Inferring DNA methylation in non-skeletal tissues of ancient specimens.

Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual.

Understanding Health Care Provider Burnout When Caring for Patients With Refractory Epilepsy in the United States.

Background And Objectives: Among health care providers (HCPs), neurologists have one of the highest rates of burnout in the United States, compromising the quality and accessibility of patient care. Patients with refractory epilepsy are especially challenging to treat. This study aims to understand the burnout level in neurologists treating patients with refractory epilepsy and identify key contributing factors.

R-Loop Accumulation in Spliceosome Mutant Leukemias Confers Sensitivity to PARP1 Inhibition by Triggering Transcription-Replication Conflicts.

Unlabelled: RNA splicing factor (SF) gene mutations are commonly observed in patients with myeloid malignancies. Here we showed that SRSF2- and U2AF1-mutant leukemias are preferentially sensitive to PARP inhibitors (PARPi), despite being proficient in homologous recombination repair. Instead, SF-mutant leukemias exhibited R-loop accumulation that elicited an R-loop-associated PARP1 response, rendering cells dependent on PARP1 activity for survival.

PRC2-independent actions of H3.3K27M in embryonic stem cell differentiation.

The histone H3 variant, H3.3, is localized at specific regions in the genome, especially promoters and active enhancers, and has been shown to play important roles in development. A lysine to methionine substitution in position 27 (H3.

Medical and nursing home costs: From cognitively unimpaired through dementia.

Introduction: Efforts to model the cost-effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing-home (NH) costs.

Methods: A stratified-random sample of Olmsted County, MN, residents ages 70-89 years (N = 3545), well-characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider-linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated.

Antisense oligonucleotide-based drug development for Cystic Fibrosis patients carrying the 3849+10 kb C-to-T splicing mutation.

Background: Antisense oligonucleotide (ASO)-based drugs for splicing modulation were recently approved for various genetic diseases with unmet need. Here we aimed to develop an ASO-based splicing modulation therapy for Cystic Fibrosis (CF) patients carrying the 3849+10 kb C-to-T splicing mutation in the CFTR gene.

Methods: We have screened, in FRT cells expressing the 3849+10 kb C-to-T splicing mutation, ~30 2'-O-Methyl-modified phosphorothioate ASOs, targeted to prevent the recognition and inclusion of a cryptic exon generated due to the mutation.

Objective Estimates of Direct-Medical Costs Among Persons Aged 3 to 38 Years With and Without Research-Defined Autism Spectrum Disorder Ascertained During Childhood: A Population-Based Birth-Cohort Study.

Objectives: Accurate estimates of autism spectrum disorder (ASD)-associated medical costs are essential for predicting future care needs, allocating resources, identifying best practices, and modeling cost-effectiveness. Most existing studies have either employed subjective cost data or ascertained ASD using self-reported or International Classification of Diseases-coded diagnoses. Such ascertainment is especially problematic for identifying milder ASD among older individuals never diagnosed with ASD.

Venous Thromboembolism (VTE) Incidence and VTE-Associated Survival among Olmsted County Residents of Local Nursing Homes.

Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources.

Nursing Home Use Across The Spectrum of Cognitive Decline: Merging Mayo Clinic Study of Aging With CMS MDS Assessments.

Background/objectives: Objective, complete estimates of nursing home (NH) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs.

Design: Retrospective longitudinal study.

Setting: Olmsted County, MN.

Skilled Nursing Facility Use and Hospitalizations in Heart Failure: A Community Linkage Study.

Objectives: To examine the effect of skilled nursing facility (SNF) use on hospitalizations in patients with heart failure (HF) and to examine predictors of hospitalization in patients with HF admitted to a SNF.

Patients And Methods: Olmsted County, Minnesota, residents with first-ever HF from January 1, 2000, through December 31, 2010, were identified, and clinical data were linked to SNF utilization data from the Centers for Medicare and Medicaid Services. Andersen-Gill models were used to determine the association between SNF use and hospitalizations and to determine predictors of hospitalization.

Risk factors for venous thromboembolism after acute trauma: A population-based case-cohort study.

Background: Predictors of venous thromboembolism (VTE) after trauma are uncertain.

Objective: To identify independent predictors of VTE after acute trauma.

Methods: Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE within 92days after hospitalization for acute trauma over the 18-year period, 1988-2005.

Direct Medical Costs Attributable to Cancer-Associated Venous Thromboembolism: A Population-Based Longitudinal Study.

Purpose: The purpose of this study is to estimate medical costs attributable to venous thromboembolism among patients with active cancer.

Methods: In a population-based cohort study, we used Rochester Epidemiology Project (REP) resources to identify all Olmsted County, Minn. residents with incident venous thromboembolism and active cancer over the 18-year period, 1988-2005 (n = 374).

Childhood Attention-Deficit/Hyperactivity Disorder, Sex, and Obesity: A Longitudinal Population-Based Study.

Objective: To assess obesity rates during childhood and young adulthood in patients with attention-deficit/hyperactivity disorder (ADHD) and age- and sex-matched controls derived from a population-based birth cohort because cross-sectional studies suggest an association between ADHD and obesity.

Patients And Methods: Study subjects included patients with childhood ADHD (n=336) and age- and sex-matched non-ADHD controls (n=665) from a 1976 to 1982 birth cohort (N=5718). Height, weight, and stimulant treatment measurements were abstracted retrospectively from medical records documenting care provided from January 1, 1976, through August 31, 2010.

Trends in Coronary Atherosclerosis: A Tale of Two Population Subgroups.

Background: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined.

Costs of venous thromboembolism associated with hospitalization for medical illness.

Objectives: To determine population-based estimates of medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for acute medical illness.

Study Design: Population-based cohort study conducted in Olmsted County, Minnesota.

Methods: Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County residents with objectively diagnosed incident VTE during or within 92 days of hospitalization for acute medical illness over the 18-year period of 1988 to 2005 (n=286).

Direct medical costs and source of cost differences across the spectrum of cognitive decline: a population-based study.

Background: Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild cognitive impairment (MCI), newly discovered dementia, and prevalent dementia.

Methods: Subjects were a subset of the Mayo Clinic Study of Aging stratified-random sampling of Olmsted County, MN, residents aged 70 to 89 years. A neurologist reviewed provider-linked medical records to identify prevalent dementia (review date = index).

Direct medical costs attributable to venous thromboembolism among persons hospitalized for major operation: a population-based longitudinal study.

Background: We estimated medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for major operation.

Methods: Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN, residents with objectively diagnosed incident VTE within 92 days of hospitalization for major operation during an 18-year period, 1988-2005 (n = 355). One Olmsted County resident hospitalized for major operation without VTE was matched to each case on event date (±1 year), type of operation, duration of previous medical history, and active cancer status.

Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

The purpose of this study was to offer detailed information about stimulant medication treatment provided throughout childhood to 379 children with research-identified attention-deficit hyperactivity disorder (ADHD) in the 1976-1982 Rochester, MN, birth cohort. Subjects were retrospectively followed from birth until a mean of 17.2 years of age.

Rethinking guidelines for VTE risk among nursing home residents: a population-based study merging medical record detail with standardized nursing home assessments.

Background: Nursing home (NH) residents are at increased risk for both VTE and bleeding from pharmacologic prophylaxis. Construction of prophylaxis guidelines is hampered by NH-specific limitations with VTE case identification and characterization of risk. We addressed these limitations by merging detailed provider-linked Rochester Epidemiology Project (REP) medical records with Centers for Medicare and Medicaid Services Minimum Data Set (MDS) NH assessments.

Familial risk of epilepsy: a population-based study.

Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County.

Billing code algorithms to identify cases of peripheral artery disease from administrative data.

Objective: To construct and validate billing code algorithms for identifying patients with peripheral arterial disease (PAD).

Methods: We extracted all encounters and line item details including PAD-related billing codes at Mayo Clinic Rochester, Minnesota, between July 1, 1997 and June 30, 2008; 22 712 patients evaluated in the vascular laboratory were divided into training and validation sets. Multiple logistic regression analysis was used to create an integer code score from the training dataset, and this was tested in the validation set.

Long-term survival after traumatic brain injury: a population-based analysis controlled for nonhead trauma.

Objective: To examine the contribution of co-occurring nonhead injuries to hazard of death after traumatic brain injury (TBI).

Participants: A random sample of Olmsted County, Minnesota, residents with confirmed TBI from 1987 through 1999 was identified.

Design: Each case was assigned an age- and sex-matched, non-TBI "regular control" from the population.

Asthma and proinflammatory conditions: a population-based retrospective matched cohort study.

Objective: To determine the association between asthma and proinflammatory conditions.

Participants And Methods: This 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.