Review of available national guidelines for obstetric anal sphincter injury.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIs) are the most severe form of perineal trauma with potentially devastating effects on a mother's quality of life. There are various national guidelines available for their management. The aim of this study was to review and compare recommendations from published national guidelines regarding management and prevention of OASI. METHODS: We searched the PUBMED, EMBASE, MEDLINE, CINAHL and COCHRANE databases from January 2008 till October 2019 using relevant Medical Subject Headings (MeSH), including all subheadings. The guideline characteristics were mapped and methodological quality assessed with the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool by three independent reviewers. To compare the methodological quality of the guidelines, the interpretation of the six domain scores were taken into consideration. By consensus of the authors, a score of 70% was taken as a cut-off, and scores above this were considered 'high quality'. RESULTS: Thirteen national guidelines on perineal trauma were included and analysed. Nine of these were specific to OASI. There is wide variation in methodological quality and evidence used for recommendations. AGREE scores for overall guideline assessment were > 70% in eight of the guidelines, with Australia-Queensland, Canada, the UK and USA scoring highest. CONCLUSIONS: The wide variation in methodological quality and evidence used for recommendations suggests that there is a need for an agreed international guideline. This will enable healthcare practitioners to follow the same recommendations, with the most recent evidence, and provide evidence-based care to all women globally

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited