Grossardt, Brandon R

Background We examined the relationship between infection‐related hospitalization (IRH) and heart failure (HF) in a large clinical health system and assessed whether IRH improved prediction beyond HF risk equations. Methods We studied 80 880 adults (14 150 with IRH and 66 730 age‐ and sex‐matched comparators) aged ≥18 years without HF in the Rochester Epidemiology Project from 1/1/2005–12/31/2019. IRH was identified using International Classification of Diseases ( ICD ) codes. HF incidence was defined as ≥1 HF‐related ICD code. Multivariable Cox models assessed the association between IRH and incident HF. Among 29 219 adults aged 30 to 79 years without baseline cardiovascular disease in the Rochester Epidemiology Project, Harrell's concordance statistic assessed whether IRH improved discrimination of the Predicting Risk of Cardiovascular Disease EVENTs–Heart Failure (PREVENT‐HF) equations. Results Participants were 53.3% women, 85.6% White individuals, and 95.1% non‐Hispanic individuals, with a mean age of 56.0±20.0 years. Median follow‐up time was 6.2 years. Among the IRH group, 2729 developed incident HF (2.75/100 person‐years) versus 4854 (1.00/100 person‐years) in the comparator. The multivariable adjusted hazard ratio for incident HF among participants with versus without an IRH was 1.85 (95% CI, 1.76, 1.94). In a separate cohort, incorporating IRH into PREVENT‐HF increased the concordance statistic from 0.776 to 0.779 (change, 0.003 [95% CI, 0.001–0.004]). The PREVENT‐HF risk score underestimated the 10‐year risk of HF by up to 9% among participants with an IRH. Conclusions IRH was associated with incident HF but provided negligible change to 10‐year HF risk discrimination. However, among individuals with an IRH, incorporating this information meaningfully improved 10‐year HF risk prediction. Severe infections may serve as a risk‐enhancing factor warranting enhanced preventive measures, particularly in populations where IRH is more common.

INTRODUCTION: A deeper understanding of the factors influencing survival in patients with pancreatic ductal adenocarcinoma (PDAC) is essential for optimizing treatment strategies. This study investigates the independent association of body composition parameters with overall survival in patients with PDAC. METHODS: This retrospective multisite cohort study included patients diagnosed with PDAC. Diagnostic computed tomography scans were retrieved, and body composition was evaluated using a validated deep learning-based segmentation algorithm that measured tissue volume and density in a 20 cm vertical abdominal section. RESULTS: A total of 1,666 patients with PDAC were included, 938 male (56.3%) and median age 69 years (interquartile range 61–76). In the subgroup of patients who underwent surgical resection (n = 509), myosteatosis (intramuscular infiltration of adipose tissue; hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.16–2.11, P = 0.004), sarcopenic obesity (HR 1.75, 95% CI 1.06–2.91, P = 0.03), and less subcutaneous adipose tissue (HR 1.09, 95% CI 1.03–1.16, P = 0.002) were associated with higher mortality. In patients receiving palliative systemic therapy (n = 439), lower skeletal muscle density (HR 1.43, 95% CI 1.03–1.99, P = 0.03) was associated with higher mortality. In patients who did not undergo tumor-targeted treatment (n = 718), less visceral adipose tissue (HR 1.04, 95% CI 1.01–1.08, P = 0.02) was associated with higher mortality. DISCUSSION: Body composition parameters, derived from computed tomography scans at the time of PDAC diagnosis, particularly low skeletal muscle density, sarcopenic obesity, and low adipose tissue, are independently associated with overall survival in patients with PDAC. Evaluating body composition at diagnosis could enhance clinical decision-making and enable more personalized treatment strategies.

Abstract 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.

