A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non-hypertensive Alzheimer's patients

Introduction: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD. Methods: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients �65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. Results: We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]). Discussion: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.Scopu

Artificial Intelligence and Ethics in Dentistry: A Scoping Review

Dentistry increasingly integrates artificial intelligence (AI) to help improve the current state of clinical dental practice. However, this revolutionary technological field raises various complex ethical challenges. The objective of this systematic scoping review is to document the current uses of AI in dentistry and the ethical concerns or challenges they imply. Three health care databases (MEDLINE [PubMed], SciVerse Scopus, and Cochrane Library) and 2 computer science databases (ArXiv, IEEE Xplore) were searched. After identifying 1,553 records, the documents were filtered, and a full-text screening was performed. In total, 178 studies were retained and analyzed by 8 researchers specialized in dentistry, AI, and ethics. The team used Covidence for data extraction and Dedoose for the identification of ethics-related information. PRISMA guidelines were followed. Among the included studies, 130 (73.0%) studies were published after 2016, and 93 (52.2%) were published in journals specialized in computer sciences. The technologies used were neural learning techniques for 75 (42.1%), traditional learning techniques for 76 (42.7%), or a combination of several technologies for 20 (11.2%). Overall, 7 countries contributed to 109 (61.2%) studies. A total of 53 different applications of AI in dentistry were identified, involving most dental specialties. The use of initial data sets for internal validation was reported in 152 (85.4%) studies. Forty-five ethical issues (related to the use AI in dentistry) were reported in 22 (12.4%) studies around 6 principles: prudence (10 times), equity (8), privacy (8), responsibility (6), democratic participation (4), and solidarity (4). The ratio of studies mentioning AI-related ethical issues has remained similar in the past years, showing that there is no increasing interest in the field of dentistry on this topic. This study confirms the growing presence of AI in dentistry and highlights a current lack of information on the ethical challenges surrounding its use. In addition, the scarcity of studies sharing their code could prevent future replications. The authors formulate recommendations to contribute to a more responsible use of AI technologies in dentistry.Scopu

Development of a Checklist to Prevent Reconstructive Errors Made By Undergraduate Dental Students

Purpose: To design a checklist in order to reduce the frequency of reconstructive preventable errors (PE) performed by undergraduate dental students at McGill University. Materials and Methods: The most common PE occurring at a university dental clinic were identified by three reviewers analyzing the refunded cases, and used to create a preliminary checklist. This checklist was then validated by a panel of dental educators to produce a finalized 20-item checklist. The 20-question checklist was then submitted to students in a cross-sectional survey-based study to evaluate its relevance to undergraduate clinical education needs. Results: As many as 81% of students reported to have forgotten at least one item of the checklist during care of their last patient, and the most forgotten checklist items corresponded to the pretreatment stage. The students also reported that 17 of the 20 items in the checklist were relevant to a considerable extent or highly relevant. Conclusion: Common PE identified in the undergraduate clinic could be used to create a checklist of relevant items designed to reduce errors made by students and practitioners performing prosthodontic and reconstructive treatments. However, further studies are required to evaluate the implementation and efficiency of the checklist.Scopu