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Health care resource consumption is a growing concern. The aim of this study was to examine the associations between diet quality and body mass index with health care resource use (HRU) in a cohort of advanced age. Participants in the Geisinger Rural Aging Study (n=5,993) were mailed demographic and dietary questionnaires in 2009. Of those eligible, 2,995 (50%; 1,267 male, 1,728 female; mean age 81.4±4.4 years) provided completed surveys. Multivariate negative binomial models were used to estimate relative risk and 95% CI of HRU outcomes with diet quality as assessed by the Dietary Screening Tool score and body mass index determined from self-reported height and weight. Poor diet quality was associated with a 20% increased risk for emergency room (ER) visits. Fruit and vegetable consumption was grouped into quintiles of intake, with the highest quintile serving as the reference group in analyses. The three lowest fruit and vegetable quintiles were associated with increased risk for ER visits (23% to 31%); the lowest quintile increased risk for inpatient visits (27%). Obesity increased risk of outpatient visits; however, individuals with class I obesity were less likely than normal-weight individuals to have ER visits (relative risk=0.84; 95% CI 0.70 to 0.99). Diets of greater quality, particularly with greater fruit and vegetable intake, are associated with favorable effects on HRU outcomes among older adults. Overweight and obesity are associated with increased outpatient HRU and, among obese individuals, with decreased ER visits. These findings suggest that BMI and diet quality beyond age 74 years continue to affect HRU measures.

Objective To evaluate the impact of adult bariatric surgery on the body mass index (BMI) of children living in the same household. Methods A retrospective case-control study. Case dyads (n = 128) were composed of one adult who had bariatric surgery and one child at the same address. Control dyads (n = 384) were composed of an adult with obesity but no bariatric surgery and a child at the same address. Two-sample t-test was used to determine whether the differences between actual and expected BMI at follow-up (post-surgery) differed between children in the case and control dyads. Results Among boys who were overweight, boys who lived with a surgery patient had a lower than expected BMI post-surgery, while boys who did not live with a surgery patient had a higher than expected BMI at follow-up (P = 0.045). Differences between actual and expected BMIs of children were not significantly different between cases and controls in girls or in children in other weight classes. Conclusions Overweight boys who lived with an adult bariatric surgery patient had a lower than expected BMI after surgery as compared to controls. Future studies may be warranted to determine the mechanisms by which these children experience collateral weight loss.

OBJECTIVE Gastric bypass surgery is an effective therapy for extreme obesity. However, substantial variability in weight loss outcomes exists that remains largely unexplained. Our objective was to determine whether any commonly collected pre-operative clinical variables were associated with weight loss following Roux-en-Y gastric bypass surgery. DESIGN The analysis was based on a prospectively recruited observational cohort of 2365 patients who underwent Roux-en-Y gastric bypass surgery from 2004-2009. Weight loss was stratified into three major phases, early (0-6 months), nadir, and long-term (>36 months). Multivariate regression models were constructed using a database of over 350 variables. RESULTS A total of 12-14 pre-operative variables were independently associated (p50 years, and the presence of fibrosis on liver biopsy. CONCLUSIONS Several variables previously associated with poorer weight loss after RYGB surgery including age, baseline BMI, and type 2 diabetes were replicated. Several others suggest possible clinical interventions for post-operative management of RYGB patients to improve weight loss outcomes.

Summary Background About 60% of patients with type 2 diabetes achieve remission after Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to preoperatively predict the probability of remission. Our goal was to develop a way to predict probability of diabetes remission after RYGB surgery on the basis of preoperative clinical criteria. Methods In a retrospective cohort study, we identified individuals with type 2 diabetes for whom electronic medical records were available from a primary cohort of 2300 patients who underwent RYGB surgery at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb 15, 2011. Partial and complete remission were defined according to the American Diabetes Association criteria. We examined 259 clinical variables for our algorithm and used multiple logistic regression models to identify independent predictors of early remission (beginning within first 2 months after surgery and lasting at least 12 months) or late remission (beginning more than 2 months after surgery and lasting at least 12 months). We assessed a final Cox regression model with a consistent subset of variables that predicted remission, and used the resulting hazard ratios (HRs) to guide creation of a weighting system to produce a score (DiaRem) to predict probability of diabetes remission within 5 years. We assessed the validity of the DiaRem score with data from two additional cohorts. Findings Electronic medical records were available for 690 patients in the primary cohort, of whom 463 (63%) had achieved partial or complete remission. Four preoperative clinical variables were included in the final Cox regression model: insulin use, age, HbA 1c concentration, and type of antidiabetic drugs. We developed a DiaRem score that ranges from 0 to 22, with the greatest weight given to insulin use before surgery (adding ten to the score; HR 5·90, 95% CI 4·41–7·90; p Interpretation The DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery. Funding Geisinger Health System and the US National Institutes of Health.

