Increased Risk of Multimorbidity in Patients With Sarcoidosis: A Population-Based Cohort Study 1976 to 2013

Objective

To evaluate the risk and pattern of multimorbidity in patients with sarcoidosis.

Cumulative Doses of Ionizing Radiation From Computed Tomography: A Population-Based Study

ObjectiveTo assess cumulative radiation doses from computed tomography (CT), patient characteristics, and clinical indications for CT in a population-based sample.Patients and MethodsA cohort study using medical records linkage through the Rochester Epidemiology Project was conducted to ascertain all CT examinations in Olmsted County, Minnesota, performed between January 1, 2004, and December 31, 2013, among all adults who were alive for 3 or more years after the end of follow-up (to exclude exposures preceding death). Ten-year cumulative effective ionizing radiation doses were estimated on the basis of typical doses per CT modality. Among patients with high doses (≥100 mSv/10 years), CT scans were reviewed for clinical setting, indications, and results.ResultsOf 54,447 adults (median age, 44.0 years at inclusion), 26,377 (48.4%) underwent at least one CT. Ten-year radiation doses from CT were 0.1 to 9.9 mSv in 15.8% of the population (8593 patients), 10 to 24.9 mSv in 16.9% (9502), 25 to 99.9 mSv in 13.8% (7492), and 100 mSv or greater in 1.9% (1041). Computed tomography of the abdomen and pelvis accounted for 67.2% of the estimated dose. In multivariable models, doses differed 1.21-fold to 2.16-fold between extreme categories of age, body mass index, education level, smoking status, and by race. Of 600 CTs in 200 patients with high doses, 70.5% were obtained for restaging of solid cancers and lymphoma, abdominal pain, infection, kidney stones, follow-up of nodules or masses, and chest pain/evaluation for pulmonary embolism.ConclusionExposure to ionizing radiation from CT occurred disproportionally in specific subgroups of the population. A limited number of clinical indications contributed the majority of radiation among adults with high doses.     

Serum 25-Hydroxyvitamin D Values and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort Study

Objective

To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and all-cause and cause-specific mortality.

Health Literacy and Outcomes in Patients With Heart Failure: A Prospective Community Study

Objective

To examine the impact of health literacy on hospitalizations and death in a population of patients with heart failure (HF).

Risk of Cardiovascular Disease and Venous Thromboembolism Among Patients With Incident ANCA-Associated Vasculitis: A 20-Year Population-Based Cohort Study

Objective

To assess the cardiovascular disease (CVD) and venous thromboembolism (VTE) risks among patients with newly diagnosed antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).

A Population-Based Study of the Incidence of Burning Mouth Syndrome

ObjectiveTo calculate the incidence of burning mouth syndrome (BMS) in Olmsted County, Minnesota, from 2000 through 2010.Patients and MethodsBy using the medical record linkage system of the Rochester Epidemiology Project, we identified newly diagnosed cases of BMS from January 1, 2000, through December 31, 2010. Diagnoses were confirmed through the presence of burning pain symptoms of the oral mucosa with normal oral examination findings and no associated clinical signs. Incidence was estimated using decennial census data for Olmsted County.ResultsIn total, 169 incident cases were identified, representing an annual age- and sex-adjusted incidence of BMS of 11.4 per 100,000 person-years. Age-adjusted incidence was significantly higher in women than in men (18.8 [95% CI, 16.4-22.9] per 100,000 person-years vs 3.7 [95% CI, 2.6-5.7] per 100,000 person-years; P<.001). Postmenopausal women aged 50 to 89 years had the highest incidence of the disease, with the maximal rate observed in women aged 70 to 79 years (70.3 per 100,000 person-years). After the age of 50 years, the incidence of BMS in men and women significantly increased across age groups (P=.02). Study participants residing in Olmsted County, Minnesota, were predominantly white, which is a study limitation. In addition, diagnostic criteria for identifying BMS in the present study may not apply for all situations because no diagnostic criteria are universally recognized for identifying BMS.ConclusionTo our knowledge, this is the first population-based incidence study of BMS reported to date. The data reveal that BMS is an uncommon disease highly associated with female sex and advancing age.     

Asthma and Proinflammatory Conditions: A Population-Based Retrospective Matched Cohort Study

ObjectiveTo determine the association between asthma and proinflammatory conditions.Participants and MethodsThis population-based retrospective matched cohort study enrolled all asthmatic patients among Rochester, Minnesota, residents between January 1, 1964, and December 31, 1983. For each asthmatic patient, 2 age-and sex-matched nonasthmatic individuals were drawn from the same population. The asthmatic and nonasthmatic cohorts were followed forward in the Rochester Epidemiology Project diagnostic index for inflammatory bowel disease (IBD), rheumatoid arthritis (RA), diabetes mellitus (DM), and coronary heart disease (CHD) as outcome events. Data were fitted to Cox proportional hazards models.ResultsWe identified 2392 asthmatic patients and 4784 nonasthmatic controls. Of the asthmatic patients, 1356 (57%) were male, and mean age at asthma onset was 15.1 years. Incidence rates of IBD, RA, DM, and CHD in nonasthmatic controls were 32.8, 175.9, 132.0, and 389.7 per 100,000 person-years, respectively; those for asthmatic patients were 41.4, 227.9, 282.6, and 563.7 per 100,000 person-years, respectively. Asthma was associated with increased risks of DM (hazard ratio, 2.11; 95% confidence interval, 1.43-3.13; P<.001) and CHD (hazard ratio, 1.47; 95% confidence interval, 1.05-2.06; P=.02) but not with increased risks of IBD or RA.ConclusionAlthough asthma is a helper T cell type 2–predominant condition, it may increase the risks of helper T cell type 1–polarized proinflammatory conditions, such as CHD and DM. Physicians who care for asthmatic patients need to address these unrecognized risks in asthmatic patients.     

Incidence and Temporal Trends of Primary Immunodeficiency: A Population-Based Cohort Study

OBJECTIVE: To determine the incidence and temporal trends of primary immunodeficiency diseases (PIDs) and examine whether an association exists between delayed diagnosis and increased morbidity.PATIENTS AND METHODS: We performed a historical cohort study to describe the epidemiology of PIDs in Olmsted County, Minnesota, during a 31-year period from January 1, 1976, through December 31, 2006, using the Rochester Epidemiology Project. Incidence and trends over time, presence of comorbid conditions, and trends in management were determined.RESULTS: During the 31-year study period, 158 new cases of PIDs were diagnosed, with an overall incidence rate of 4.6 per 100,000 person-years. The rate of PIDs from 2001 through 2006 (10.3 per 100,000 person-years) was nearly 5 times higher than that from 1976 through 1980 (2.4 per 100,000 person-years). The associations between continuous variable(s) and categorical outcome(s) were assessed by using the Wilcoxon rank sum test. Longer delay in diagnosis was significantly associated with recurrent sinusitis (P<.001), recurrent pneumonia (P=.03), and subsequent treatment with immunoglobulins (P<.001). On the basis of Kaplan-Meier survival estimates, the proportion of patients surviving at 10 years after diagnosis was 93.5% (95% confidence interval, 85.9%-97.1%). However, older age at diagnosis was significantly associated with mortality (P=.01).CONCLUSION: This is one of the first population-based studies to examine the temporal trends of PIDs. The incidence of PIDs increased markedly between 1976 and 2006. In this cohort, a delay in diagnosis was common and was associated with increased morbidity. Despite substantial morbidity, most patients with PIDs can expect a normal life span.CI = confidence interval; PID = primary immunodeficiency diseasePrimary immunodeficiency diseases (PIDs) are a class of disorders in which there is an intrinsic defect in the human immune system. Although PIDs are often described as rare disorders, the true incidence and prevalence of these diseases, either individually or in aggregate, are unknown.¹As the field of PID research continues to expand and newer molecular defects are recognized,^2-4 the impetus is growing for a newborn screen for PIDs, especially severe combined immunodeficiency.^5-7 We need estimates of the incidence and prevalence of the disease in the population to determine the cost-effectiveness of routine screening. Some estimates have been made of the incidence and prevalence of PIDs based on PID registries in various countries^8-13; however, the incidence of PIDs in the United States is unknown. Boyle and Buckley¹ conducted a telephone interview study by random-digit dialing to evaluate the prevalence of PIDs in 2006-2007, but the numbers are approximate and may not correspond to the true incidence and prevalence of PIDs in the population. Our objectives in this study were to (1) describe the epidemiology of PIDs in a defined population in Olmsted County, Minnesota, during a 31-year period using the Rochester Epidemiology Project and (2) evaluate factors associated with morbidity and mortality in the long-term care of patients with PIDs.     

