G. Craig Wood

Urinary incontinence in women: variation in prevalence estimates and risk factors.

OBJECTIVE: To understand variation in prevalence of urinary incontinence (UI) and risk factors, given different definitions. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: III

A Role for Fibroblast Growth Factor 19 and Bile Acids in Diabetes Remission After Roux-en-Y Gastric Bypass

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.

Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a retrospective cohort study

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, HbA1c 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<0·0001). Kaplan-Meier analysis showed that 88% (95% CI 83–92%) of patients who scored 0–2, 64% (58–71%) of those who scored 3–7, 23% (13–33%) of those who scored 8–12, 11% (6–16%) of those who scored 13–17, and 2% (0–5%) of those who scored 18–22 achieved early remission (partial or complete). As in the primary cohort, the proportion of patients achieving remission in the replication cohorts was highest for the lowest scores, and lowest for the highest scores. 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.

Employment and work impact of chronic migraine and episodic migraine

Objective: To determine work impact of chronic migraine (CM) versus episodic migraine (EM). Methods: Data were from the 2005 American Migraine Prevalence and Prevention study, a longitudinal population survey of more than 11,000 migraineurs. Lost productive time (LPT) was measured as missed work hours plus reduced productivity hour equivalents. Results: Those with CM were 19% less likely to be working for pay compared with migraineurs with ≤3 headache-days/month. On average, those with CM lost 4.6 hours/wk from headache compared with 1.1 hours for those with ≤3 headache-days/month. Those with 10 to 14 headache-days/month or with CM accounted for 9.1% of employed migraineurs, 20.8% of work-related LPT, and 35% of the overall lost work time when considering medical leave and unemployment. Conclusions: The work impact of CM and high frequency EM will be underestimated if employment status is not measured.

Preoperative weight loss before bariatric surgery.

HYPOTHESIS Preoperative weight loss reduces the frequency of surgical complications in patients undergoing bariatric surgery. DESIGN Review of records of patients undergoing open or laparoscopic gastric bypass. SETTING A comprehensive, multidisciplinary obesity treatment center at a tertiary referral center that serves central Pennsylvania. PATIENTS A total of 881 patients undergoing open or laparoscopic gastric bypass from May 31, 2002, through February 24, 2006. INTERVENTION All preoperative patients completed a 6-month multidisciplinary program that encouraged a 10% preoperative weight loss. MAIN OUTCOME MEASURES Loss of excess body weight (EBW) and total and major complication rates. RESULTS Of the 881 patients, 592 (67.2%) lost 5% or more EBW and 423 (48.0%) lost more than 10% EBW. Patients referred for open gastric bypass (n = 466) were generally older (P < .001), had a higher body mass index (P < .001), and were more often men (P < .001) than those undergoing laparoscopic gastric bypass (n = 415). Total and major complication rates were higher in patients undergoing open gastric bypass (P < .001 and P = .03, respectively). Univariate analysis revealed that increasing preoperative weight loss is associated with reduced complication frequencies for the entire group for total complications (P =.004) and most likely for major complications (P = .06). Controlling for age, sex, baseline body mass index, and type of surgery in a multiple logistic regression model, increased preoperative weight loss was a predictor of reduced complications for any (P =.004) and major (P = .03) complications. CONCLUSION Preoperative weight loss is associated with fewer complications after gastric bypass surgery.

Clinical factors associated with weight loss outcomes after Roux‐en‐Y gastric bypass surgery

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 preoperative clinical variables were associated with weight loss following Roux‐en‐Y gastric bypass (RYGB) surgery.

Risk Factors Associated With Mortality After Roux-en-Y Gastric Bypass Surgery

Objective:We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery. Background: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. Methods: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. Results: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) (P < 0.0001), increasing age (P < 0.005), male gender (P < 0.001), pulmonary hypertension (P < 0.0001), congestive heart failure (P = 0.0008), and liver disease (P = 0.038). When the RYGB risk score was applied, a significant trend (P < 0.0001) between increasing risk score and mortality rate is found. Conclusions: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.

Predictors of first-fill adherence for patients with hypertension.

BACKGROUND Between the promise of evidence-based medicine and the reality of inadequate patient outcomes lies patient adherence. Studies of prescription adherence have been hampered by methodologic problems. Most rely on patient self-report of adherence or cross-sectional data of plan-wide prescription fills to estimate patient-level adherence. METHODS We conducted a retrospective cohort study and linked individual patient data for incident prescriptions for antihypertensive medications from electronic health records (EHRs) to claims data obtained from the patients insurance plan. Clinical data were obtained from the Geisinger Clinic, a 41 site group practice serving central and northeastern Pennsylvania with an EHR in use since 2001. Adherence was defined as a prescription claim generated for the first-fill prescription within 30 days of the prescribing date. RESULTS Of the 3,240 patients written a new, first-time prescription for an antihypertensive medication, 2,685 (83%) generated a corresponding claim within 30 days. Sex, age, therapeutic class, number of other medications prescribed within 10 days of the antihypertensive prescription, number of refills, co-pay, comorbidity score, baseline blood pressure (BP), and change in BP were significantly associated with first-fill rates (P < 0.05). CONCLUSIONS Patients who are older, female, have multiple comorbidities, and/or have relatively lower BPs may be less likely to fill a first prescription for antihypertensive medications and may be potential candidates for interventions to improve adherence to first-fill prescriptions.

Efficacy and Toxicity of Adjuvant Chemotherapy in Elderly Patients with Colon Carcinoma: A 10-Year Experience of the Geisinger Medical Center.

Although the benefit from adjuvant chemotherapy has been established clearly in patients with Stage III colon carcinoma, the degree to which elderly patients with colon carcinoma can tolerate such therapy generally has remained unknown.

High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery.

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/m2) 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 <50 kg/m2, with evidence of a dosage effect, which was not present in individuals with initial BMI ≥50 kg/m2. Differences in metabolic rate, binge eating behavior, and other clinical parameters were not associated with genotype. These data suggest that response to a surgical weight loss intervention is influenced by genetic susceptibility and BMI.