Objectives. The accumulation of lipids stored as excess triglycerides in the liver (steatosis) is highly prevalent in obesity and has been associated with several clinical characteristics, but most studies have been based on relatively small sample sizes using a limited set of variables. We sought to identify clinical factors associated with liver fat accumulation in a large cohort of patients with extreme obesity.Methods. We analyzed 2929 patients undergoing intraoperative liver biopsy during a primary bariatric surgery. Univariate and multivariate regression modeling was used to identify associations with over 200 clinical variables with the presence of any fat in the liver and with moderate to severe versus mild fat accumulation.Results. A total of 19 data elements were associated with the presence of liver fat and 11 with severity of liver fat including ALT and AST, plasma lipid, glucose, and iron metabolism variables, several medications and laboratory measures, and sleep apnea. The accuracy of a multiple logistic regression model for presence of liver fat was 81% and for severity of liver fat accumulation was 77%.Conclusions. A limited set of clinical factors can be used to model hepatic fat accumulation with moderate accuracy and may provide potential mechanistic insights in the setting of extreme obesity.

We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery.Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers.Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed.The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P0.0001), increasing age (P0.005), male gender (P0.001), pulmonary hypertension (P0.0001), congestive heart failure (P=0.0008), and liver disease (P=0.038). When the RYGB risk score was applied, a significant trend (P0.0001) between increasing risk score and mortality rate is found.Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.

In an aging population, potentially modifiable factors impacting mortality such as diet quality, body mass index (BMI), and health-related quality of life (HRQOL) are of interest. Surviving members of the Geisinger Rural Aging Study (GRAS) (n = 5,993; aged ?74 years) were contacted in the fall of 2009. Participants in the present study were the 2,995 (1,267 male, 1,728 female; mean age 81.4 ± 4.4 years) who completed dietary and demographic questionnaires and were enrolled in the Geisinger Health Plan over follow-up (mean = 3.1 years). Cox proportional hazards multivariate regression models were used to examine the associations between all-cause mortality and BMI, diet quality, and HRQOL. Compared to GRAS participants with BMIs in the normal range, a BMI < 18.5 was associated with increased mortality (HR 1.85 95%CI 1.09, 3.14, P = 0.02), while a BMI of 25-29.9 was associated with decreased risk of mortality (HR 0.71 95%CI 0.55, 0.91, P =0.007). Poor diet quality increased risk for mortality (HR 1.53 95%CI 1.06, 2.22, P = 0.02). Finally, favorable health-related quality of life was inversely associated with mortality (HR 0.09 95%CI 0.06, 0.13, P < 0.0001). Higher diet quality and HALex scores, and overweight status, were associated with reduced all-cause mortality in a cohort of advanced age. While underweight (BMI < 18.5) increased risk of all-cause mortality, no association was found between obesity and all-cause mortality in this aged cohort.

Previously, we reported that hepatic muscarinic receptors modulate both acute and chronic liver injury, however, the role of muscarinic receptors in fatty liver disease is unclear. We observed in patients who underwent weight loss surgery, a decrease in hepatic expression of M3 muscarinic receptors (M3R). We also observed that fat loading of hepatocytes, increased M3R expression. Based on these observations, we tested the hypothesis that M3R regulate hepatocyte lipid accumulation. Incubation of AML12 hepatocytes with 1 mM oleic acid resulted in lipid accumulation that was significantly reduced by co-treatment with a muscarinic agonist (pilocarpine or carbachol), an effect blocked by atropine (a muscarinic antagonist). Similar treatment of Hepa 1–6 cells, a mouse hepatoblastoma cell line, showed comparable results. In both, control and fat-loaded AML12 cells, pilocarpine induced time-dependent AMPKα phosphorylation and significantly up-regulated lipolytic genes (ACOX1, CPT1, and PPARα). Compound C, a selective and reversible AMPK inhibitor, significantly blunted pilocarpine-mediated reduction of lipid accumulation and pilocarpine-mediated up-regulation of lipolytic genes. BAPTA-AM, a calcium chelator, and STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, attenuated agonist-induced AMPKα phosphorylation. Finally, M3R siRNA attenuated agonist-induced AMPKα phosphorylation as well as agonist-mediated reduction of hepatocyte steatosis. In conclusion, this proof-of-concept study demonstrates that M3R has protective effects against hepatocyte lipid accumulation by activating AMPK pathway and is a potential therapeutic target for non-alcoholic fatty liver disease.