Increasing Incidence of Melanoma Among Middle-Aged Adults: An Epidemiologic Study in Olmsted County,Minnesota

ObjectiveTo identify changes in the incidence of cutaneous melanoma over time in the fastest-growing segment of the US population—middle-aged adults.Patients and MethodsBy using the Rochester Epidemiology Project resource, we identified patients aged 40 to 60 years who had a first lifetime diagnosis of melanoma between January 1, 1970, and December 31, 2009, in Olmsted County, Minnesota. The incidence of melanoma and overall and disease-specific survival rates were compared by age, sex, year of diagnosis, and stage of disease.ResultsBetween 1970 and 2009, age- and sex-adjusted incidence increased significantly over time (P<.001) from 7.9 to 60.0 per 100,000 person-years, with a 24-fold increase in women and a 4.5-fold increase in men. Although not significant (P=.06), the incidence of melanoma increased with age. Overall and disease-specific survival improved over time, with hazard ratios of 0.94 (P<.001) and 0.93 (P<.001) for each 1-year increase in the year of diagnosis, respectively. Each 1-year increase in the age at diagnosis was associated with an increased risk of death from any cause (hazard ratio, 1.07; P=.01) but was not significantly associated with disease-specific death (P=.98). Sex was not significantly associated with death from any cause (P=.81) or death from disease (P=.23). No patient with malignant melanoma in situ died from disease. Patients with stage II, III, and IV disease were more than 14 times more likely to die from disease than were patients with stage 0 or I disease (P<.001).ConclusionThe incidence of cutaneous melanoma among middle-aged adults increased over the past 4 decades, especially in middle-aged women, whereas mortality decreased.     

Weren't Asked,Didn't Tell: Prevalence of Communication of Suicidal Ideation in Suicide Decedents During the Last Year of Life

Objective

To explore what percentage of suicide decedents (SDs) vs controls were assessed for suicidality at medical appointments in the year before death.

Serum 25-Hydroxyvitamin D and Subsequent Cancer Incidence and Mortality: A Population-Based Retrospective Cohort Study

ObjectiveTo determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and subsequent cancer incidence and mortality.Patients and MethodsWe identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, who had at least 1 25(OH)D measurement and no prior diagnosis of cancer. Cancer outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients’ final clinical visit as an Olmsted County resident; December 31, 2014; or death. Cox proportional hazards regression was used to analyze data.ResultsA total of 8700 individuals had a 25(OH)D measurement and no history of cancer, with a mean ± SD 25(OH)D value of 29.7±12.8 ng/mL (to convert to nmol/L, multiply by 2.496). The mean ± SD age was 51.5±16.4 years, and most were women (78.1%; n=6796) and White (85.7%; n=7460). A total of 761 individuals developed cancer (skin cancer, n=360; nonskin cancer, n=401) during a median follow-up of 4.6 (interquartile range, 3.4-6.1) years. Compared with participants with 25(OH)D values of 20 to 50 ng/mL (reference group), those with 25(OH)D values less than 12 ng/mL had a greater nonskin cancer incidence (hazard ratio [HR], 1.56; 95% CI, 1.03 to 2.36; P=.04) after adjustment. There was no association between 25(OH)D values and total cancer or skin cancer incidence. Compared with individuals from the reference group, 25(OH)D levels less than 12 ng/mL (HR, 2.35; 95% CI, 1.01 to 5.48; P=.047) and 12 to 19 ng/mL (HR, 2.10; 95% CI, 1.05 to 4.22; P=.04) were associated with increased cancer mortality.ConclusionLow 25(OH)D levels were associated with increased risk for incident nonskin cancer and cancer-related mortality.     

