Risk for rheumatic disease in relation to ethnicity and admixture

Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease risk and to map the genes underlying these differences

Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review

The diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic 'dose-dependent' Type A reactions ii) 'idiosyncratic' or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/ toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.

Carpal tunnel syndrome associated with oral bisphosphonates. A population-based cohort study

© 2016 Carvajal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Bisphosphonates are widely used to prevent osteoporotic fractures. Some severe musculoskeletal reactions have been described with this medication; among them, some cases of carpal tunnel syndrome. Thus, the aim of this study was to explore whether bisphosphonates may be associated with this syndrome. Methods: A cohort study was conducted to compare exposed to unexposed women; the exposed group was that composed of women having received at least one prescription of an oral bisphosphonate. For the purpose, we used information from The Health Improvement Network (THIN) database. The outcome of interest was defined as those women diagnosed with carpal tunnel syndrome. A survival analysis was performed; the Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals, and to adjust for identified confounding variables. Results: Out of a sample of 59,475 women older than 51 years, 19,825 were treated with bisphosphonates during the period studied. No differences in age distribution or mean follow-up time were observed between the two groups in comparison. Overall, there were 572 women diagnosed with carpal tunnel syndrome, 242 (1.2%) in the group exposed to bisphosphonates, and 330 (0.8%) in the unexposed. An adjusted hazard ratio of developing carpal tunnel syndrome of 1.38 (95%CI, 1.15-1.64) was found for women exposed to bisphosphonates; no significant changes in the hazard ratios were found when considering different levels of bisphosphonate exposure

Improving reporting of adverse drug reactions: Systematic review

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, with many being identified post-marketing. Improvement in current ADR reporting, including utility of underused or innovative methods, is crucial to improve patient safety and public health. OBJECTIVES: To evaluate methods to improve ADR reporting via a systematic literature review. METHODS: Data sources were Medline, Embase, Cochrane Library and National Library for health searches on ADR reporting (January 1997 to August 2007) including cross-referenced articles. Twenty-four out of 260 eligible studies were identified and critically assessed. Studies were grouped as follows: i) spontaneous reporting (11); ii) medical chart/note review (2); iii) patient interviews/questionnaires (3); and iv) combination methods including computer-assisted methods (8). RESULTS: Using computerized monitoring systems (CMS) to generate signals associated with changes in laboratory results with other methods can improve ADR reporting. Educational interventions combined with reminders and/or prescription card reports can improve hospital-based ADR reporting, and showed short to medium term improvement. CONCLUSIONS: The use of electronic health data combined with other methods for ADR reporting can improve efficiency and accuracy for detecting ADRs and can be extended to other health care settings. Although methods with educational intervention appear to be effective, few studies have reviewed long-term effects to assess if the improvements can be sustained

Bisphosphonates and evidence for association with esophageal and gastric cancer:A systematic review and metaanalysis

OBJECTIVES: Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of epidemiological studies have been published with conflicting results. We conducted a systematic review and meta-analysis of observational studies, to determine the risk of esophageal and gastric cancer in users of bisphosphonates compared with non-users. DESIGN: We searched PubMed, MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating bisphosphonates and esophageal or gastric cancer. We calculated pooled ORs and 95% CIs for the risk of esophageal or gastric cancer in bisphosphonate users compared with non-users. We performed a sensitivity analysis of alendronate as this was the most common single drug studied and is also the most widely used in clinical practice. RESULTS: 11 studies (from 10 papers) examining bisphosphonate exposure and UGI cancer (gastric and esophageal), met our inclusion criteria. All studies were retrospective, 6/11 (55%) case–control and 5/11(45%) cohort, and carried out using data from 5 longitudinal clinical databases. Combining 5 studies (1 from each database), we found no increased risk, OR 1.11 (95% CI 0.97 to 1.27) of esophageal cancer in bisphosphonate users compared with non-users and no increased risk of gastric cancer in bisphosphonate users, OR 0.96 (95% CI 0.82 to 1.12). CONCLUSION: This is the fourth and most detailed meta-analysis on this topic. We have not identified any compelling evidence for a significantly raised risk of esophageal cancer or gastric cancer in male and female patients prescribed bisphosphonates

FCGR3B copy number variation is associated with systemic lupus erythematosus risk in Afro-Caribbeans.

OBJECTIVES: To evaluate FCGR3B copy number variation (CNV) in African and European populations and to determine if FCGR3B copy number is associated with SLE and SLE nephritis risk in Afro-Caribbeans, adjusting for African genetic ancestry. METHODS: We estimated FCGR3B to determine if there were ethnic variations in CNV (unrelated unadmixed Europeans and Africans). We then examined CNV at FCGR3B in relation to SLE and SLE nephritis within a case-control collection of 134 cases of SLE (37 with SLE nephritis) and 589 population controls of mainly Afro-Caribbean descent resident in Trinidad. RESULTS: We found a significant difference in copy number FCGR3B distribution between unadmixed African and European UK cohorts, with 27 (29%) vs 3 (5%) for those with low (0 or 1) copy FCGR3B, respectively, P = 0.002. In a Trinidadian SLE case-control study, low FCGR3B CNV was associated with SLE risk 1.7 (95% CI 1.1, 2.8), P = 0.02, which remained after adjustment for African genetic ancestry; odds ratios (ORs) 1.7 (95% CI 1.0, 2.8), P = 0.04. CONCLUSION: Our studies suggest that FCGR3B low copy number is associated with SLE risk in Afro-Caribbean populations independently of CNV due to African ancestry

Cross-sectional analysis of adverse outcomes in 1,029 pregnancies of Afro-Caribbean women in Trinidad with and without systemic lupus erythematosus

The objective of the study was to examine pregnancy outcomes in women with systemic lupus erythematosus (SLE) and population controls in Trinidad. We performed a cross-sectional analysis of adverse outcomes in pregnancies of Afro-Caribbean women with SLE and without SLE. One hundred and twenty-two female adult cases of SLE and 203 neighbourhood age-matched women without SLE were interviewed concerning details of their reproductive history, and the anticardiolipin antibody (ACL) status was established for women with SLE. A total of 1,029 pregnancies were reported (356 by women with SLE, 673 by women without SLE). In women with ≥ 1 pregnancy the total number of pregnancies was similar in women with a diagnosis of SLE and women without; however, a lower proportion of women with SLE had ever been pregnant compared with women without SLE (80% versus 91%, P = 0.002). In multivariate logistic regression analyses adjusted for maternal age, district of residence, pregnancy order and smoking, SLE pregnancies were more than twice as likely to end in foetal death than non-SLE pregnancies (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2–4.7). This effect was driven by a large increase in the odds of stillbirth (OR, 8.5; 95% CI, 2.5–28.8). The odds of early miscarriage (OR, 1.4; 95% CI, 0.6–3.1) and of mid-trimester miscarriage (OR, 1.9; 95% CI, 0.4–9.5) were higher, but were not statistically significantly different, in SLE pregnancies than in non-SLE pregnancies. The odds of ectopic pregnancy (OR, 7.5; 95% CI, 0.9–62.5) and of preterm birth (OR, 3.4; 95% CI, 1.2–10.0) were higher in SLE pregnancies conceived after diagnosis than in non-SLE pregnancies. There was no evidence of raised levels of IgG or IgM ACL among the majority (93/97 women, 96%) of SLE cases who reported sporadic mid-trimester miscarriage or stillbirth, although there was evidence of high levels of IgM and IgG ACL among women reporting three or more miscarriages and three consecutive miscarriages, and of raised IgG ACL among those experiencing ectopic pregnancy. In conclusion, we found evidence for a large increase in risk of stillbirth in the pregnancies of Afro-Caribbean Trinidadian women with SLE (not accounted for by high ACL status). There was some evidence of an increased risk of preterm delivery and ectopic pregnancy in pregnancies conceived after a diagnosis of maternal SLE

Risk of Covid-19 in shielded and nursing care home patients: cohort study in general practice

Background: Covid-19 cases were first detected in the UK in January 2020 and vulnerable patients were asked to shield from March to reduce their risk of Covid-19 infection. Aim: To determine the risk and determinants of Covid-19 diagnosis in shielded vs. non-shielded groups adjusted for key comorbidities not explained by shielding. Design: Retrospective cohort study of adults with COVID-19 infection between 1/2/20-15/5/20 in West London. Method: Individuals diagnosed with Covid-19 were identified in SystmOne records using clinical codes. Infection risks were adjusted for socio-demographic factors, nursing home status and comorbidities. Results: Of 57,713 adults, 573 (1%) individuals were identified as shielded and 1,074 adults had documented Covid-19 infections (1.9%). Covid-19 infection rate in the shielded group individuals compared with non-shielded adult individuals was 6.5 % (37/573) vs. 1.8 % (1,037/57, 140), p30kg/m2) 1.39 (1.18-1.63) p<0.001, and age 1.02 (1.01-1.02) p<0.001. Male gender was associated with lower risk of Covid-19 infection: 0.71 (0.62-0.82) p<0.001. Conclusion: Shielded individuals had a higher Covid-19 infection rate compared with non-shielded individuals, after adjusting for socio-demographic factors, nursing home status, and comorbidities