Assessment of the Siksika chronic disease nephropathy-prevention clinic.

OBJECTIVE: To determine if a community-based multifactorial intervention clinic led by a nurse practitioner would improve management of First Nations people at risk of developing chronic kidney disease. DESIGN: Qualitative descriptive study. SETTING: A nephropathy-prevention clinic in Siksika Nation, Alta. PARTICIPANTS: First Nations people with diabetes, hypertension, or dyslipidemia who were referred to the clinic. MAIN OUTCOME MEASURES: Changes in blood pressure (BP), hemoglobin A(1c), and low-density lipoprotein levels, as well as in use of antiplatelet therapy, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications, and statin therapy. RESULTS: Members of the Siksika Nation were treated according to clinical practice guidelines. A total of 78 patients had at least 2 visits to the clinic and were included in this analysis (61.5% were women; mean age 56 years). Among those initially above target, a significant reduction was achieved in mean hemoglobin A(1c) (0.96%; P < .01), systolic BP (15.84 mm Hg; P < .05), diastolic BP (7.16 mm Hg; P < .001), and low-density lipoprotein (0.62 mmol/L; P < .01) levels. There was a significant increase in the proportion of patients with clinical indications who were treated with acetylsalicylic acid (42.4%; P < .01), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications (35.9%; P < .01), or statin therapy (35.9%; P < .01). CONCLUSION: A community-based, nurse practitioner-led clinic can improve many clinically relevant factors in patients at risk of developing chronic kidney disease. Studies have shown that achieving treatment targets is associated with a reduced risk of early death and cardiovascular events; the effect in the First Nations population on these hard clinical end points remains to be determined.

Validating a case definition for chronic kidney disease using administrative data.

BACKGROUND: Administrative data are commonly used for surveillance of chronic medical conditions. The purpose of this study was to determine the validity of an algorithm derived from administrative data for identifying chronic kidney disease (CKD) compared to the reference standard of estimated glomerular filtration rate (eGFR). METHODS: We identified adults from the province of Alberta with at least two outpatient serum creatinine measurements within a 1-year time period. Validity indices were estimated for CKD using up to 3 years of administrative data (physician billing claims and hospital discharge abstracts) for various case-definition combinations. For each algorithm, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated against two reference standard definitions of CKD (two eGFR measurements <60 mL/min/1.73m(2) or mean eGFR < 30 mL/min/1.73m(2)). RESULTS: A total of 321 293 eligible subjects were identified. Irrespective of the algorithm, sensitivities for defining CKD (eGFR < 60 mL/min/1.73m(2)) using administrative codes were low. A case-definition algorithm employing two physician claims or one hospitalization within a 2-year period had sensitivity of 19.4%, specificity of 97.2%, PPV of 60.1% and NPV of 84.8% for detecting CKD. Estimates of sensitivity were higher when <30 mL/min/1.73m(2) was used as the reference standard, although PPVs were lower and consistently less than 50%. CONCLUSION: These results, using eGFR as a reference standard, suggest that administrative data have insufficient sensitivity and PPV for CKD surveillance, although they may be useful when highly specific algorithms are required for research purposes.

Polycystic ovary syndrome: validated questionnaire for use in diagnosis.

OBJECTIVE: To construct and validate a questionnaire for use in diagnosis of polycystic ovary syndrome (PCOS). DESIGN: All participants completed a questionnaire, which asked clinical questions designed to assist in the diagnosis of PCOS, before their appointments with an endocrinologist. Following completion of the questionnaire, the endocrinologist (blinded to the answers) made or excluded a diagnosis of PCOS using clinical criteria and biochemical data as indicated. Questions were then evaluated for their power to predict PCOS, and a model was constructed using the most reliable items to establish a system to predict a diagnosis of PCOS. SETTING: An outpatient reproductive endocrinology clinic in Calgary, Alta. PARTICIPANTS: Adult women patients who had been referred to the clinic. Fifty patients with PCOS and 50 patients without PCOS were included in the study. MAIN OUTCOME MEASURES: Demographic information, medical history, related diagnoses, menstrual history, and fertility history. RESULTS: A history of infrequent menses, hirsutism, obesity, and acne were strongly predictive of a diagnosis of PCOS, whereas a history of failed pregnancy attempts was not useful. A history of nipple discharge outside of pregnancy strongly predicted no diagnosis of PCOS. We constructed a 4-item questionnaire for use in diagnosis of PCOS; the questionnaire yielded a sensitivity of 85% and a specificity of 85% on multivariate logistic regression and a sensitivity of 77% and a specificity of 94% using the 4-item questionnaire. Predictive accuracy was validated using a second sample of 117 patients, in addition to internal validation using bootstrap analysis. CONCLUSION: We have constructed a simple clinical tool to help diagnose PCOS. This questionnaire can be easily incorporated into family physicians' busy practices.