Bariatric surgery may increase the risk of substance use. The purpose of this study was to prospectively assess smoking and alcohol use before and after bariatric surgery, identify characteristics associated with alcohol use and smoking, and examine substance use and weight loss. Participants (N = 155, mean = 50.1 ± 11.3 y and 45.7 ± 7.0 kg/m(2)) were Roux-en-Y gastric bypass (RYGB) patients that completed surveys on substance use preoperatively and postoperatively. Alcohol use decreased significantly from the preoperative (72.3%) to the postoperative (63.2%) period. As preoperative alcohol quantity rose, the odds of consuming any alcohol postoperatively increased six-fold. Higher BMI increased the odds of high alcohol consumption. Older age decreased the odds of alcohol use and smoking. Smoking status did not differ pre- (19.4%) to post- (14.8%) surgery. Alcohol use and smoking were not associated with weight loss. After weight-loss surgery, alcohol use declined but smoking rates did not significantly change. Younger patients were more likely to use alcohol and smoke postoperatively. Patients with a higher BMI or a history of substance use may be more likely to use alcohol postoperatively.

OBJECTIVE Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. RESEARCH DESIGN AND METHODS Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. RESULTS Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. CONCLUSIONS Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.

Context: Roux-en-Y gastric bypass (RYGB) is among the most effective treatments for extreme obesity and obesity-related complications. However, despite its potential efficacy, many patients do not achieve and/or maintain sufficient weight loss. Objective: Our objective was to identify genetic factors underlying the variability in weight loss outcomes after RYGB surgery. Design: We conducted a genome-wide association study using a 2-stage phenotypic extreme study design. Setting: Patients were recruited from a comprehensive weight loss program at an integrated health system. Patients: Eighty-six obese (body mass index >35 kg/m2) patients who had the least percent excess body weight loss (%EBWL) and 89 patients who had the most %EBWL at 2 years after surgery were genotyped using Affymetrix version 6.0 single-nucleotide polymorphism (SNP) arrays. A second group from the same cohort consisting of 164 patients in the lower quartile of %EBWL and 169 from the upper quartile were selected for evaluation of candidate regions using custom SNP arrays. Intervention: We performed RYGB surgery. Main Outcome Measures: We assessed %EBWL at 2 years after RYGB and SNPs. Results: We identified 111 SNPs in the first-stage analysis whose frequencies were significantly different between 2 phenotypic extremes of weight loss (allelic χ2 test P < .0001). Linear regression of %EBWL at 2 years after surgery revealed 17 SNPs that approach P < .05 in the validation stage and cluster in or near several genes with potential biological relevance including PKHD1, HTR1A, NMBR, and IGF1R. Conclusions: This is the first genome-wide association study of weight loss response to RYGB. Variation in weight loss outcomes after RYGB may be influenced by several common genetic variants.

The prevalence of obesity-related adverse health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes.This study examined the association between dietary patterns and mortality and prevalence of obesity-related health outcomes, namely cardiovascular disease (CVD), type 2 diabetes mellitus, hypertension, and metabolic syndrome (MetSyn), over a 5-year follow-up period in adults aged 75 years or greater.A longitudinal observational study with cross-sectional dietary assessment.Rural Central Pennsylvania.Community-dwelling older adults (N = 449; 76.5 years old; 57% female).Multiple, unannounced, 24-hour dietary recalls were used to collect dietary intake. Cluster analysis was used to derive dietary patterns. Prevalence of CVD, diabetes mellitus, hypertension, and MetSyn was extracted from outpatient electronic medical records. Logistic regression was used to examine the associations between dietary patterns and health outcomes and mortality.'Sweets and Dairy', 'Health-Conscious' and 'Western' dietary patterns were identified. Compared to the 'Health-Conscious' pattern, those in the 'Sweets and Dairy' pattern had increased odds of hypertension over the follow-up period; adjusted odds ratio (95% CI) was 2.18 (1.11-4.30). No significant associations were found for CVD, diabetes mellitus, MetSyn or mortality with dietary patterns.These findings support the potential value of healthy dietary patterns in the management of hypertension in older adults. We did not observe any other strong associations between dietary patterns and health outcomes or mortality in persons ≥ 75 years of age; thus failing to support the use of overly restrictive diet prescriptions for older persons, especially where food intake may be inadequate.

Open source is actually more secure and reliable than the alternatives. This is a conclusion based on the experience of creating a hosting/cloud Infrastructure as a Service (IaaS) company using entirely open source software and an ‘automate everything’ philosophy.

Objectives: Genome-wide association studies (GWAS) have led to the identification of single nucleotide polymorphisms in or near several loci that are associated with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We hypothesized that missense variants in GWAS and related candidate genes may underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme manifestation of NAFLD. Methods: We performed whole-exome sequencing on 6 Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4 obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis. Results: Sequence analysis was performed on 24 replicated GWAS and selected candidate obesity genes and 5 loci associated with NAFLD. No missense variants were identified in 19 of the 29 genes analyzed, although all patients carried at least 2 missense variants in the remaining genes without excess homozygosity. One patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was homozygous for benign and damaging MC3R variants. In addition, 1 patient with NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in PNPLA3. Conclusions: These results indicate that analyzing candidate loci previously identified by GWAS analyses using whole-exome sequencing is an effective strategy to identify potentially causative missense variants underlying extreme obesity and NAFLD-related cirrhosis.

