; 80% of cases were lentigo maligna subtype. There was 1 regional recurrence in our study, no distant recurrences, and no deaths due to melanoma. The most significant advantage of our study is in its epidemiologic design. The limitations of this study include the retrospective nature of our analysis and the homogenous demographics of Olmsted County, comprised of mostly Caucasian individuals of higher socioeconomic status.3St Sauver J.L. Grossardt B.R. Leibson C.L. Yawn B.P. Melton 3rd, L.J. Rocca W.A. Generalizability of epidemiological findings and public health decisions: an illustration from the Rochester Epidemiology Project.Mayo Clin Proc. 2012; 87: 151-160Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar Additionally, some melanomas may have been missed if the tumor was initially labeled as another anatomic site (cheek, nose, temple, etc.) and had extension onto the lid proper. None disclosed. We would like to acknowledge Austin Todd, MS, for his assistance in statistical analysis.

PO-05-046 TRENDS IN NON-INFECTIOUS CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE COMPLICATIONS OVER THIRTY YEARS: INSIGHTS FROM THE ROCHESTER EPIDEMIOLOGY PROJECT DEVICE REGISTRY

Cardiovascular implantable electronic devices (CIEDs) such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. Describe trends in non-infectious CIED complications over the past three decades in Olmsted County. The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966-current. CIED implants between 1988-2018 were determined. Trends in non-infectious complications within 30 days of implant were analyzed. A total of 194 complications were noted in 2536 patients. Lead dislodgement was the most common (3.0%), followed by hematoma (2.1%). Complications went up from 1988 to 2005, then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (p<0.01). Those with complications were noted to have more valvular disease and greater mortality. The Charlson comorbidity score went up until 2011 and then trended down. Trends for specific complications are elucidated in the Figure. Our study describes a real-world trend of CIED complications over three decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade, likely owing to safer practices and better understanding of anticoagulant management.

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.

Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort

ObjectiveTo examine the associations between antidepressant exposure during the third trimester of pregnancy, including individual drugs, drug doses, and antidepressant combinations, and the risk of poor neonatal adaptation (PNA). Patients and MethodsThe Rochester Epidemiology Project medical records-linkage system was used to study infants exposed to selective serotonin reuptake inhibitors (SSRIs; n=1014), bupropion, (n=118), serotonin-norepinephrine reuptake inhibitors (n=80), antidepressant combinations (n=20), or other antidepressants (n=22) during the third trimester (April 11, 2000-December 31, 2013). Poor neonatal adaptation was defined based on a review of medical records. Poisson regression was used to examine the risk of PNA with serotonergic antidepressant and drug combinations compared with that with bupropion monotherapy as well as with high- vs standard-dose antidepressants. When possible, analyses were performed using propensity score (PS) weighting. ResultsForty-four infants were confirmed cases of PNA. Serotonin-norepinephrine reuptake inhibitor monotherapy, antidepressant combinations, and paroxetine monotherapy were associated with a significantly higher risk of PNA than bupropion monotherapy in unweighted analyses. High-dose SSRI exposure was associated with a significantly increased risk of PNA in unadjusted (relative risk, 2.61; 95% confidence interval, 1.35-5.04) and PS-weighted models (relative risk, 2.29; 95% confidence interval, 1.17-4.48) compared with standard-dose SSRI exposure. The risk of PNA was significantly higher with high-dose paroxetine and sertraline than with standard doses in the PS-weighted analyses. The other risk factors for PNA included maternal anxiety disorders. ConclusionAlthough the frequency of PNA in this cohort was low (3%-4%), the risk of PNA was increased in infants exposed to serotonergic antidepressants, particularly with SSRIs at higher doses, during the third trimester of pregnancy compared with that in infants exposed to standard doses. Potential risk factors for PNA also included third-trimester use of paroxetine (especially at higher doses) and maternal anxiety.

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

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. 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. 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). 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.

Frequency and type of premature or early menopause in a geographically defined American population

ObjectiveThere is limited information on the prevalence of premature and early menopause. Therefore, we studied the frequency and type of premature (age < 40 years) or early (age 40–44 years) menopause in a geographically-defined American population. MethodsWe studied a random sample of women aged 18 to 50 years who resided in Olmsted County, MN between 1988 and 2007. Women were followed through December 2021, and age at cessation of menses was assessed via review of the medical records included in a medical records-linkage system. Menopause was defined as cessation of menses due to spontaneous or induced ovarian insufficiency. Results1015 women (71.3 %) underwent spontaneous menopause, 138 (9.7 %) underwent bilateral oophorectomy, 17 (1.2 %) had antecedent chemotherapy or radiation therapy, and 254 (17.8 %) underwent hysterectomy or endometrial ablation. The median age at cessation of menses was 51.0 years (IQR, 49.0–52.0) for spontaneous menopause, 46.0 years (IQR, 41.0–49.0) for menopause induced by oophorectomy, chemotherapy, or radiation therapy, and 38.0 years (IQR, 33.0–44.0) for hysterectomy. Considering both spontaneous and induced menopause, the frequency was 3.1 % (95 % CI, 2.2–4.2) for premature and 6.2 % (95 % CI, 5.0–7.8) for early menopause. Considering only spontaneous menopause, the frequency reduced to 0.4 % (95 % CI, 0.2–1.0) for premature and 5.2 % (95 % CI, 4.0–6.8) for early menopause. However, considering all types of cessations of menses, the frequency was 12.2 % (95 % CI, 10.6–14.0) for premature and 9.7 % (95 % CI, 8.3–11.3) for early cessation of menses. DiscussionApproximately 3 % of women in the general population experienced either spontaneous or induced premature menopause. The most common cause of premature menopause was bilateral oophorectomy.

