Purpose:The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.Patients and methods:Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.Results:Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8% P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36% P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P=0.002).Conclusion:The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.

Objective To compare the survival rates of women with BRCA associated breast cancer who did and did not undergo mastectomy of the contralateral breast. Design Retrospective analysis.Setting 12 cancer genetics clinics.Participants 390 women with a family history of stage I or II breast cancer who were carriers of BRCA1 and BRCA2 mutations and initially treated with unilateral or bilateral mastectomy. 181 patients had mastectomy of the contralateral breast. Patients were followed for up to 20 years from diagnosis. Main outcome measure Death from breast cancer.Results 79 women died of breast cancer in the follow-up period (18 in the bilateral mastectomy group and 61 in the unilateral mastectomy group). The median follow-up time was 14.3 years (range 0.1-20.0 years). At 20 years the survival rate for women who had mastectomy of the contralateral breast was 88% (95% confidence interval 83% to 93%) and for those who did not was 66% (59% to 73%). In a multivariable analysis, controlling for age at diagnosis, year of diagnosis, treatment, and other prognostic features, contralateral mastectomy was associated with a 48% reduction in death from breast cancer (hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P=0.03). In a propensity score adjusted analysis of 79 matched pairs, the association was not significant (0.60, 0.34 to 1.06; P=0.08). Based on these results, we predict that of 100 women treated with contralateral mastectomy, 87 will be alive at 20 years compared with 66 of 100 women treated with unilateral mastectomy. ConclusionsThis study suggests that women who are positive for BRCA mutations and who are treated for stage I or II breast cancer with bilateral mastectomy are less likely to die from breast cancer than women who are treated with unilateral mastectomy. Given the small number of events in this cohort, further research is required to confirm these findings.

For women who carry a mutation in BRCA1 or BRCA2, the risk of breast cancer is up to 87% by the age of 70. There are options available to reduce the risk of breast cancer; however, each option has both risks and benefits, which makes decision making difficult. The objective is to develop and pilot test a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. The decision aid was developed and evaluated in three stages. In the first stage, the decision aid was developed and reviewed by cancer genetics experts. The second stage was a review of the decision aid by women with a BRCA1 or BRCA2 mutation for acceptability and feasibility. The final stage was a pre-test--post-test evaluation of the decision aid. Twenty-one women completed the pre-test questionnaire and 20 completed the post-test questionnaire. After using the decision aid, there was a significant decline in mean decisional conflict scores (p = 0.001), a significant improvement in knowledge scores (p = 0.004), and fewer women uncertain about prophylactic mastectomy (p = 0.003) and prophylactic oophorectomy (p = 0.009). Use of the decision aid decreased decisional conflict to levels suggestive of implementation of a decision. In addition, knowledge levels increased and choice predisposition changed with fewer women being uncertain about each option. This has significant clinical implications as it implies that with greater uptake of cancer prevention options by women with a BRCA1 or BRCA2 mutation, fewer women will develop and/or die of hereditary breast cancer.

Oophorectomy is associated with a decrease in mortality in women with breast cancer and a BRCA1 mutation. Women with estrogen receptor-negative breast cancer and a BRCA1 mutation should undergo oophorectomy shortly after diagnosis.

Background: Dysphagia occurs commonly in the intensive care unit (ICU). Despite the clinical relevance, there is little worldwide research on prevention, assessment, evaluation, and/or treatment of dysphagia for ICU patients. We aimed to gain insight into this international knowledge gap. Methods:We conducted a multi-center, international online cross-sectional survey of adult ICUs. Local survey distribution champions were recruited through professional and personal networks. The survey was administered from November 2017 to June 2019 with three email and a final telephone reminder. Results:Responses were received from 746 ICUs (26 countries). In patients intubated >48 hours, 17% expected a >50% chance that dysphagia would develop. This proportion increased to 43% in patients intubated >7 days, and to 52% in tracheotomized patients. Speech-language pathologist (SLP) consultation was available in 66% of ICUs, only 4% reported a dedicated SLP.Although 66% considered a routine post-extubation dysphagia protocol important, most (67%) did not have a protocol. Few ICUs routinely assessed for dysphagia after 48 hours intubation (30%) or tracheostomy (41%). A large proportion (46%) used water swallow screening tests to determine aspiration, few (8%) used instrumental assessments (i.e., flexible endoscopic evaluation of swallowing). Swallowing exercises were used for dysphagia management by 30% of ICUs.Conclusions: There seems to be limited awareness among ICU practioners that patients are at risk of dysphagia, particularly as ventilation persists, protocols, routine assessment and instrumental assessments are generally not used. We recommend the development of a research agenda to increase the quality of evidence and ameliorate the implementation of evidence-based dysphagia protocols by dedicated SLPs.

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Background: Patient decision aids (DA) supplement advice from health care professionals through provision of information on the likelihood of risks and benefits of treatment options. Ideally, these data are expressed in both visual and written form to communicate absolute risk or benefit (i.e., X/100). However, this well-accepted methodology lends itself to outcomes which are binary only. Valid methods for conversion of continuous outcomes for presentation in DAs are not well-established. The difficulty in converting these outcomes is compounded by the need to extract and pool aggregate standardized score data from multiple published sources to generate a single estimate of treatment effect. Our team was met with this challenge when developing a DA for refractory angina; the main outcome was angina frequency (AF) as measured by the AF subscale of the Seattle Angina Questionnaire. We aimed to develop and test the validity of a proposed method, based on statistical theory, for estimating absolute angina reduction based on AF scores. Methods: AF summary statistics, M(SD), were extracted from 2 distinct intervention studies for which raw data were accessible. A clinically important difference in AF scores was identified through expert consultation. Based on normal distribution theory, aggregate data from both studies were used to estimate the proportion of those who experienced a clinically significant change in AF. Chi-square comparisons of proportions was then used to determine if these estimates were dissimilar from true numbers reflected in the raw data. We then generated 500,000 simulated datasets using the same AF summary statistics, but with widely varying distribution characteristics (e.g., positive skew). Multiple comparisons of estimates to actual proportions of those experiencing a clinically significant change in AF were generated under simulated scenarios and expressed graphically. The effect of summary statistic on these comparisons was examined by conducting the simulations using both M(SD) and medians and interquartile ranges (IQR). Results: Overall agreement between estimated and actual proportions of those experiencing a clinically significant change in AF was excellent for the real study data; there were no significant differences (p >0.45), and no difference exceeded 5%. These results remained stable when data were pooled from the 2 studies using meta-analysis. For the simulated data sets, concordance between the estimated and actual proportions was also moderate to good in cases where data were not highly skewed (i.e. skewness <2.5); agreement improved in the context of medians and IQRs. Conclusion: Our results suggest that standard statistical theory can be used to estimate continuous outcomes in absolute terms with reasonable accuracy for use in DAs; caution is advised if outcomes are expected to be highly skewed in distribution.