Nutrient tranters (NT) facilitate nutrient absorption and contribute to the regulation of circulating nutrients. In this cross-sectional study, we determined the associations between the level of obesity; mRNA abundance for NTs; and serum concentrations of amino acids, short-chain fatty acids, and glucose in patients with morbid obesity undergoing a Roux-en-Y gastric bypass. Proximal jejunal samples were obtained at the time of surgery from 42 patients (90% female, age = 42.6 ± 11.9 years, pre-operative body mass index (BMI) = 55.5 ± 11.3 kg/m2) undergoing a Roux-en-Y gastric bypass. RNA was extracted from the jejunal mucosa and quantitative real-time–PCR was performed for the NTs studied. BMI negatively correlated with jejunal mRNA abundance of the amino acid NTs TauT (r = −0.625, p < 0.0001), ASCT2 (r = −0.320, p = 0.039), LAT1 (r = −0.304, p = 0.05). BMI positively correlated with jejunal mRNA abundance of the lactate/short-chain fatty acid NT SMCT1 (r = 0.543, p = 0.0002). Serum concentrations of the short-chain fatty acids, butyric, valeric, and isocaproic acid correlated positively with BMI (n = 30) (r = 0.45, r = 0.44, r = 0.36, p ≤ 0.05; respectively). Lower jejunal mRNA abundance for the amino acid NTs TauT, ASCT2, and LAT1 could protect against further obesity-related elevations in circulating amino acids. The positive correlation between BMI and the jejunal mRNA abundance of the high-affinity short-chain fatty acid/monocarboxylate transporter SMCT1 is intriguing and requires further investigation.

The explanation for reduced mortality among older persons with overweight or class I obesity compared to those of desirable weight remains unclear. Our objective was to investigate the joint effects of body mass index (BMI) and metabolic health status on all-cause mortality in a cohort of advanced age. Adults aged 74 ± 4.7 (mean ± SD) years at baseline (n = 4551) were categorized according to BMI (18.5-24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2)) and the presence or absence of a metabolically healthy phenotype (i.e., 0 or 1 risk factors based on a modified Adult Treatment Panel III). Metabolically unhealthy was ≥2 risk factors. There were 2294 deaths over a mean 10.9 years of follow up. Relative to metabolically healthy desirable weight, metabolically healthy overweight or class I obesity was not associated with a greater mortality risk (HR 0.90; 95 CI% 0.73-1.13 and HR 0.58; 95 CI% 0.42-0.80, respectively) (P-interaction0.001). Results remained consistent in rigorous sensitivity analyses. The "obesity paradox" may be partially explained by the inclusion of metabolically healthy overweight and obese older persons, who do not have elevated mortality risk, in population studies of BMI and mortality.

This study evaluated the social environment of bariatric surgery patients in the preoperative period. Forty bariatric surgery patients (mean = 46.2 ± 11.2 years), 35 adult cohabitating family members (mean = 45.2 ± 12.7 years), and 15 cohabitating children (mean = 11.5 ± 3.6 years) were recruited from a large rural medical center. Adult participants (patients and family members) completed height, weight, body composition, blood draws, and physical activity assessments (accelerometry), as well as eating behavior and social support inventories before the patient underwent bariatric surgery. Child participants completed demographic, height, and weight assessment only. Over 90 % of adult family members were overweight or obese (body mass index (BMI) ≥ 25 kg/m2, as were 50 % of children (BMI percentile ≥ 85 %). More than one third (37.1 %) of family members met the criteria for moderate to severe insulin resistance. Physical activity measured by accelerometry was moderately correlated between the patient and adult family members (r = 0.46, p = 0.023). Bariatric surgery patients reported high levels of social support from their family members on multiple social support measures. Many family members of bariatric surgery patients also lived with obesity and related comorbidities, and demonstrate high sedentary behavior. However, patients reported high levels of support from family members, including support in following a healthy diet and engaging in physical activity. Engaging families in behavior change may help bariatric surgery patients and their families to become healthier.

