The ability to preselect the donor genotype of iPSC lines provides important opportunities for immune matching in cell therapy. Here we propose that an international assessment should be made of how ...immune incompatibility can best be managed and how a network of GMP HLA homozygous haplobanks could be operated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
While a plethora of systematic reviews have provided evidence of efficacy, effectiveness and safety of direct‐acting oral anticoagulants (DOACs) in the management of nonvalvular atrial ...fibrillation, there has been little emphasis on clinicians' perspectives. This systematic review aimed to critically appraise, synthesize and present the available evidence of clinicians' views and experiences.
Methods
Studies published in English from January 2006 to July 2017 reporting the views and/or experiences of doctors, nurses or pharmacists on any individual DOAC or as a pharmacological group were included. Studies were assessed for quality by two researchers, data extracted and findings synthesized using a narrative approach.
Results
Following exclusion of duplicates, 777 titles, 394 s and 196 studies were screened. Ten studies were included in the review, nine of which were quantitative (cross‐sectional surveys) and one qualitative (semistructured interviews), with marked heterogeneity in outcomes reported. Studies were conducted exclusively in Europe and the USA. In those studies reporting clinician preference, DOACs were first choice over warfarin in naïve patients, based on perceptions of evidence of effectiveness equivalent or superior to warfarin and superior safety. Other advantageous factors were in those with an unstable International Normalized Ratio and likely to miss appointments. There were, however, concerns relating to management of over‐anticoagulation and experiences of observed bleeding rates.
Conclusion
There is a limited evidence base of clinicians' perspectives of DOACs, necessitating further research, particularly given the trajectory of increased use worldwide.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Following a diagnosis of cardiovascular disease there is a need for patients to self-manage. Health literacy has been shown to be lower in patients with cardiovascular disease, yet research into ...health literacy in this population is limited. This study used the Health Literacy Questionnaire (HLQ) to examine the health literacy and associated health, health behaviours and psychological profiles of cardiac rehabilitation patients from a remote and rural regional programme in the Scottish Highlands. Consecutive patients referred to the service in a calendar year were sent a cross-sectional questionnaire by post. Hierarchical cluster analysis grouped respondents based on their health literacy profile, and nonparametric methods were used to analyse differences between clusters on the other measures. A total of 282 participants responded (45.7%). Respondents were older (median: 71 years) and more likely to be from more affluent areas. Five health literacy clusters emerged with different profiles of health, physical activity, self-efficacy, motivation and illness perceptions. There was no difference in relation to cardiac rehabilitation attendance by health literacy cluster, but those with lower health literacy were less likely to be aware of the referral. Patterns of health literacy are associated with health, health behaviours and some psychological constructs. Knowledge of distinct cluster characteristics may help services better target interventions.
Genetic variation at classical HLA alleles influences many phenotypes, including susceptibility to autoimmune disease, resistance to pathogens and the risk of adverse drug reactions. However, ...classical HLA typing methods are often prohibitively expensive for large-scale studies. We previously described a method for imputing classical alleles from linked SNP genotype data. Here, we present a modification of the original algorithm implemented in a freely available software suite that combines local data preparation and QC with probabilistic imputation through a remote server.
We introduce two modifications to the original algorithm. First, we present a novel SNP selection function that leads to pronounced increases (up by 40% in some scenarios) in call rate. Second, we develop a parallelized model building algorithm that allows us to process a reference set of over 2500 individuals. In a validation experiment, we show that our framework produces highly accurate HLA type imputations at class I and class II loci for independent datasets: at call rates of 95-99%, imputation accuracy is between 92% and 98% at the four-digit level and over 97% at the two-digit level. We demonstrate utility of the method through analysis of a genome-wide association study for psoriasis where there is a known classical HLA risk allele (HLA-C*06:02). We show that the imputed allele shows stronger association with disease than any single SNP within the region. The imputation framework, HLA*IMP, provides a powerful tool for dissecting the architecture of genetic risk within the HLA.
HLA*IMP, implemented in C++ and Perl, is available from http://oxfordhla.well.ox.ac.uk and is free for academic use.
Statistical imputation of classical HLA alleles in case-control studies has become established as a valuable tool for identifying and fine-mapping signals of disease association in the MHC. ...Imputation into diverse populations has, however, remained challenging, mainly because of the additional haplotypic heterogeneity introduced by combining reference panels of different sources. We present an HLA type imputation model, HLA*IMP:02, designed to operate on a multi-population reference panel. HLA*IMP:02 is based on a graphical representation of haplotype structure. We present a probabilistic algorithm to build such models for the HLA region, accommodating genotyping error, haplotypic heterogeneity and the need for maximum accuracy at the HLA loci, generalizing the work of Browning and Browning (2007) and Ron et al. (1998). HLA*IMP:02 achieves an average 4-digit imputation accuracy on diverse European panels of 97% (call rate 97%). On non-European samples, 2-digit performance is over 90% for most loci and ethnicities where data available. HLA*IMP:02 supports imputation of HLA-DPB1 and HLA-DRB3-5, is highly tolerant of missing data in the imputation panel and works on standard genotype data from popular genotyping chips. It is publicly available in source code and as a user-friendly web service framework.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.
The aim of this study was to evaluate the impact of implementing a ...high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.
Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.
A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p < 0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).
Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome High-STEACS; NCT01852123).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genetic variation at classical HLA alleles is a crucial determinant of transplant success and susceptibility to a large number of infectious and autoimmune diseases. However, large-scale studies ...involving classical type I and type II HLA alleles might be limited by the cost of allele-typing technologies. Although recent studies have shown that some common HLA alleles can be tagged with small numbers of markers,
1,2
SNP-based tagging does not offer a complete solution to predicting HLA alleles. We have developed a new statistical methodology to use SNP variation within the region to predict alleles at key class I (
HLA-A,
HLA-B, and
HLA-C) and class II (
HLA-DRB1,
HLA-DQA1, and
HLA-DQB1) loci. Our results indicate that a single panel of ∼100 SNPs typed across the region is sufficient for predicting both rare and common HLA alleles with up to 95% accuracy in both African and non-African populations. Furthermore, we show that HLA alleles can be successfully predicted by using previously genotyped SNPs that are within the MHC and that had not been chosen for their ability to predict HLA alleles, such as those included on genome-wide products. These results indicate that our methodology, combined with an extended database of reference haplotypes, will facilitate large-scale experiments, including disease-association studies and vaccine trials, in which detailed information about HLA type is valuable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article is based on the address given by the author at the 2022 meeting of The American Society of Human Genetics (ASHG) in Los Angeles, California. The video of the original address can be ...found at the ASHG website.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiac rehabilitation (CR) has been shown to improve health behaviours and risk factors and the evidence suggests that home CR is as effective as hospital-based CR. Telemedicine offers the potential ...for more patients to engage in CR. We reviewed the evidence for patient focused Internet-based approaches to cardiovascular rehabilitation. Searches were performed in PubMed, EMBASE, Scopus and the Cochrane Controlled Trials Register. In total, nine studies involving 830 patients with heart disease that compared Internet-based cardiac rehabilitation to usual care were identified. The quality of trials was assessed using the Jadad scale. Outcome data were pooled under four subheadings: compliance; physical activity outcomes; clinical outcomes; psychosocial outcomes. Compliance rates were high but dropped over time in all studies. Physical activity measures were generally improved, as were clinical outcomes. Changes in psychosocial measures were positive, with two studies noting no change. No interventions noted a negative effect on outcomes. Despite the relatively small number of trials and the limited outcome measures, the results appeared to be positive with regard to patient outcomes and patient feedback. However, none had progressed to a clinical service.
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