Osteoporosis and Fractures After Solid Organ Transplantation: A Nationwide Population-Based Cohort Study

ObjectiveTo investigate the incidence of bone disorders after solid organ transplantation (SOT).Participants and MethodsWe used Taiwan's National Health Insurance Research Database to identify 9428 recipients of SOT and 38,140 sex- and age- matched control subjects between January 1, 1997, and December 31, 2010, to compare the incidence and risk of bone disorders between groups.ResultsRecipients of SOT had a significantly higher incidence of osteoporosis and related fractures compared with the non-SOT group. The overall hazard ratio (HR) of osteoporosis after SOT was 5.14 (95% CI, 3.13-8.43), and the HR of related fractures was 5.76 (95% CI, 3.80-8.74). The highest HRs were observed in male patients (HR, 7.09; 95% CI, 3.09-16.3) and in those aged 50 years or younger (HR, 7.38; 95% CI, 2.46-22.1). In addition, SOT patients without any comorbidities had a 9.03-fold higher risk of osteoporosis than non-SOT participants (HR, 9.03; 95% CI, 5.29-15.4). To compare the risk of osteoporosis and related fractures in different recipients of SOT, the highest risk of osteoporosis and fractures was noted in patients receiving lung transplantation, followed by other types of SOT.ConclusionWe report high rates of metabolic bone disorders after SOT in chronic transplant patients over a long follow-up. Both underlying bone disorders before transplantation and use of immunosuppressant agents may contribute to bone disorders after transplantation.     

High School Football and Late-Life Risk of Neurodegenerative Syndromes, 1956-1970

Objective

To assess whether athletes who played American varsity high school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life.

The Epidemiology of Skin and Skin-Related Diseases: A Review of Population-Based Studies Performed by Using the Rochester Epidemiology Project

In Olmsted County, Minnesota, population-based epidemiologic research studies are possible because of a unique medical records linkage system, the Rochester Epidemiology Project (REP), which has been in place for almost half a century. We present a summary of epidemiologic data describing the incidence of skin diseases derived from the REP. Since 1966, more than 2000 articles have been published by the REP team. Each published article was reviewed by both authors in conjunction with the REP team to select all articles that described the incidence of skin and selected skin-related diseases. Collectively, these reports suggested that the incidence of most of the studied skin diseases has increased over the decades.     

Electronic Algorithm Is Superior to Hospital Discharge Codes for Diagnoses of Hypertensive Disorders of Pregnancy in Historical Cohorts

Objectives

To develop and validate criteria for the retrospective diagnoses of hypertensive disorders of pregnancy that would be amenable to the development of an electronic algorithm, and to compare the accuracy of diagnoses based on both the algorithm and diagnostic codes with the gold standard, of physician-made diagnoses based on a detailed review of medical records using accepted clinical criteria.

Breast Cancer Mode of Detection in a Population-Based Cohort

ObjectiveTo evaluate how breast cancers come to clinical attention (mode of detection [MOD]) in a population-based cohort, determine the relative frequency of different MODs, and characterize patient and tumor characteristics associated with MOD.Patients and MethodsWe used the Rochester Epidemiology Project to identify women ages 40 to 75 years with a first-time diagnosis of breast cancer from May 9, 2017, to May 9, 2019 (n=500) in a 9-county region in Minnesota. We conducted a retrospective medical record review to ascertain the relative frequency of MODs, evaluating differences between screening mammography vs all other MODs by breast density and cancer characteristics. Multiple logistic regression was conducted to examine the likelihood of MOD for breast density and stage of disease.ResultsIn our population-based cohort, 162 of 500 breast cancers (32.4%) were detected by MODs other than screening mammography, including 124 (24.8%) self-detected cancers. Compared with women with mammography-detected cancers, those with MODs other than screening mammography were more frequently younger than 50 years of age (P=.004) and had higher-grade tumors (P=.007), higher number of positive lymph nodes (P<.001), and larger tumor size (P<.001). Relative to women with mammography-detected cancers, those with MODs other than screening mammography were more likely to have dense breasts (odds ratio, 1.87; 95% CI, 1.20 to 2.92; P=.006) and advanced cancer at diagnosis (odds ratio, 3.58; 95% CI, 2.29 to 5.58; P<.001).ConclusionOne-third of all breast cancers in this population were detected by MODs other than screening mammography. Increased likelihood of nonmammographic MODs was observed among women with dense breasts and advanced cancer.     

Comparing Cardiovascular Safety of Febuxostat and Allopurinol in the Real World: A Population-Based Cohort Study

ObjectiveTo determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use.Patients and MethodsWe conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined.ResultsA total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner.ConclusionThe use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes.     

Association of Statin Use With Mortality After Dialysis-Requiring Acute Kidney Injury: A Population-Based Cohort Study

Objective

To investigate the association between statin use and mortality in patients with dialysis-requiring acute kidney injury (AKI-D).