Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer.

CONTEXT: Hereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer. OBJECTIVE: To determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry. DESIGN, SETTING, AND PATIENTS: Thirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years. MAIN OUTCOME MEASURES: Classification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations. RESULTS: Thirteen mutations (6 novel) were identified in 15 of the 38 families (40% detection rate). The 1137G>A splicing mutation and the 1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G>A (R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%-91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% (95% CI, 29%-94%). CONCLUSIONS: Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.

Men considering a hypothetical treatment for prostate cancer: a comparison to patients.

BACKGROUND: In facilitating informed decision making about PSA screening, men are often asked to consider the potential consequences of the test, including a diagnosis of prostate cancer and how they would want to be treated. However, there is no empirical evidence thus far demonstrating that men are able to consider this hypothetical situation in a realistic manner. PURPOSE: To compare the features (attributes) of treatments that are important to non-patient men considering a hypothetical diagnosis of prostate cancer with those deemed important to men actually diagnosed with early-stage disease. METHODS: Two groups of men went through a decision aid interview to help them choose between treatment options for early-stage prostate cancer: non-patient men who imagined themselves to be diagnosed with the disease, and newly diagnosed patients. During the interview participants identified features of the treatment and disease that were important to their decisions. RESULTS: The percentage of non-patients and patients that thought particular attributes were important was correlated: r (33) = 0.77, p < 0.01. The effects on bladder and bowel functioning were considered important to >or=50% of each group. In addition to the 22 attributes initially presented, 49% of non-patients and 67% of patients identified additional attributes as being important to their decision. Eight (42%) of the 19 additional attributes were identified by non-patients and patients alike. CONCLUSIONS: The group of non-patient men provided a close approximation to the group of newly diagnosed men with respect to the attributes identified as being important to their treatment decisions for early-stage prostate cancer, suggesting that the consideration of what is important to the decision by non-patient men is realistic.

Health care providers' and patients' perspectives on care in HIV ambulatory clinics across Ontario.

This descriptive study represents one component of a larger project that examined the perceptions of current and best-care practices in HIV ambulatory clinics across Ontario by health care providers and patients living with HIV/AIDS. Focus groups were held with providers and patients at eight clinics. Results showed that providers' and patients' perceptions were similar. Participants were able to describe current care practices and identify two elements of best care: patient-focused care and access to care. However, both health care providers and patients acknowledged that financial constraints, appointment scheduling, and distance to clinics were some of the barriers to achieving best care. Case management and shared-care schemes are two strategies that are proposed to meet the challenge of providing collaborative integrated care that is accessible and equal to all, while still maintaining positive patient outcomes.

The nature of multidisciplinary HIV care in the ambulatory setting: a synthesis of the literature.

The purpose of this article is to provide a critical appraisal and synthesis of the literature relating to the provision of multidisciplinary HIV care in the ambulatory setting. As more people are living with HIV infection, and living longer, the demand for chronic care is great. Knowing what optimal care and treatment for people living with HIV/AIDS is and how to provide that care is an ongoing challenge. The literature suggests that the provision of care for HIV-infected individuals varies across and within HIV/AIDS clinics. This variability in care practices may influence the health and well-being of patients, and negatively impact on access to such care by people with HIV/AIDS. The goal of reviewing the literature on HIV-ambulatory clinics was to provide a description of a typical clinic, its staffing components, the care practices carried out at such a clinic (and by whom), and some barriers to providing optimal care. The ultimate goal of this review is to establish what is currently known about the provision of these services so that this information may build on existing knowledge and thereby standards of care for HIV-ambulatory clinics can be developed that could be implemented on a wide-scale basis.

Patient-focussed decision-making in early-stage prostate cancer: insights from a cognitively based decision aid.

PURPOSE: To study the cognitive processes of early-stage prostate cancer patients as they determined which treatment they preferred, using our cognitively based decision aid. METHOD: The aid was a one-to-one interview that included the structured presentation of information, listing exercises in which the patient identified attributes important to his decision, and trade-off exercises to help him weigh and integrate those attributes together. At various points of the interview, patients identified the attributes they felt were important to their decision, rated their treatment options and completed standardized assessments relating to their decision. In addition, patients participated in a follow-up interview at the time they made their actual treatment decision and again 3 months later. RESULTS: Sixty of 70 (86%) of the invited patients participated in the study. Participating patients identified a median of four important attributes (range 1-10); 36 different attributes were identified at some point in the interview by the group. During the interview, 78% of patients changed which attributes they considered important, and 72% changed their treatment ratings. Stability of treatment choice after the interview and lack of regret after the decision were each positively associated with increasing differentiation between treatment options over time. CONCLUSIONS: The decision process appears to be dynamic for the patients with great variability across patients in what is important to the decision. Increasing stability of choice and lack of regret appear to be related positively to increasing difference over time in how attractive the preferred option is over its closest competitor, rather than to the size of the difference at any one point in time.

Evaluation of a question-and-answer booklet on early-stage prostate-cancer.

A question-and-answer booklet about early-stage prostate-cancer was created for patients and their family members. Two sequential studies were conducted to determine if the single source of information would be useful to both patients and their families. The first study used 1:1 interviews with 11 readers (6 patients and 5 family members) to identify features of the booklet that may be problematic. In all, six features were identified as either irrelevant or problematic in their design. The second study was a survey of 54 patients (79% response rate) and 33 family members (49% response rate); the study was designed to obtain an overall evaluation of the booklet, to clarify the proportion of readers for whom the features identified in the first study were problematic, to provide insight into how and why readers were reading the booklet, and to determine if patients and family differed on any of the outcomes. Results showed that 85% of readers liked the booklet; most (81.6%) read it from beginning to end. Most readers in both groups wanted the information to help them understand (85.2% patients; 87.9% family); more patients than family wanted it for treatment decision making (44.4% patients; 27.3% family) and for planning (35.2% patients; 9.1% family); more family (42.4%) than patients (20.4%) wanted the information to help them provide support. We conclude that even though patients and family differ in why they want information, the booklet appears to be considered useful by both groups.