Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry.

Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis.

Accuracy of a composite event definition for hypoglycemia.

Purpose: To evaluate the accuracy of a composite definition for the identification of hypoglycemia events that used both administrative claims and laboratory data in a cohort of patients.

Methods: We reviewed medical records in a sample of presumed hypoglycemia events among patients who received care at the Veterans Health Administration Tennessee Valley Healthcare System in 2001 to 2012. A hypoglycemia event was defined as a hospitalization or emergency department visit judged by the treating clinician to be due to hypoglycemia, or an outpatient laboratory or point-of-care blood glucose measurement <60 mg/dL.

Disentangling the genetics of lean mass.

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.

Interrelated Neuromuscular and Clinical Risk Factors That Contribute to Falls.

Background: Neuromuscular and clinical factors contribute to falls among older adults, yet the interrelated nature of these factors is not well understood. We investigated the relationships between these factors and how they contribute to falls, which may help optimize fall risk assessment and prevention.

Methods: A total of 365 primary care patients (age = 77 ± 7, 67% female) were included from the Boston Rehabilitative Impairment Study of the Elderly.

Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice.

Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span.

Effect on VA Patient Satisfaction of Provider's Use of an Integrated Viewer of Multiple Electronic Health Records.

Purpose: To examine associations between patient perceptions that their provider was knowledgeable of their medical history and clinicians' early adoption of an application that presents providers with an integrated longitudinal view of a patient's electronic health records (EHR) from multiple healthcare systems.

Method: This retrospective analysis utilizes provider audit logs from the Veterans Health Administration Joint Legacy Viewer (JLV) and patient responses to the Survey of Patient Healthcare Experiences Patient-Centered Medical Home (SHEP/PCMH) patient satisfaction survey (FY2016) to assess the relationship between the primary care provider being an early adopter of JLV and patient perception of the provider's knowledge of their medical history. Multivariate logistic regression models were used to control for patient age, race, sex education, health status, duration of patient-provider relationship, and provider characteristics.

Genome-wide association analysis of common genetic variants of resistant hypertension.

Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES).

Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice.

To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice.

Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD.

Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function. We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.

Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease.

Study Design: Retrospective observational study.

Association Between Hospice Length of Stay, Health Care Utilization, and Medicare Costs at the End of Life Among Patients Who Received Maintenance Hemodialysis.

Importance: Patients with end-stage renal disease are less likely to use hospice services than other patients with advanced chronic illness. Little is known about the timing of hospice referral in this population and its association with health care utilization and costs.

Objective: To examine the association between hospice length of stay and health care utilization and costs at the end of life among Medicare beneficiaries who had received maintenance hemodialysis.

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death.

Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs.

Importance: The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.

Objective: To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).

Palliative Care Disincentives in CKD: Changing Policy to Improve CKD Care.

The dominant health delivery model for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States, which focuses on provision of dialysis, is ill-equipped to address many of the needs of seriously ill patients. Although palliative care may address some of these gaps in care, its integration into advanced CKD care has been suboptimal due to several health system barriers. These barriers include uneven access to specialty palliative care services, underdeveloped models of care for seriously ill patients with advanced CKD, and misaligned policy incentives.

Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

A correction to this article has been published and is linked from the HTML version of this article.

Effect of controlled cortical impact on the passage of pituitary adenylate cyclase activating polypeptide (PACAP) across the blood-brain barrier.

Injuries to the central nervous system can affect the blood-brain barrier (BBB), including disruption and influencing peptide transport across the BBB. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neurotrophic and neuroprotective peptide currently being investigated for its therapeutic role following injury to the central nervous system and can cross the BBB in a saturable manner. The goal of the current study was to investigate for the first time PACAP38 uptake by the brain following traumatic brain injury (TBI).

An innovative educational clinical experience promoting geriatric exercise.

Formal educational training in physical activity promotion is relatively sparse throughout the medical education system. The authors describe an innovative clinical experience in physical activity directed at medical clinicians on a geriatrics rotation. The experience consists of a single 2 1/2 hour session, in which learners are partnered with geriatric patients engaged in a formal supervised exercise program.

Influence of metabolic syndrome and race on the relationship between intensive blood pressure control and cardiovascular outcomes in the SPRINT cohort.

Aims: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether the effects varied by race/ethnicity.

Methods: We performed post hoc analyses among non-Hispanic black, non-hispanic white and Hispanic participants, with and without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who were randomized to a systolic blood pressure (SBP) target of <120 mm Hg (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N = 4553). The median follow-up was 3.

Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD.

Background: Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m; however, evidence for benefits of nephrology care are mixed.

Study Design: Observational cohort using landmark analysis.

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10) or suggestively genome wide (p < 2.

Habitual sleep and kidney function in chronic kidney disease: the Chronic Renal Insufficiency Cohort study.

Physiological evidence suggests that sleep modulates kidney function. Our objective was to examine the cross-sectional association between kidney function and objectively-estimated habitual sleep duration, quality and timing in a cohort of patients with mild to moderate chronic kidney disease. This study involved two US clinical centers of the Chronic Renal Insufficiency Cohort (CRIC) study, including 432 participants in a CRIC ancillary sleep study.

Persistent Gaps in Use of Advance Directives Among Nursing Home Residents Receiving Maintenance Dialysis.

This data analysis seeks to determine whether changes in the use of advance directives between 2000 and 2010 are related to changing patterns of end-of-life care among nursing home residents receiving dialysis.