There is great anticipation for the predicted impact that the Precision Medicine Initiative will have on health outcomes.1 However, we do not need to wait to sequence the DNA of the proposed 1 million–person cohort for this initiative; we can make significant strides in improving the precision of care delivery now. There are sufficient data in existing electronic health record systems that can be used to facilitate tailored treatment decisions. For example, the DiaRem score, a validated score generated from data readily available in the medical record, can be used for patients with type 2 diabetes to predict whether bariatric surgery will lead to short-term remission of diabetes.2–4 Herein, we examine whether this score can be used to predict patients for whom bariatric surgery will result in cure of type 2 diabetes.5

Objective To examine the association between baseline body mass index (BMI, kg/m2) and all-cause mortality in a well-characterized cohort of older persons. Methods The association between BMI (both as a categorical and continuous variable) and all-cause mortality was investigated using 4,565 Geisinger Rural Aging Study participants with baseline age 74.0 ± 4.7 years (mean ± SD) and BMI 29.5 ± 5.3 kg/m2 over a mean of 10.9 ± 3.8 years of follow-up. Results The relationship between BMI (as a continuous variable) and all-cause mortality was found to be U-shaped (P nonlinearity

Objectives To determine sex bias in the selection of strategies to evaluate patients with acute myocardial infarction (AMI), and determine if the choice of strategy influences survival. Background Controversy exists regarding the role of female sex in the use of invasive evaluation for AMI and its possible effect on adverse outcomes. Methods Electronic health record data from the Geisinger Acute Myocardial Infarction Cohort (GAMIC) was analyzed which included 1,968 men and 1,047 women admitted to the Geisinger Medical Center between January 2001 and December 2006 with acute myocardial infarction (AMI).Multivariate logistic regression analyses were used to determine independent correlates of an invasive evaluation. Multivariate logistic regression modeling stratified on sex was used to determine when invasive evaluation was done and whether there was a correlation with mortality. Results In unadjusted analyses, male sex was a significant predictor for the use of invasive evaluation (odds ratio = 1.71, 95% CI = [1.46, 2.00]). Adjusted for baseline differences (like age, renal function, co-morbid conditions) multivariate analyses found no significant relationship between male sex and invasive evaluation (OR = 1.02, 95% CI = [0.82, 1.23]). Females in the STEMI group were found to be less revascularized. No difference was observed in the one-year mortality between women and men regardless of invasive evaluation or revascularization. Conclusions Sex was not independently associated with the occurrence of an invasive evaluation of a MI. Females in the STEMI group were less revascularized. There was no strong gender effect on survival irrespective of the performance on an invasive evaluation or revascularization. (J Interven Cardiol 2013;26:14–21)

J Clin Hypertens (Greenwich). 2012; 14:407–414. ©2012 Wiley Periodicals, Inc. Important questions concerning the comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) remain unanswered, including whether they are equally effective in reducing clinical end points and in which populations. An incident cohort of adult patients 18 years and older prescribed an ACE inhibitor or ARB between 2001 and 2008 was identified from Geisinger Clinic, a large community-based set of medical practices that uses a common electronic health record. Propensity score matching was used to balance the groups on baseline factors. The authors examined differences in mortality and new-onset coronary disease, chronic kidney disease, stroke, and diabetes for different patient subgroups based on sex and age. A total of 25,035 hypertensive patients newly prescribed an ACE inhibitor or ARB were identified. No differences were found in risk of death, coronary disease, chronic kidney disease, or stroke between those prescribed ACE inhibitors and those prescribed ARBs. Patients prescribed ARBs had a greater rate of new-onset diabetes (hazard ratio [HR], 1.28; confidence interval [CI], 1.08–1.52), and this was especially true for women (HR, 1.93; CI, 1.22–3.07). Within a large medical-practice based population, there was no evidence of differential effectiveness between ACE inhibitors and ARBs for most outcomes, with diabetes being the notable exception.

Genome-wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg/m(2)) who underwent a preoperative diet/behavioral weight loss intervention and Roux-en-Y gastric bypass surgery were genotyped for single-nucleotide polymorphisms (SNPs) in or near the fat mass and obesity-associated (FTO), insulin induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), and proprotein convertase subtilisin/kexin type 1 (PCSK1) obesity genes. Association analysis was performed using recessive and additive models with pre- and postoperative weight loss data. An increasing number of obesity SNP alleles or homozygous SNP genotypes was associated with increased BMI (P < 0.0006) and excess body weight (P < 0.0004). No association between the amounts of weight lost from a short-term dietary intervention and any individual obesity SNP or cumulative number of obesity SNP alleles or homozygous SNP genotypes was observed. Linear mixed regression analysis revealed significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity SNP alleles or numbers of homozygous SNP genotypes (P < 0.0001). Initial BMI interacted with genotype to influence weight loss with initial BMI

Since 2001, Geisinger Health System densitometrists have interpreted dual-energy X-ray absorptiometries (DXAs) in a guideline-driven, consultative fashion. We believe that this approach results in more patients receiving appropriate treatment. Recently, one of our DXA centers chose to stop consultative reporting, providing us an opportunity to review the care rendered with 2 different styles of DXA reporting formats: Consultative vs Results Only. In this retrospective chart review, 100 consecutive DXAs with Consultative reporting and 100 consecutive DXAs with Results Only reporting were identified. The electronic health record was reviewed for a 3-mo interval after DXA result to identify whether a prescription medication was prescribed per system guidelines. Logistic regression compared the proportion of patients receiving a prescription treatment between the 2 groups. The Consultative report group received more prescription treatment compared with Results Only format (72% vs 50%) after controlling for patients' age and gender, odds ratio=2.64, 95% confidence interval=1.45–4.79 ( p =0.0014). Our study demonstrates that Consultative DXA reporting results in better care. Importantly, Consultative reporting takes additional time; yet, reimbursement for these efforts and expertise has been dramatically reduced. To appropriately reward the value of DXA testing and interpretation, Consultative reporting should be reimbursed at the previous higher reimbursement rate.

People who hunt deer from elevated tree stands may improve the chances of a successful hunt but also risk serious injury from a fall to the ground.The objective of the current investigation is to estimate the rates of injuries from falls from tree stands using a population-based study design.Annual and age-specific rates were calculated using injury data collected from 1987 to 2006 from all accredited Pennsylvania trauma centers and hunting license sales and game-take mail surveys from the Pennsylvania Game Commission.From 1987 through 2006, 2.73 people (n=499) per 100,000 licensed deer hunters were injured from falls from tree stands; seven people died. Rates increased from 0.59 in 1987 to 7.08 in 2006 (p0.001). Rates increased with age (p0.001) and were highest among hunters aged 40-49 years. The case-fatality rate was 1.4%.Falls from tree stands associated with deer hunting are an increasing and important cause of injuries, especially for older hunters. Surveillance for tree stand-related injuries should be enhanced and preventive initiatives developed and tested.

Purpose: Roux-en-Y gastric bypass surgery has become an increasingly common form of weight management. Early retrospective reviews have suggested that new onset nephrolithiasis develops in some patients after undergoing Roux-en-Y gastric bypass. We present a prospective longitudinal study to assess risk factors for nephrolithiasis after Roux-en-Y gastric bypass.Materials and Methods: A total of 45 morbidly obese patients scheduled to undergo Roux-en-Y gastric bypass surgery were enrolled in this prospective study between November 2006 and November 2007. Exclusion criteria included history of nephrolithiasis or inflammatory bowel disease. Serum uric acid, parathyroid hormone, calcium, albumin, and creatinine and 24-hour urine collections were obtained within 6 months before Roux-en-Y gastric bypass, and at 6 to 12 months postoperatively. A Wilcoxon signed-rank test was used to compare preoperative and postoperative serum laboratory values and 24-hour urine values. McNemar's test was used to determine if th...

The need for evidence-based teaching has become an important ideology for nurse educators who are frequently encouraged to expand their teaching strategies based on recent advances in technology and student learning styles. Traditional lecture is often preferred by students, yet the literature encourages case study methodology for the development of critical thinking. A pilot study was conducted comparing learning outcomes using two different teaching strategies: lecture and case study instruction. Recommendations for using case study as a teaching methodology are offered.

Objective To measure how rheumatologists across our health system performed with the American College of Rheumatology (ACR) quality indicators (QIs) for rheumatoid arthritis (RA) and methotrexate (MTX) drug safety, and to develop opportunities for improvement. Methods An electronic health record (EHR) review of 1,062 unique RA patients seen by 15 rheumatologists in a 1-year period was performed. Percentage of each QI met, reasons why the metric was not met, and performance of rheumatologists based on years of experience were evaluated. Results The percentage met was high for QI-2 (RA disease-modifying antirheumatic drug use; 94%), QI-3 (intervention if RA worse; 85%), and QI-4 (MTX risks discussion; 87%). Percentage met was lower for QI-1 (RA core data set; 69%), QI-5 (MTX baseline studies; 41%), and QI-6 (MTX followup studies; 46%). QI-1 and QI-5 were low due to most physicians missing a single test, and QI-6 was low because of few physicians driving the percentage down. Better QI performance was seen in rheumatologists with ≤10 years versus >10 years of experience for QI-1 (90% versus 64%; odds ratio [OR] 4.21, P = 0.004) and QI-3 (96% versus 82%; OR 4.47, P = 0.019). EHR chart review for this population required 179.3 hours. Conclusion Measurement allows us to better understand the quality of care that we deliver. In this systematic benchmarking of the ACR QIs in a large RA cohort, performance was excellent in RA treatment–related QIs. Significant variability was noted in RA and MTX monitoring measures, which can be addressed using process redesign techniques.

Objective: To estimate work impact of headache among migraineurs. Methods: Data were from a U.S. nationwide mailed questionnaire of 193,477 participants in the American Migraine Prevalence and Prevention study. Lost Productive Time (LPT) was the sum of missed hours plus reduced productivity hour equivalents. The cause of LPT was self-reported. Results: The mean LPT per week was 1.8 hours for headache and 2.8 for all health related causes; 76.5% of the headache-related LPT was explained by reduced performance (ie, presenteeism). The 29% of migraine cases with 11 headaches-d/mo accounted for 49% of overall LPT; the 19% of those with pain score of 9 to 10 o na0t o 10scale accounted for 33% of the overall LPT. Conclusions: Individuals with frequent and severe headaches account for a disproportionate share of the headache-related LPT. (J Occup Environ Med. 2008;50:736–745)

BACKGROUND The career choices of Mohs fellows have important implications for ensuring the quality of dermatologic surgery training during residency. No published data examine the career choices of fellows in Mohs micrographic surgery. OBJECTIVE To determine the number of Mohs fellows entering academics and to examine the influence of fellowship characteristics, scholarly activities, and personal background on career decision. METHODS A voluntary survey was distributed by mail in June 2004 to all Mohs fellows-in-training during 2003–2004. RESULTS Twenty-nine percent (12 of 42) of the fellows chose jobs in an academic or university setting. The practice setting of the fellowship, personal factors, and scholarly activities prior to fellowship did not correlate with career decision. By contrast, increased scholarly activities during fellowship and an interest in teaching did correlate with the choice to enter academics. CONCLUSIONS A significant percentage of Mohs fellows pursued academics. Increased academic productivity during the fellowship and an interest in teaching correlated with the decision to pursue an academic career. Fellowship directors interested in encouraging academic careers may find these data useful to structure their curricula and to mentor fellows inquiring about academic careers.

Type 2 diabetes is one of the nation's most prevalent chronic diseases. Although well-known practice guidelines exist, real-life clinical performance often falls short of benchmarks.Employ an electronic registry derived from a fully integrated electronic health record (EHR) as the cornerstone of an intervention to improve compliance with recommended diabetes performance measures in an integrated practice network.Geisinger Health System's network of 38 practice sites providing care to over 20,000 persons with diabetes located in a 40-county region of central and northeastern Pennsylvania.A multidisciplinary group of physicians worked to create a "bundle" of best practice measures for diabetes. This measurement tool was then used as part of a multifaceted intervention to improve physician performance in diabetes care, including audit and feedback, computerized reminders, and financial incentives. Changes in performance of individual measures and the total "bundle" were tracked monthly over 1 year.Significant increases were seen in all measures of diabetes care over the 12-month period of the study. Vaccination for pneumococcal disease and influenza improved from 56.5% to 80.8% (p.0001) and 55.1% to 71.0% (p.0001), respectively. The percentage of patients with ideal glucose control (HBA1c7.0) increased from 32.2% to 34.8% (p.001), and blood pressure control (130/80) improved from 39.7% to 43.9% (p.0001). The overall number of patients receiving all 9 "bundled" measurements improved from 2.4% to 6.5% (p.0001).Diabetes care improved significantly in response to a multifaceted intervention featuring the use of an EHR-derived registry in an integrated delivery system. More work is needed to demonstrate that such improvements will translate into improved patient health outcomes.

To understand variation in prevalence of urinary incontinence (UI) and risk factors, given different definitions.The National Health and Nutrition Examination Survey 2001-2002 data on UI were used. Prevalence, severity, and associated risk factors of stress, urge, mixed, and any UI were estimated in 2,875 adult women. Severe UI was defined as incontinence a few times or more per week. Moderate UI was defined as an incontinence frequency of a few times per month only, and mild UI was defined as incontinence frequency of a few times per year only. Odds ratios for the association of potential risk factors were examined in a logistic regression model.The overall prevalence of stress, urge, mixed, and any UI was 23.7%, 9.9%, 14.5%, and 49.2%, respectively. Prevalence of stress UI peaked at the fifth decade. Prevalence of urge and mixed UI increased with age. The largest number of risk factors and the strongest associations were found with severe UI. Age, ethnic background, and weight were significant risk factors common to all UI severity levels. Although parity and hysterectomy were risk factors for moderate and severe UI, they were not for mild UI.Prevalence of UI varies substantially by type and case definition. The stronger associations of known risk factors with severe UI and the lack of risk factors with lesser UI severity types suggest that severe UI includes primarily clinically significant cases, whereas mild UI represents transient or nonpathologic states that may not be clinically significant.III.

Genomic medicine research requires substantial time and resources to obtain phenotype data. The electronic health record offers potential efficiencies in addressing these temporal and economic challenges, but few studies have explored the feasibility of using such data for genetics research. The main objective of this study was to determine the association of two genetic variants located on chromosome 9p21 conferring susceptibility to coronary heart disease and type 2 diabetes with a variety of clinical phenotypes derived from the electronic health record in a population of morbidly obese patients. Data on more than 100 clinical measures including diagnoses, laboratory values, and medications were extracted from the electronic health records of a total of 709 morbidly obese (body mass index (BMI) ≥ 40 kg/m2) patients. Two common single nucleotide polymorphisms located at chromosome 9p21 recently linked to coronary heart disease and type 2 diabetes (McPherson et al. Science 316:1488–1491, 2007; Saxena et al. Science 316:1331–1336, 2007; Scott et al. Science 316:1341-1345, 2007) were genotyped to assess statistical association with clinical phenotypes. Neither the type 2 diabetes variant nor the coronary heart disease variant was related to any expected clinical phenotype, although high-risk type 2 diabetes/coronary heart disease compound genotypes were associated with several coronary heart disease phenotypes. Electronic health records may be efficient sources of data for validation studies of genetic associations.

This study was conducted to evaluate door-to-treatment times before and after the implementation of a rapid triage and transfer system for patients with ST-elevation myocardial infarction transferred from community hospitals to a rural angioplasty center for primary percutaneous coronary intervention (PCI). The system was developed in late 2004 and implemented at a rural percutaneous coronary intervention center in early 2005. Helicopter transport was available for 97% of requests for transfer from community hospitals. All patients with ST-elevation myocardial infarction transferred during 2004 and 2005 (n=226) were evaluated with respect to presentation and treatment times. Time from community hospital presentation to wire crossing decreased during the study from 205 to 105 minutes (p=0.0001). One fourth of patients were treated90 minutes after presentation, and 2/3 were treated in120 minutes. In conclusion, the implementation of a rapid triage, transfer, and treatment protocol can achieve a significant shortening of presentation-to-treatment times. Efficient community hospitals working with an efficient angioplasty center can achieve presentation-to-wire crossing times of90 minutes for some patients.

Oncogenic ras is known to inhibit cell death and growth inhibitory genes and activate prosurvival genes. Proapoptotic gene PAR-4, has been found to be downregulated by oncogenic ras. Since pancreatic tumors harbor a high incidence of K-ras point mutations, we hypothesized that oncogenic K-ras might influence the function and expression of PAR-4. PAR-4 expression levels were analyzed in 4 established pancreatic tumor cell lines, 10 normal pancreatic tissues, 44 frozen tumor tissues and 25 paraffin-embedded pancreatic adenocarcinoma samples by Real Time RT-PCR, Western blot analysis and immunohistochemistry. K-ras mutational status was analyzed by allele-specific oligonucleotide-hybridization. Expression levels of PAR-4 were correlated with the K-ras mutational status and clinical characteristics. Further, modulation of endogenous PAR-4 was tested by transiently expressing oncogenic ras in a wild-type K-ras pancreatic cancer cell line, BxPC-3. Three cell lines with K-ras mutations showed low levels of PAR-4 when compared to a normal pancreatic tissue. Of 44 frozen tumors, 16 showed appreciable upregulation of Par mRNA and 27 showed significant downregulation of PAR-4 mRNA when compared to normal pancreatic tissue and 1 had levels equivalent to normal pancreatic tissue. Of 25 paraffin-embedded tumors, 9 showed downregulation of PAR-4 protein and this downregulation of PAR-4 correlated significantly with K-ras mutational status (p < 0.00002). In addition, the presence of PAR-4 mRNA or protein expression in pancreatic tumors correlated with prolonged survival. Transient overexpression of oncogenic ras in wild-type K-ras BxPC-3 cells significantly downregulated the endogenous PAR-4 protein levels and conferred accelerated growth. Thus, downregulation or loss of PAR-4 expression by oncogenic ras may provide a selective survival advantage for pancreatic tumors, through inhibition of proapoptotic pathway mediated by PAR-4.

The epidemiology of post-gastric bypass surgery hypoglycemia (PGBH) is incompletely understood. This study aimed to evaluate the risk of PGBH among nondiabetic patients and associated factors.A cohort study of nondiabetic patients who underwent Roux-en-Y gastric bypass (RYGB) was conducted. PGBH was defined by any postoperative record of glucose 60 mg/dL, diagnosis of hypoglycemia, or any medication use for treatment of PGBH. Kaplan-Meier analysis was used to describe PGBH occurrence, log-rank tests, and Cox regression to examine associated factors.Of the 1,206 eligible patients, 86% were female with mean age of 43.7 years, mean preoperative BMI of 48.7 kg/m(2) , and a mean follow-up of 4.8 years. The cumulative incidence of hypoglycemia at 1 and 5 years post-RYGB was 2.7% and 13.3%, respectively. Incidence of PGBH was identified in 158 patients and was associated with lower preoperative BMI (P = 0.048), lower preoperative HbA1c (P = 0.012), and higher 6-month percent of excess body weight loss (%EWL) (P = 0.001). A lower preoperative HbA1c (HR = 1.73, P = 0.0034) and higher 6-month %EWL (HR = 1.96, P = 0.0074) remained independently correlated with increased risk for PGBH in multi-regression analysis.The 5-year incidence of PGBH among nondiabetic individuals was 13.3% and was associated with a lower preoperative HbA1c and greater weight loss at 6 months following surgery.