An Exploratory Study Using Electronic Medical Records to Assess the Feasibility of Establishing Cohorts of Patients with Genetic Causes of Parkinson's Disease.

Background: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson's disease (PD).

Objective: To explore the use of the electronic medical records (EMRs) to identify participants with PD.

Methods: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2) and beta-glucocerebrosidase (GBA) variants.

A Feasibility Study: Testing Whether a Sleep Application Providing Objective Sleep Data to Physicians Improves Patient-Physician Communication Regarding Sleep Experiences, Habits, and Behaviors.

Introduction: Sleep tracker data have not been utilized routinely in sleep-related disorders and their management. Sleep-related disorders are common in primary care practice and incorporating sleep tracker data may help in improving patient care. We conducted a pilot study to assess the feasibility of a sleep program using the Fitbit Charge 2™ device and SleepLife application.

Factors associated with clinical inertia in type 2 diabetes mellitus patients treated with metformin monotherapy.

To assess demographic and clinical characteristics associated with clinical inertia in a real-world cohort of type 2 diabetes mellitus patients not at hemoglobin A1c goal (<7%) on metformin monotherapy. Adult (≥18 years) type 2 diabetes mellitus patients who received care at Massachusetts General Hospital/Brigham and Women's Hospital and received a new metformin prescription between 1992 and 2010 were included in the analysis. Clinical inertia was defined as two consecutive hemoglobin A1c measures ≥7% ≥3 months apart while remaining on metformin monotherapy (i.

Development of an Algorithm to Identify Patients with Physician-Documented Insomnia.

We developed an insomnia classification algorithm by interrogating an electronic medical records (EMR) database of 314,292 patients. The patients received care at Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH), or both, between 1992 and 2010. Our algorithm combined structured variables (such as International Classification of Diseases 9th Revision [ICD-9] codes, prescriptions, laboratory observations) and unstructured variables (such as text mentions of sleep and psychiatric disorders in clinical narrative notes).

Relationship between tooth loss and peripheral arterial disease among women.

Aim: We assessed the longitudinal association between tooth loss and peripheral arterial disease (PAD) within the Nurses' Health Study.

Materials And Methods: After excluding participants with prior cardiovascular diseases, 277 of 79,663 women were confirmed as PAD cases during 16 years of follow-up. Number of teeth and recent tooth loss were reported initially in 1992.

Predictive Modeling of Physician-Patient Dynamics That Influence Sleep Medication Prescriptions and Clinical Decision-Making.

Insomnia remains under-diagnosed and poorly treated despite its high economic and social costs. Though previous work has examined how patient characteristics affect sleep medication prescriptions, the role of physician characteristics that influence this clinical decision remains unclear. We sought to understand patient and physician factors that influence sleep medication prescribing patterns by analyzing Electronic Medical Records (EMRs) including the narrative clinical notes as well as codified data.

The Effect of Limited Health Literacy on How Internet Users Learn About Diabetes.

The Internet continues to be an important supplemental health information resource for an increasing number of U.S. adults, especially for those with a new or existing chronic condition.

The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin of 6.5% or Greater Is Pronounced in the Haptoglobin 2-2 Genotype.

Background: Research targeting glycosylated hemoglobin A1c (HbA1c) to <6.5% to prevent coronary heart disease (CHD) events has conflicting results. We previously observed the haptoglobin (Hp) Hp2-2 genotype is associated with a ∼10-fold increased CHD risk among individuals with HbA1c ≥6.

Multilocus heterozygosity and coronary heart disease: nested case-control studies in men and women.

Background: Generalized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.

Methods: Using the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses' Health Study.

Low carbohydrate diet from plant or animal sources and mortality among myocardial infarction survivors.

Background: The healthiest dietary pattern for myocardial infarction (MI) survivors is not known. Specific long-term benefits of a low-carbohydrate diet (LCD) are unknown, whether from animal or vegetable sources. There is a need to examine the associations between post-MI adherence to an LCD and all-cause and cardiovascular mortality.

β2-microglobulin, cystatin C, and creatinine and risk of symptomatic peripheral artery disease.

Background: β2-Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, β2-microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD).

Methods And Results: We conducted nested case-control studies among women within the Nurses' Health Study (1990-2010) and among men within the Health Professionals Follow-up Study (1994-2008) with the use of archived blood samples collected before PAD diagnosis.

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.

Objective: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD.

Methods: We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010).

Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study.

Objective: To evaluate the associations of dietary fiber after myocardial infarction (MI) and changes in dietary fiber intake from before to after MI with all cause and cardiovascular mortality.

Design: Prospective cohort study.

Setting: Two large prospective cohort studies of US women and men with repeated dietary measurements: the Nurses' Health Study and the Health Professionals Follow-Up Study.

Effects of protein engineering and rational mutagenesis on crystal lattice of single chain antibody fragments.

Protein crystallization is dependent upon, and sensitive to, the intermolecular contacts that assist in ordering proteins into a three-dimensional lattice. Here we used protein engineering and mutagenesis to affect the crystallization of single chain antibody fragments (scFvs) that recognize the EE epitope (EYMPME) with high affinity. These hypercrystallizable scFvs are under development to assist difficult proteins, such as membrane proteins, in forming crystals, by acting as crystallization chaperones.

Better diet quality and decreased mortality among myocardial infarction survivors.

Importance: Information about diet after myocardial infarction (MI) and mortality is limited, despite the growing number of MI survivors in the United States.

Objective: To examine the association of post-MI dietary quality and changes from pre- to post-MI with all-cause and cardiovascular mortality among MI survivors.

Design, Setting, And Participants: We included 2258 women from the Nurses' Health Study and 1840 men from the Health Professionals Follow-up Study.

Oxidation-specific biomarkers and risk of peripheral artery disease.

Objectives: The goal of this study was to examine the prospective association between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on apolipoprotein B-100-containing lipoproteins (OxPL/apoB) and lipoprotein (a) [Lp(a)], and risk of peripheral artery disease (PAD). We examined, as secondary analyses, indirect measures of oxidized lipoproteins, including autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100 immune complexes (ApoB-IC).

Background: Biomarkers to predict the development of PAD are lacking.

Hemoglobin a1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women.

Background: Hemoglobin A1c (HbA1c), a time-integrated marker of glycemic control, predicts risk of coronary heart disease (CHD) among diabetics. Few studies have examined HbA1c and risk of CHD among women and men without clinically elevated levels or previously diagnosed diabetes.

Methods And Results: We conducted parallel nested case-control studies among women (Nurses' Health Study) and men (Health Professionals Follow-up Study).

Total adiponectin and risk of symptomatic lower extremity peripheral artery disease in men.

Objective: Lower concentrations of adiponectin have been linked to subsequent risk of coronary heart disease in healthy individuals. Whether similar relationships exist for the development of systemic atherosclerosis, such as peripheral artery disease (PAD), is uncertain. We investigated the association between total adiponectin and risk of lower extremity PAD.

Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin.

Objectives: This study sought to investigate into the biologically plausible interaction between the common haptoglobin (Hp) polymorphism rs#72294371 and glycosylated hemoglobin (HbA(1c)) on risk of coronary heart disease (CHD).

Background: Studies of the association between the Hp polymorphism and CHD report inconsistent results. Individuals with the Hp2-2 genotype produce Hp proteins with an impaired ability to prevent oxidative injury caused by elevated HbA(1c).

Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men.

Context: Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown.

Objective: To estimate the degree to which the 4 conventional cardiovascular risk factors of smoking, hypertension, hypercholesterolemia, and type 2 diabetes are associated with the risk of PAD among men.

Design, Setting, And Participants: Prospective study of 44,985 men in the United States without a history of cardiovascular disease at baseline in 1986; participants in the Health Professionals Follow-up Study were followed up for 25 years until January 2011.

Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study.

Aims: The aim of this study was to examine the association between long-term alcohol consumption, alcohol consumption before and after myocardial infarction (MI), and all-cause and cardiovascular mortality among survivors of MI.

Methods And Results: The Health Professionals Follow-up Study (HPFS) is a prospective cohort study of 51 529 US male health professionals. From 1986 to 2006, 1818 men were confirmed with incident non-fatal MI.

Crystallization chaperone strategies for membrane proteins.

From G protein-coupled receptors to ion channels, membrane proteins represent over half of known drug targets. Yet, structure-based drug discovery is hampered by the dearth of available three-dimensional models for this large category of proteins. Other than efforts to improve membrane protein expression and stability, current strategies to improve the ability of membrane proteins to crystallize involve examining many orthologs and DNA constructs, testing the effects of different detergents for purification and crystallization, creating a lipidic environment during crystallization, and cocrystallizing with covalent or non-covalent soluble protein chaperones with an intrinsic high propensity to crystallize.

Conversion of scFv peptide-binding specificity for crystal chaperone development.

In spite of advances in protein expression and purification over the last decade, many proteins remain recalcitrant to structure determination by X-ray crystallography. One emerging tactic to obtain high-quality protein crystals for structure determination, particularly in the case of membrane proteins, involves co-crystallization with a protein-specific antibody fragment. Here, we report the development of new recombinant single-chain antibody fragments (scFv) capable of binding a specific epitope that can be introduced into internal loops of client proteins.

CRP gene variation and risk of community-acquired pneumonia.

Background And Objective: CRP has several potentially antibacterial effects, and variation in the CRP gene is known to influence CRP levels. Whether this variation influences risk of infection, and hence whether CRP has anti-infective activity in humans, is uncertain.

Methods: We evaluated a series of haplotype-tagging single nucleotide polymorphisms among 5374 individuals in the Cardiovascular Health Study, a cohort of older adults from four communities, who were followed for community-acquired pneumonia for 12-13 years.