Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec.

BACKGROUND: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. METHODS: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. RESULTS: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. CONCLUSIONS: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.

Learning from discordance in patient and physician global assessments of systemic lupus erythematosus disease activity.

OBJECTIVE: Differences have been described between patient and physician assessments of well being in several chronic illnesses, and these differences may affect outcome. Disagreement may lead to dissatisfaction and to behaviors with dangerous consequences. We describe and identify predictors of patient-physician differences on ratings of disease activity in systemic lupus erythematosus (SLE). METHODS: Data collected on 154 patients included age, education, disease duration, and patient and physician global assessments of lupus activity on a 10 cm visual analog scale (VAS), the Health Assessment Questionnaire (HAQ), the Medical Outcome Study Short-Form 36 (SF-36), the Systemic Lupus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM-R), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Multiple linear regression models were performed using patient VAS scores, physician VAS scores, and patient minus physician VAS scores as the dependent variables, and age, disease duration, selected SF-36 and SLAM-R subscales, and SDI as independent variables. RESULTS: Patients were 90% female and 80% Caucasian, with a mean education of 13 +/- 2.8 years and a mean age of 43.1 +/- 13.6 years. The overall mean disease duration was 10.5 +/- 7.8 years. Physicians overscored patients by 2.5 cm in 6% of the cases and patients overscored physicians in 16% of the cases. The best multivariate model to predict overall differences included SF-36 mental health and SLAM-R kidney scores. CONCLUSION: Patient-physician differences may result from a divergence in focus. Patients score lupus activity based on their psychological status, while physicians rely more heavily on the physical effect of the disease.

Recruitment strategies in superiority trials in SLE: lessons from the study of methotrexate in lupus erythematosus (SMILE).

The task of recruiting patients for a research project can prove to be the most difficult aspect of the entire research process. A large portion of the work of research is devoted to the identification of strategies which ensure a successful recruitment of patients. Every researcher has learned from experience the many methods needed to enhance patient enrollment into trials. Superiority trials in SLE have not been frequent in previous years. This paper describes the challenges encountered with the multicentre SMILE trial in progress across Canada. We identify areas where patient recruitment is a problem, potential reasons for the problem, and the results of tactics used to increase enrollment.

Outcomes of total hip and knee replacement: preoperative functional status predicts outcomes at six months after surgery.

OBJECTIVE: To determine whether patients with knee or hip osteoarthritis (OA) who have worse physical function preoperatively achieve a postoperative status that is similar to that of patients with better preoperative function. METHODS: This study surveyed an observational cohort of 379 consecutive patients with definite OA who were without other inflammatory joint diseases and were undergoing either total hip or knee replacement in a US (Boston) and a Canadian (Montreal) referral center. Questionnaires on health status (the Short Form 36 and Western Ontario and McMaster Universities Osteoarthritis Index) were administered preoperatively and at 3 and 6 months postoperatively. Physical function and pain due to OA were deemed the most significant outcomes to study. RESULTS: Two hundred twenty-two patients returned their questionnaires. Patients in the 2 centers were comparable in age, sex, time to surgery, and proportion of hip/knee surgery. The Boston group had more education, lower comorbidity, and more cemented knee prostheses. Patients undergoing hip or knee replacement in Montreal had lower preoperative physical function and more pain than their Boston counterparts. In patients with lower preoperative physical function, function and pain were not improved postoperatively to the level achieved by those with higher preoperative function. This was most striking in patients undergoing total knee replacement. CONCLUSION: Surgery performed later in the natural history of functional decline due to OA of the knee, and possibly of the hip, results in worse postoperative functional status.

Sequestration and microsomal C-25 hydroxylation of [3H]-vitamin D3 by the rat liver.

A study of the vitamin D3 (D3) 25-hydroxylase was undertaken in an in vivo-in vitro model. [3H]-D3 (0.7, 1.0, 10, or 100 nmol/100 g of body weight) was injected into the portal vein and the liver was excised 18 seconds later. The liver homogenate was then submitted to differential centrifugation and the amount of [3H]-D3 incorporated in the subcellular fractions was evaluated. The microsomal fraction was also incubated in vitro and the appearance of [3H]-25-hydroxyvitamin D3 [25(OH)D3] was determined by high performance liquid chromatography (HPLC). Results showed that the fractional liver [3H]-D3 uptake varied between 37 percent and 48 percent of the dose injected. The intracellular distribution of [3H]-D3 showed that most of the vitamin was incorporated into the microsomal fraction (45% to 50% of the intracellular [3H]-D3) except at the highest dose of [3H]-D3 where the cytosolic fraction contained the highest amount (56.4%) of the incorporated vitamin. Mathematical analysis of the intracellular [3H]-D3 distribution showed that the microsomal fraction was the only subcellular fraction that was found to incorporate [3H]-D3 in relation to the total liver uptake of the vitamin. The apparent Michaelis-Menten kinetics of the [3H]-D3-25-hydroxylase showed that with substrate concentration of up to 88.5 nM, the apparent Km and Vmax were 28.2 nM and 25.8 fentomoles (fmol) X min-1 X mg microsomal pro-1, respectively, but the reaction lost considerable efficiency with higher substrate concentrations. With the in vivo-in vitro model used, the cytosolic fraction was not essential for the optimal C-25 hydroxylation of D3. These results show that the endoplasmic reticulum of rat hepatocytes possess a high capacity for D3 incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)