Endometriosis is a common complex inflammatory condition characterised by the presence of endometrium-like tissue outside the uterus, mainly in the pelvic area. It is associated with chronic pelvic pain and infertility, and its pathogenesis remains poorly understood. The disease is typically classified according to the revised American Fertility Society (rAFS) 4-stage surgical assessment system, although stage does not correlate well with symptomatology or prognosis. Previously identified genetic variants mainly are associated with stage III/IV disease, highlighting the need for further phenotype-stratified analysis that requires larger datasets. We conducted a meta-analysis of 15 genome-wide association studies (GWAS) and a replication analysis, including 58,115 cases and 733,480 controls in total, and sub-phenotype analyses of stage I/II, stage III/IV and infertility-associated endometriosis cases. This revealed 27 genetic loci associated with endometriosis at the genome-wide p-value threshold (P<5×10−8), 13 of which are novel and an additional 8 novel genes identified from gene-based association analyses. Of the 27 loci, 21 (78%) had greater effect sizes in stage III/IV disease compared to stage I/II, 1 (4%) had greater effect size in stage I/II compared to stage III/IV and 17 (63%) had greater effect sizes when restricted to infertility-associated endometriosis cases compared to overall endometriosis. These results suggest that specific variants may confer risk for different sub-types of endometriosis through distinct pathways. Analyses of genetic variants underlying different pain symptoms reported in the UK Biobank showed that 7/9 had positive significant (p<1.28×103) positive genetic correlations with endometriosis, suggesting a genetic basis for sensitivity to pain in general. Additional conditions with significant positive genetic correlations with endometriosis included uterine fibroids, excessive and irregular menstrual bleeding, osteoarthritis, diabetes as well as menstrual cycle length and age at menarche. These results provide a basis for fine-mapping of the causal variants at these 27 loci, and for functional follow-up to understand their contribution to endometriosis and its potential subtypes.
Prior experiences can lead patients with RA and comorbid anxiety and depression to feel they lack candidacy for care. Provision of equal priority to mental and physical health problems by GPs and improved continuity of care could help disclosure of mood concerns. Facilitation of access to psychological therapies could improve outcomes for both mental and physical health problems.
Background/Aims Osteoporosis is a burdensome disease internationally, that is commonly diagnosed following fragility fracture. In line with national guidance, in 2018 the North Staffordshire Fracture Liaison Service (FLS) changed their management policy of patients aged ≥85 years who sustain fragility fractures. Instead of calling these patients for a dual-energy X-ray absorptiometry (DXA) scan, a letter was sent to the patient’s General Practitioner, advising the empirical commencement of oral bisphosphonates. This audit aimed to evaluate whether the recommendations in this letter were enacted by GPs. Following audit, the text of the letter was changed, and a re-audit conducted to evaluate changes in practice. Methods Patients aged ≥85 years sustaining a fragility fracture between December 2018 and October 2020 were identified from FLS records. Summary Care Records (SCRs) were used to identify whether each patient was receiving a bisphosphonate prescription at time of audit (October 2020). Analysis was descriptive, to report the proportion of patients prescribed a bisphosphonate. Quality improvement methodology informed changes to the standard letter, using GP feedback. Re-audit of fragility fractures occurring between December 2020 and May 2021 was undertaken in July 2021 to assess possible impact. Results 408 eligible patients were identified in the initial audit, of which 79% were female. SCR data was available for 396 patients; median time between fracture and data collection was 9 months. 160 patients (40%) had a bisphosphonate prescribed as an acute or repeat prescription, of which >90% were alendronic acid. Following the first audit cycle, the letter was changed to address barriers to clinical decision-making including advice on relative contraindications and referral. 74 patient SCRs were reviewed in the 2nd audit cycle (85% female) and 38 (51%) were recorded as prescribed a bisphosphonate (median time between fracture and assessment 5-months). Conclusion Rates of bisphosphonate prescribing, in people aged ≥85 following a recommendation letter sent to the GP, have increased from 40% to 51% following quality improvement initiative. Furthermore, the proportion of patients prescribed a bisphosphonate is similar to previous national data in patients post-DXA. This is of interest, particularly given the de-prioritisation of non-communicable diseases during the COVID-19 pandemic, and demonstrates that an intervention which requires little time, can result in changes in practice. Limitations of this work include that the SCR only includes contemporaneous prescribing data so the period of time between drug recommendation and audit was different in 1st and 2nd cycles, meaning that adherence may be expected to be higher in the 2nd cycle, because the period of time between letter and data collection was shorter, and not because of a change in our intervention. Disclosure T. Appleyard: None. K. Bethwaite: None. N. Dale: None. F. Manning: None. Z. Paskins: None.
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