Disparities in vaccination rates in solid organ transplant patients.

Vaccinations against preventable respiratory infections such as Streptococcus pneumoniae and influenza are important in immunosuppressed solid organ transplant (SOT) recipients. Little is known about the role of age, race, ethnicity, sex, and sociodemographic factors including rurality, or socioeconomic status (SES) associated with vaccine uptake in this population. We conducted a population-based study using the Rochester Epidemiology Project, a medical records linkage system, to assess socioeconomic and demographic factors associated with influenza and pneumococcal vaccination rates among adult recipients of solid organ transplantation (aged 19-64 years) living in four counties in southeastern Minnesota. Vaccination data were obtained from the Minnesota Immunization Information Connection from June 1, 2010 to June 30, 2020. Vaccination rate was assessed with Poisson and logistic regression models. A total of 468 SOT recipients were identified with an overall vaccination rate of 57%-63% for influenza and 56% for pneumococcal vaccines. As expected, vaccination for pneumococcal vaccine positively correlated with influenza vaccination. Rural patients had decreased vaccination in both compared to urban patients, even after adjusting for age, sex, race, ethnicity, and SES. Although the population was mostly White and non-Hispanic, neither vaccination differed by race or ethnicity, but influenza vaccination did by SES. Among organ transplant groups, liver and lung recipients were least vaccinated for influenza, and heart recipients were least up-to-date on pneumococcal vaccines. Rates of vaccination were below national goals. Rurality was associated with undervaccination. Further investigation is needed to understand and address barriers to vaccination among transplant recipients.

Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD. We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R 2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance. Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.

Convergence of four measures of multi-morbidity.

To compare the agreement between percentile ranks from 4 multi-morbidity scores. Population-based descriptive study. Olmsted County, Minnesota (USA). 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). 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). 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. 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 between hearing loss and development of dementia using formal behavioural audiometric testing within the Mayo Clinic Study of Aging (MCSA): a prospective population-based study

Hearing loss has been identified as a potential major modifiable risk factor for developing dementia. This study examined associations between formal behavioural pure-tone and speech audiometry assessed by an audiologist with development of dementia in the Mayo Clinic Study of Aging (MCSA). The MCSA is a prospective population-based study examining the incidence, prevalence, and risk factors of mild cognitive impairment and dementia in Olmsted County, Minnesota, USA. Participants undergo clinical examinations with neuropsychological testing at enrolment and every 15 months. Participants were 50 years or older at enrolment between Nov 29, 2004, and Dec 23, 2019, who underwent formal behavioural audiometric evaluation by an audiologist due to concerns about hearing loss or as a part of annual comprehensive health assessments. Associations of pure-tone average (PTA) and word recognition scores (WRS) with the development of dementia were evaluated using Cox proportional hazards regression with age as the timescale, and associations with changes in cognitive testing scores over time were evaluated using linear mixed-effects models. Among 1200 eligible participants, the mean age at enrolment was 79 years (SD 9), 593 (49%) were men, and 207 developed dementia during a mean of 7·0 years (SD 3·7) of follow-up. After adjusting for sex, years of education, smoking status, diabetes, hypertension, apolipoprotein E ε4 carriership, and hearing rehabilitation (defined as hearing aid or cochlear implant use), neither PTA (hazard ratio [HR] per 10-decibels hearing level increase of 0·99 (95% CI 0·89-1·12; p=0·91) nor WRS (HR per 10% decrease of 0·98, 95% CI 0·89-1 ·07; p=0·65) was significantly associated with the development of dementia. However, both PTA and WRS were significantly associated with poorer performance in cognitive testing over time: participants with a PTA higher than 25 decibels hearing level or a WRS lower than 100% had significantly worse declines in cognitive testing scores. Informant-based hearing difficulties assessed by the participant's study partner were significantly associated with the development of dementia (HR 1·95, 95% CI 1·45-2·62; p<0·0001). In this prospective population-based study, subjective informant-based hearing difficulties were associated with development of dementia, whereas objective measures on formal behavioural audiometry were predictive of poorer performance on cognitive testing over time but not the development of dementia. Other factors related to central processing might potentiate the effects of peripheral hearing loss detected on behavioural audiometric testing. National Institute of Health, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, the GHR Foundation, the Mayo Foundation for Medical Education and Research, the Liston Award, the Schuler Foundation, the Rochester Epidemiology Project medical records linkage system, and the National Institute on Aging.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Association of Premenopausal Bilateral Oophorectomy With Parkinsonism and Parkinson Disease

The association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial. To 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. This 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. Medical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project). Incidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review. Among 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]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; 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. In 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.