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 Bilateral oophorectomy has commonly been performed in conjunction with hysterectomy even in women without a clear ovarian indication; however, oophorectomy may have long-term deleterious consequences. To better understand this surgical practice from the woman’s perspective, we studied the possible association of adverse childhood or adult experiences with the subsequent occurrence of bilateral oophorectomy. Design Population-based case–control study. Setting Olmsted County, Minnesota (USA). Participants From an established population-based cohort study, we sampled 128 women who underwent bilateral oophorectomy before age 46 years for a non-cancerous condition in 1988–2007 (cases) and 128 age-matched controls (±1 year). Methods Information about adverse experiences was abstracted from the medical records dating back to age 15 years or earlier archived in the Rochester Epidemiology Project (REP) records-linkage system. Adverse childhood experiences were summarised using the Adverse Childhood Experience (ACE) score. Results We observed an association of bilateral oophorectomy performed before age 46 years with verbal or emotional abuse, physical abuse, any abuse, substance abuse in the household, and with an ACE score ≥1 experienced before age 19 years (OR=3.23; 95% CI 1.73 to 6.02; p<0.001). In women who underwent the oophorectomy before age 40 years, we also observed a strong association with physical abuse experienced during adulthood (OR=4.33; 95% CI 1.23 to 15.21; p=0.02). Several of the associations were higher in women who underwent oophorectomy at a younger age (<40 years) and in women without an ovarian indication for the surgery. None of the psychosocial or medical variables explored as potential confounders or intervening variables changed the results noticeably. Conclusions Women who suffered adverse childhood experiences or adult abuse are at increased risk of undergoing bilateral oophorectomy before menopause. We suggest that the association may be explained by a series of biological, emotional, and psychodynamic mechanisms.

ABSTRACT Background Epidemiological studies of drug‐induced parkinsonism remain limited. Objectives To investigate the incidence and time trends of drug‐induced parkinsonism over 30 years in a geographically defined American population. Methods We used the medical records‐linkage system of the Rochester Epidemiology Project to identify all persons in Olmsted County, Minnesota, who received a screening diagnostic code for parkinsonism from 1976 through 2005. A movement disorders specialist reviewed the complete medical records of each person to confirm the presence of drug‐induced parkinsonism associated with dopamine‐blocking or dopamine‐depleting medications. Results Among 906 incident cases of parkinsonism from 1976 to 2005, 108 persons had drug‐induced parkinsonism (11.9%). The average annual incidence rate of drug‐induced parkinsonism was 3.3 per 100,000 person‐years, was higher in women, and increased with older age. Drug‐induced parkinsonism was the fifth‐most common type of parkinsonism overall; however, it was the most common type among persons younger than age 40 years. Typical antipsychotic drugs were the most common class of drugs associated with parkinsonism, whereas atypical antipsychotic drugs were rarely involved. The incidence rate of drug‐induced parkinsonism decreased 32.0% per decade (relative risk = 0.68; 95% confidence interval: 0.49–0.94) and 68.6% over the 30 years of the study. The decrease was similar in men (65.2%) and women (69.4%); however, the trend was significant only in women. Conclusions The incidence of drug‐induced parkinsonism increased with older age and was higher in women at all ages. Typical antipsychotic drugs were the most common cause. The incidence of drug‐induced parkinsonism decreased over the 30 years of the study because of changes in drug use. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Objectives To identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an aging population and to estimate associations between frailty trajectories and emergency department visits, hospitalizations, and all‐cause mortality. Design Population‐based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota residents aged 60–89 in 2005. Measurements Longitudinal changes in frailty between 2005 and 2012 were measured by constructing a yearly Rockwood frailty index incorporating body mass index, 17 comorbidities, and 14 activities of daily living. The frailty index measures variation in health status as the proportion of deficits present of the 32 considered (range 0–1). Results Of the 16,443 Olmsted County residents aged 60–89 in 2005, 12,270 (74.6%) had at least 3 years of frailty index measures and were retained for analysis. The median baseline frailty index increased with age (0.11 for 60–69, 0.14 for 70–79, 0.19 for 80–89). Three distinct frailty trajectories were identified in individuals aged 60–69 at baseline and two trajectories in those aged 70–79 and 80–89. Within each decade of age, increasing frailty trajectories were associated with greater risks of emergency department visits, hospitalization, and all‐cause mortality, even after adjustment for baseline frailty index. Conclusion The number of frailty trajectories differed according to age. Within each age group, those in the highest frailty trajectory had greater healthcare use and worse survival. Frailty trajectories may offer a way to target aging individuals at high risk of hospitalization or death for therapeutic or preventive interventions.