Craig Wood

Patient and Physician Factors Associated With Adherence to Diabetes Medications

Purpose The purpose of this study was to examine the influence of patient and physician psychosocial, sociodemographic, and disease-related factors on diabetes medication adherence. These factors were also examined as effect modifiers of the association between quality of the patient-physician relationship and medication adherence. Methods Data were collected from 41 Geisinger Clinic primary care physicians and 608 of their patients with type 2 diabetes. Adherence to oral hypoglycemic medications was calculated using a medication possession ratio based on physician orders in electronic health records (MPREHR). MPREHR was defined as the proportion of total time in the 2 years prior to study enrollment that the patient was in possession of oral hypoglycemic medications. Linear regression was used to examine the influence of patient- and physician-level factors on adherence. Effect modification of the patient-physician relationship-adherence association was evaluated by adding the main effects of the individual-level factors and their cross-products to the models. Results In adjusted analyses, satisfaction with the physician’s patient education skills, patient beliefs about the need for their medications, and lower diabetes-related knowledge were associated with better adherence to oral hypoglycemic medications. Shorter duration of time with diabetes and taking only oral hypoglycemic medications were also associated with better adherence. Finally, the association between shared decision making and medication adherence was significantly modified by patients’ level of social support. Conclusions This study identified several patient-, physician-, and disease-related factors that should be targeted to maximize the potential for developing tailored adherence-enhancing interventions within the context of a collaborative patient-physician relationship.

Downregulation of PAR-4, a pro-apoptotic gene, in pancreatic tumors harboring K-ras mutation

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.

Body Mass Index, Poor Diet Quality, and Health-Related Quality of Life Are Associated With Mortality in Rural Older Adults

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.

Body mass index and all-cause mortality among older adults

To examine the association between baseline body mass index (BMI, kg/m2) and all‐cause mortality in a well‐characterized cohort of older persons.

Feasibility and Impact of an Evidence-Based Program for Gastric Bypass Surgery

BACKGROUND Health care in the United States is expensive and quality is variable. The aim of this study was to investigate whether our integrated health system, composed of academic hospitals, a practice plan, and a managed care payer, could reliably implement an evidence-based program for gastric bypass surgery. A secondary aim was to evaluate the impact of the program on clinical outcomes. STUDY DESIGN A standardized program for delivery of clinical best-practice elements for patients undergoing initial open or laparoscopic Roux-en-Y gastric bypass was implemented in 2008. Best-practice elements were embedded into the workflow. The best-practice elements were refined after reviewing failures observed during the early implementation period. The study period was divided into 3 groups: group α = year preceding program implementation (control), group β = first year of implementation (unreliable), and group Ω = 2nd to 4th years of implementation (reliable). Outcomes data were collected for all patients who had undergone Roux-en-Y gastric bypass between May 2008 and April 2012 and were compared with a control group from the preceding year using multiple logistic regression analysis. RESULTS Two thousand and sixty-one patients were studied, with no significant demographic differences between study groups. Best-practice elements delivery was 40% in group β, but was >90% for group Ω (p < 0.001). Length of stay for group α was 3.5 days and improved to 2.2 days (p < 0.001) for group Ω. Complications and readmission rates improved considerably with reliable delivery of best-practice elements. CONCLUSIONS Standardization of evidence-based care delivery for Roux-en-Y gastric bypass was feasible and reliable delivery of this pathway improved clinical outcomes.

The associations between diet quality, body mass index (BMI) and health and activity limitation index (HALex) in the Geisinger Rural Aging Study (GRAS)

ObjectivesTo determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults.DesignMultivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting.SettingGeisinger Rural Aging Study, Pennsylvania. Participants: 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. Results: HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60–75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5–24.9.ConclusionsPoor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.

Frequencies of obesity susceptibility alleles among ethnically and racially diverse bariatric patient populations

BACKGROUND Genetic factors likely play a role in obesity and the outcomes after bariatric surgery. Single nucleotide polymorphisms in or near the insulin-induced gene 2 (INSIG-2), fat mass and obesity-associated gene (FTO), melanocortin 4 receptor gene (MC4R), and proprotein convertase subtilisn/kexin type 1 gene (PCSK-1) have been associated with class III obesity in whites. Minimal data are available regarding the genetic susceptibility to obesity in class III obese nonwhites, especially Hispanics. Our objective was to perform a comparative analysis of 4 common genetic variants (INSIG-2, FTO, MC4R, and PCSK-1) associated with obesity in a diverse population of bariatric surgery patients to determine whether a difference exists by ethnicity (white versus Hispanic). The setting of the study was 2 university hospitals in the United States. METHODS Bariatric surgery patients from 2 different institutions were enrolled prospectively, and genotyping was performed. Differences in the distribution of INSIG-2, FTO, MC4R, and PCSK-1 single nucleotide polymorphisms among the different ethnicities (whites and Hispanics) were compared using an additive model (0, 1, or 2 risk alleles). A propensity-matched analysis was used to account for cohort differences. RESULTS A total of 1276 bariatric patients were genotyped for the INSIG-2, FTO, MC4R, and PCSK-1 obesity single nucleotide polymorphisms. Statistically significant differences in FTO, INSIG-2, MC4R, and PCSK-1 were seen using an additive model. FTO, PCSK-1, and MC4R (test for trend) remained significantly different in the propensity analysis. CONCLUSION Significant differences in the frequencies of several common obesity susceptibility variants in or near FTO, PCSK-1, and MC4R were found in white and Hispanic patients with class III obesity undergoing bariatric surgery. Larger studies in more class III obese Hispanics of different nationalities are needed.

Metabolic Health Status and the Obesity Paradox in Older Adults

ABSTRACT 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/m2) 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-interaction <0.001). 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.

Diet-related practices and BMI are associated with diet quality in older adults

OBJECTIVE To assess the association of diet-related practices and BMI with diet quality in rural adults aged ≥74 years. DESIGN Cross-sectional. Dietary quality was assessed by the twenty-five-item Dietary Screening Tool (DST). Diet-related practices were self-reported. Multivariate linear regression models were used to analyse associations of DST scores with BMI and diet-related practices after controlling for gender, age, education, smoking and self- v. proxy reporting. SETTING Geisinger Rural Aging Study (GRAS) in Pennsylvania, USA. SUBJECTS A total of 4009 (1722 males, 2287 females; mean age 81·5 years) participants aged ≥74 years. RESULTS Individuals with BMI < 18·5 kg/m2 had a significantly lower DST score (mean 55·8, 95 % CI 52·9, 58·7) than those individuals with BMI = 18·5-24·9 kg/m2 (mean 60·7, 95 % CI 60·1, 61·5; P = 0·001). Older adults with higher, more favourable DST scores were significantly more likely to be food sufficient, report eating breakfast, have no chewing difficulties and report no decline in intake in the previous 6 months. CONCLUSIONS The DST may identify potential targets for improving diet quality in older adults including promotion of healthy BMI, breakfast consumption, improving dentition and identifying strategies to decrease concern about food sufficiency.

Diet Quality and Body Mass Index Are Associated with Health Care Resource Use in Rural Older Adults

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.