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

16 pagesPurpose 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

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

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials