A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people

Background: Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.Method: We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.Results: Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [ pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54-2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51-4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97-5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).Conclusion: LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon–intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations

Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer

Human epidermal growth factor receptor (HER)2 over-expression is associated with a shortened disease-free interval and poor survival. Although the addition of trastuzumab to chemotherapy in the first-line setting has improved response rates, progression-free survival, and overall survival, response rates declined when trastuzumab was used beyond the first-line setting because of multiple mechanisms of resistance. Studies have demonstrated the clinical utility of continuing trastuzumab beyond progression, and further trials to explore this concept are ongoing. New tyrosine kinase inhibitors, monoclonal antibodies, PTEN (phosphatase and tensin homolog) pathway regulators, HER2 antibody-drug conjugates, and inhibitors of heat shock protein-90 are being evaluated to determine whether they may have a role to play in treating trastuzumab-resistant metastatic breast cancer

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified