Group Health & Wellness Coaching: development and validation of the required competencies.

BACKGROUND: As the popularity and demonstrated effectiveness of Health and Wellness Coaching (HWC) continue to grow to address chronic disease prevalence worldwide, delivery of this approach in a group format is gaining traction, particularly in healthcare. Nonetheless, very little empirical work exists on group coaching and there are currently no published competencies for Group Health and Wellness Coaching (GHWC). METHODS: We used a well-established two-phase (Development and Judgment) process to create and validate GHWC competencies with strong content validity. RESULTS: Seven highly qualified Subject Matter Experts systematically identified and proposed the GHWC competencies, which were then validated by 78 National Board Certified Health and Wellness Coaches (NBC-HWCs) currently practicing GHWC who rated the importance and use frequency of each one. The validation study led to 72 competencies which are organized into the structure and process of GHWC. CONCLUSIONS: GHWC requires not only coaching skills, but significant group facilitation skills to guide the group process to best support members in maximizing health and well-being through self-directed behavioral change. As the presence of HWC continues to grow, it is imperative that GHWC skill standards be accepted and implemented for the safety of the public, the effectiveness of the intervention, and the value analysis of the field. Such standards will guide curriculum development, allow for a more robust research agenda, and give practical guidance for health and wellness coaches to responsibly run groups. High quality standards for GHWC are particularly needed in health care, where a Level III Current Procedural Terminology (CPT®) code for GHWC has been approved in the United States since 2019 and reimbursement of such has been approved by the Centers for Medicare and Medicaid for 2024.

Comparative effectiveness of revascularization strategies.

BACKGROUND: Questions persist concerning the comparative effectiveness of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG). The American College of Cardiology Foundation (ACCF) and the Society of Thoracic Surgeons (STS) collaborated to compare the rates of long-term survival after PCI and CABG. METHODS: We linked the ACCF National Cardiovascular Data Registry and the STS Adult Cardiac Surgery Database to claims data from the Centers for Medicare and Medicaid Services for the years 2004 through 2008. Outcomes were compared with the use of propensity scores and inverse-probability-weighting adjustment to reduce treatment-selection bias. RESULTS: Among patients 65 years of age or older who had two-vessel or three-vessel coronary artery disease without acute myocardial infarction, 86,244 underwent CABG and 103,549 underwent PCI. The median follow-up period was 2.67 years. At 1 year, there was no significant difference in adjusted mortality between the groups (6.24% in the CABG group as compared with 6.55% in the PCI group; risk ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00). At 4 years, there was lower mortality with CABG than with PCI (16.4% vs. 20.8%; risk ratio, 0.79; 95% CI, 0.76 to 0.82). Similar results were noted in multiple subgroups and with the use of several different analytic methods. Residual confounding was assessed by means of a sensitivity analysis. CONCLUSIONS: In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI. (Funded by the National Heart, Lung, and Blood Institute.).

Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry.

BACKGROUND: The purpose of this study was to develop a long-term model to predict mortality after percutaneous coronary intervention in both patients with ST-segment elevation myocardial infarction and those with more stable coronary disease. METHODS AND RESULTS: The American College of Cardiology Foundation CathPCI Registry data were linked to the Centers for Medicare and Medicaid Services 100% denominator file by probabilistic matching. Preprocedure demographic and clinical variables from the CathPCI Registry were used to predict the probability of death over 3 years as recorded in the Centers for Medicare and Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518 195 patients aged ≥65 years undergoing first percutaneous coronary intervention in the CathPCI Registry were successfully linked to Centers for Medicare and Medicaid Services data. This study population was randomly divided into 60% derivation and 40% validation cohorts. Median follow-up was 15 months, with mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years, respectively. Twenty-four characteristics related to demographics, clinical comorbidity, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. The C indices in the validation cohorts for patients with and without ST-segment elevation myocardial infarction were 0.79 and 0.78. The model calibrated well across a wide range of predicted probabilities. CONCLUSIONS: On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention.

Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study).

BACKGROUND: Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. We estimate a long-term survival model using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and Centers for Medicare and Medicaid Services. METHODS AND RESULTS: The final study cohort included 348 341 isolated coronary artery bypass grafting patients aged ≥65 years, discharged between January 1, 2002, and December 31, 2007, from 917 Society of Thoracic Surgeons-participating hospitals, randomly divided into training (n=174 506) and validation (n=173 835) samples. Through linkage with Centers for Medicare and Medicaid Services claims data, we ascertained vital status from date of surgery through December 31, 2008 (1- to 6-year follow-up). Because the proportional hazards assumption was violated, we fit 4 Cox regression models conditional on being alive at the beginning of the following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2 years. Kaplan-Meier-estimated mortality was 3.2% at 30 days, 6.4% at 180 days, 8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for predicting overall survival time was 0.732. Some risk factors (eg, emergency status, shock, reoperation) were strong predictors of short-term outcome but, for early survivors, became nonsignificant within 2 years. The adverse impact of some other risk factors (eg, dialysis-dependent renal failure, insulin-dependent diabetes mellitus) continued to increase. CONCLUSIONS: Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling.

The association between inflammation-related genes and serum androgen levels in men: the prostate, lung, colorectal, and ovarian study.

BACKGROUND: Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes. METHODS: In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17ß-diol glucuronide [3αdiol G], and 4-androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based P values were generated using an adaptive rank truncated product (ARTP) method. RESULTS: Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value <0.1) in both SNP and gene-based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q-value = 0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSION: These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk.

Topical anaesthetics for repair of dermal laceration.

BACKGROUND: Topical local anaesthetics are recognized as providing effective analgesia for numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned due to concern about adverse effects, and so novel preparations of cocaine-free anaesthetics have been developed. OBJECTIVES: To compare the efficacy and safety of infiltrated local anaesthetics with those of topical local anaesthetics for repair of dermal lacerations and to evaluate the efficacy and safety of various single or multi-component topical anaesthetics to identify cocaine-free topically applied local anaesthetics that may provide equivalent analgesia to those containing cocaine. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10); MEDLINE (1966 to November 2010); EMBASE (1980 to November 2010); CINAHL (1982 to November 2010); and reference lists of articles. We also handsearched selected journals, reviewed abstracts presented at international society meetings, reviewed metaregisters of ongoing trials and contacted manufacturers and researchers in the field. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of torn skin in adult and paediatric patients. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse event information from the trials. MAIN RESULTS: We included 23 RCTs involving 3128 patients. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data in all but one outcome, pain scores using a visual analogue scale. The majority of trials that compared infiltrated and topical anaesthetics are at high risk of bias, which is likely to affect the interpretation of the results. Several cocaine-free topical anaesthetics were found to provide effective analgesic efficacy. However, the data regarding the efficacy of each topical agent is mostly based upon single comparisons, in trials that have unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one case after application of topical tetracaine-adrenaline-cocaine (TAC) where a total of 1042 patients were exposed. No serious complications were reported in any of the patients treated with either cocaine-based or cocaine-free topical anaesthetics. AUTHORS' CONCLUSIONS: Based on mostly descriptive analysis, topical anaesthetics are possibly an efficacious, non-invasive means of providing analgesia prior to suturing of dermal lacerations. However, additional well designed RCTs with low risk of bias are necessary before definitive conclusions can be made.

Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer.

Endogenous sex hormones and the risk of prostate cancer: a prospective study.

Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (Delta4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha-diolG). A total of 727 incident Caucasian prostate cancer cases (age >/= 65 years, N = 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p(trend) = 0.01), mostly related to risk in older men (>/=65 years, p(trend) = 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.50-5.09]. No clear patterns were noted for Delta4-A and 3alpha-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. (c) 2008 Wiley-Liss, Inc.

Menstrual and reproductive factors in association with lung cancer in female lifetime nonsmokers.

Cigarette smoking is irrefutably the strongest risk factor for lung cancer; however, approximately 25% of cases worldwide occur among nonsmokers. The age-adjusted annual incidence rate of lung cancer in Shanghai, a region where relatively few women smoke cigarettes, is one of the highest in the world. To help further elucidate the etiology of lung cancer among nonsmokers, the authors examined hormonal factors among women who were lifetime nonsmokers. They analyzed data from the prospective Shanghai Women's Health Study, which recruited Chinese women aged 40-70 years between 1996 and 2000 from selected urban communities. The current analysis included 71,314 women (n = 220 cases) who were lifetime nonsmokers and had no history of cancer at baseline. Later age at menopause (> or =51 vs. <46 years; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.40, 1.00), longer reproductive period (> or =36 vs. <31 years; HR = 0.60, 95% CI: 0.39, 0.93), higher parity (> or =4 vs. 0 children; HR = 0.42, 95% CI: 0.19, 0.90), and intrauterine device use (HR = 0.59, 95% CI: 0.41, 0.86) were associated with decreased risks of lung cancer. This large prospective study suggests a potential role for hormonal factors in the etiology of lung cancer among nonsmoking women.

Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

OBJECTIVE: A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. METHODS: We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). CONCLUSION: In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.

IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.

Increased Body Mass Index Associated with Increased Risky Sexual Behaviors.

STUDY OBJECTIVE: The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. In the current study we examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 through 2013. INTERVENTION AND MAIN OUTCOME MEASURES: Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared with clinically assessed BMI. RESULTS: BMI was positively associated with number of sexual partners (P = .001) and history of attempted anal intercourse (P = .002). An inverse association was observed with age at first anal intercourse (P = .040). CONCLUSION: In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. Results of this study suggest that overweight and obese adolescents are a vulnerable population who might need targeted sexual health counseling.

Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer.

Exposure to estrogens is a likely cause of endometrial cancer, but the means by which estrogens exert this effect are not entirely clear. One hypothesis is that certain estrogen metabolites bind to the DNA, forming bulky adducts that damage the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such damage may increase her risk of endometrial cancer. We conducted a population-based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer. Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420) were selected using random-digit dialing (ages 50-65 years) and by random selection from Health Care Financing Administration data files (ages 66-69 years). Genotyping assays were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a), ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer.

Topical anesthetics for dermal instrumentation: a systematic review of randomized, controlled trials.

STUDY OBJECTIVE: We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics (EMLA). METHODS: We conducted a systematic review of randomized, controlled trials. Relevant literature was identified through searches of MEDLINE, Cochrane Central Register of Controlled Trials, and the Excerpta Medica Database Drugs and Pharmacology. We limited the type of procedures to puncture of intact skin with a needle. The primary outcome was analgesic efficacy, reflected in the patient's self-report of pain intensity during dermal instrumentation. Where possible, quantitative methods were used to summarize the results. RESULTS: We identified 25 randomized controlled trials including 2,096 subjects. The results of the trials comparing the efficacy of EMLA with infiltrated local anesthetic were inconsistent. Qualitative analysis demonstrated comparable analgesic efficacy between liposome-encapsulated lidocaine and EMLA. The weighted mean difference in 100-mm visual analogue scale pain scores favored topical tetracaine over EMLA (-8.1 mm; 95% confidence interval -15.6 mm to -0.6 mm). Liposome-encapsulated tetracaine provided greater analgesia than EMLA according to the weighted mean difference in 100-mm visual analogue scale scores (-10.9 mm; 95% confidence interval -15.9 mm to -5.9 mm). CONCLUSION: EMLA may be an effective, noninvasive means of analgesia before dermal procedures. However, we identified 3 topical anesthetics that are at least as efficacious as EMLA: tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lidocaine. Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA.

Comparative efficacy and costs of various topical anesthetics for repair of dermal lacerations: a systematic review of randomized, controlled trials.

STUDY OBJECTIVES: To compare the efficacy of infiltrated local anesthesia with topical anesthesia for repair of dermal laceration, to analyze the efficacy of single or multicomponent topical anesthetics, and to identify topical formulations that are potentially less costly and equally efficacious as cocaine-containing topical anesthetics. DESIGN: Systematic review of randomized controlled trials. SETTING: University-affiliated hospital. PATIENTS: Pediatric and adult subjects. MEASUREMENTS AND MAIN RESULTS: Twenty-two trials that randomized more than 3000 patients were identified. The majority of studies demonstrated equivalent or superior analgesic efficacy for topical formulations compared with conventional intradermal infiltration. We found that cocaine is not a mandatory component of topical anesthesia. The literature discloses no significant difference in anesthetic efficacy between topical tetracaine-epinephrine-cocaine and each of the following 6 cocaine-free formulations: lidocaine-epinephrine-tetracaine, lidocaine-epinephrine, tetracaine-phenylephrine, tetracaine-lidocaine-phenylephrine, bupivicaine-norepinephrine, or prilocaine-phenylephrine. CONCLUSION: Topical anesthetics are an efficacious, noninvasive means of providing analgesia before suturing of dermal lacerations. The use of cocaine-containing topical anesthetics can no longer be justified in light of its high cost and potential adverse effects. We have summarized the evidence, mostly favorable, supporting the use of various non-cocaine-containing topical anesthetics.

Corticotropin-releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone.

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values>0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

Circulating adipokine levels and endometrial cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial.

BACKGROUND: Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively. METHODS: We conducted a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels. RESULTS: Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 = 0.48; 95% CI, 0.29-0.80); Ptrend < 0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60-4.79); Ptrend < 0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were stronger and remained significant after adjustment for estradiol and BMI [0.25 (0.08-0.75); Ptrend = 0.01 and 4.72 (1.15-19.38); Ptrend = 0.02, respectively]. Nonsignificant positive associations were observed for visfatin. CONCLUSION: Adipokines may influence endometrial cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT. IMPACT: Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity-endometrial cancer association.

Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.

BACKGROUND: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. IMPACT: These results might provide some clues for the strong link between 8q24 and prostate cancer risk.

Anthropometric measurements, physical activity, and the risk of symptomatic gallstone disease in Chinese women.

PURPOSE: Gallstone disease is more common among overweight individuals, particularly in women. We conducted a cross-sectional case-control study of Chinese women nested in the Shanghai Women's Health Study (SWHS) to evaluate the association of gallstone disease with body mass index (BMI), waist to hip ratio (WHR), and physical activity (PA). METHODS: The study included 8,485 women with self-reported, physician-diagnosed, prevalent gallstone disease and 16,970 frequency-matched controls by birth year and age at gallstone diagnosis (4-year intervals). Information on height, weight history, waist and hip circumferences, physical activities, and other exposures was obtained by in-person interview. RESULTS: : Usual BMI (p trend < 0.001) and WHR (p trend < 0.001) were both related to a high prevalence of gallstone disease, and a significant interaction between BMI and WHR on gallstone risk was found (odds ratio [OR] = 3.82, 95%CI [95% confidence interval] 2.47-5.23 for those with both highest BMI and WHR relative to those with lowest BMI and WHR, p interaction = 0.03). Gallstone risk was positively associated with cumulative occupational sitting time (p trend = 0.01) and inversely associated with occupational cumulative energy expenditure (p trend = 0.03) as well as with household PA (p trend = 0.02). CONCLUSIONS: Our findings further support that overall and central excessive adiposity is an independent risk factor for gallstones in women. In addition, regardless of adiposity level, being physically active may ameliorate the risk of this disease.

Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association.

OBJECTIVES: Certain nucleotide excision repair (NER) genotypes appear to be associated with an altered risk of endometrial cancer. These associations could be modified by characteristics and exposures that themselves influence risk of disease. METHODS: We conducted a population-based case-control study in western Washington State to address the role of specific NER genotypes in conjunction with relevant exposures, such as postmenopausal hormone therapy, obesity, parity, oral contraceptive use, and cigarette smoking on risk of endometrial cancer. Case women (n=371), ages 50-69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n=420), matched to cases on age and county of residence, were selected using random-digit dialing (ages 50-65) and random selection from HCFA data files (ages 66-69). RESULTS: Risk of endometrial cancer was not associated with ERCC1, ERCC2 (XPD), ERCC4 (XPF), or ERCC5 (XPG) genotype. A reduced risk of endometrial cancer was observed with presence of the XPA g23a variant allele, but only among women with a history of oral contraceptive use (OR 0.47, 95% CI 0.32-0.69). A decreased risk associated with carriage of at least one variant allele for both XPC A499V and XPC K939Q was restricted to women with BMI<30 kg/m2 (OR 0.45, 95% CI 0.25-0.82). The size of the association between these genotypes and risk of endometrial cancer did not differ by postmenopausal hormone use, parity, or smoking. CONCLUSIONS: Our study provides limited evidence for interactions between NER genotypes and DNA damage-causing exposures in the etiology of endometrial cancer. Subsequent studies are needed to confirm the observed associations.