Predictors of adherence to supervised and unsupervised exercise in the Alberta Physical Activity and Breast Cancer Prevention Trial.

BACKGROUND: Few studies have examined the predictors of adherence separately for supervised and unsupervised exercise or in postmenopausal women over an extended time period. Here, we report the predictors of exercise adherence in the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial. METHODS: The ALPHA trial randomized 160 postmenopausal women in Calgary and Edmonton, Canada to an exercise intervention that consisted of an average of 200 min/wk of supervised (123 minutes) and unsupervised (77 minutes) exercise over a 1-year period. Baseline data were collected on demographic, health-related fitness, quality of life, and motivational variables from the theory of planned behavior. RESULTS: Participants completed an average of 95% of their supervised exercise and 79% of their unsupervised exercise. In multivariate analyses, 8.1% (P=.001) of the variance was explained for supervised exercise by being from Edmonton (ß=0.22; P=.004) and older (ß=0.15; P=.050). For unsupervised exercise, 21.1% (P<.001) of the variance was explained by being from Calgary (ß=-0.39; P<.001), having a family history of breast cancer (ß=0.21; P=.003), and having higher vitality (ß=0.19; P=.011). CONCLUSIONS: Predictors of adherence may differ for supervised and unsupervised exercise, moreover, predicting adherence to supervised exercise may be particularly difficult in well-controlled efficacy trials.

High stromal carbonic anhydrase IX expression is associated with decreased survival in P16-negative head-and-neck tumors.

PURPOSE: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. METHODS AND MATERIALS: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). RESULTS: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. CONCLUSIONS: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

Prognostic significance of p16 in locally advanced squamous cell carcinoma of the head and neck treated with concurrent cisplatin and radiotherapy.

BACKGROUND: Human papillomavirus (HPV)-related squamous cell cancer of the head and neck (SCCHN) has emerged as a distinct clinical entity. The expression of p16 protein can be used as a surrogate for HPV status. METHODS: p16 immunohistochemistry (IHC) was assessed in archival paraffin-embedded material for 55 patients with locally advanced SCCHN treated with a uniform regimen of cisplatin and radiation. HPV status was assessed by colorimetric in situ hybridization (CISH) and polymerase chain reaction (PCR). RESULTS: Compared with p16- and HPV-negative patients, the p16- and HPV-positive patients had improved overall survival, disease-free survival, and locoregional recurrence rates. CONCLUSIONS: p16 IHC may serve as a useful surrogate and prognostic marker for patients with HPV-related SCCHN treated with cisplatin and radiation.

Mammographic density change with 1 year of aerobic exercise among postmenopausal women: a randomized controlled trial.

BACKGROUND: The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk. Mammographic density, a secondary outcome, is reported here. METHODS: The ALPHA Trial was a parallel group randomized controlled trial conducted between May 2003 and July 2007. Postmenopausal, sedentary women ages 50 to 74 years (n = 320) were evenly randomized to aerobic exercise (45 minutes, 5 days per week) or control (usual life-style) for 1 year. Dense fibroglandular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computer-assisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements. RESULTS: Nondense volume decreased in the exercise group relative to the control group (difference between groups = -38.5 cm(3); 95% confidence interval, -61.6 to 15.4; P = 0.001). Changes in total body fat accounted for this decrease. Changes in dense area and dense volume, measures that have previously been associated with breast cancer risk, were not significantly different between the groups (P > or = 0.26). CONCLUSIONS: Achieving changes in mammographic measures may require more exercise or a study population with higher baseline levels of sex hormones or a wider range of mammographic density. The data from this study, however, suggest that the protective effect of exercise on breast cancer risk may operate through a mechanism other than mammographic density.

Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium.

BACKGROUND: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. METHODS: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. RESULTS: The five polymorphisms were not associated with ovarian carcinoma overall (P(trend) > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P(heterogeneity) = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). CONCLUSIONS: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. IMPACT: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity.

BACKGROUND: Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. METHODS: The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m(2) during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence-free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. RESULTS: Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan-Meier overall, disease-specific, and locoregional recurrence-free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. CONCLUSION: This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules.