Objective
Decision‐making capacity assessments for hospital settings are challenging as it is dominated by the ethical and legal principles of maintaining autonomy and protection. Health clinicians, ...especially in rural areas, are challenged with a lack of a standardised processes and pathways for decision‐making capacity assessment. A literature review was conducted to determine what measurement tools clinicians are utilising in the hospital setting for decision‐making capacity assessment and how decisions relating to consent to treatment, independent living and finances are made.
Design
Literature review.
Method
A search of MEDLINE, EMBASE and PsycINFO databases from January 2006 to April 2019 was conducted for peer‐reviewed articles to determine how decision‐making capacity assessments are conducted and the tools clinicians are utilising in the hospital setting.
Results
Five main themes were identified from this review: (a) domains of capacity; (b) capacity assessment; (c) capacity assessment instruments; (d) who performs capacity assessment; and (e) challenges and limitations to capacity assessment in the hospital setting. Currently, there is no gold standard for capacity assessment.
Conclusion
This review shows that there is currently a lack of a uniform approach or a singular test to determine capacity. It is proposed that a multidisciplinary approach to decision‐making capacity assessment could be an effective model in the hospital setting, especially in rural health due to limited access to aged care specialists. It is important that clinicians receive ongoing training in decision‐making capacity assessment and further research is recommended in this specialised area of practice.
Hypertrophic cardiomyopathy (HCM) exhibits genetic heterogeneity that is dominated by variation in eight sarcomeric genes. Genetic variation in a large number of non-sarcomeric genes has also been ...implicated in HCM but not formally assessed. Here we used very large case and control cohorts to determine the extent to which variation in non-sarcomeric genes contributes to HCM.
We sequenced known and putative HCM genes in a new large prospective HCM cohort (n = 804) and analysed data alongside the largest published series of clinically genotyped HCM patients (n = 6179), previously published HCM cohorts and reference population samples from the exome aggregation consortium (ExAC, n = 60 706) to assess variation in 31 genes implicated in HCM. We found no significant excess of rare (minor allele frequency < 1:10 000 in ExAC) protein-altering variants over controls for most genes tested and conclude that novel variants in these genes are rarely interpretable, even for genes with previous evidence of co-segregation (e.g. ACTN2). To provide an aid for variant interpretation, we integrated HCM gene sequence data with aggregated pedigree and functional data and suggest a means of assessing gene pathogenicity in HCM using this evidence.
We show that genetic variation in the majority of non-sarcomeric genes implicated in HCM is not associated with the condition, reinforce the fact that the sarcomeric gene variation is the primary cause of HCM known to date and underscore that the aetiology of HCM is unknown in the majority of patients.
Objective
Clinicians are challenged to decide when and how to conduct decision‐making capacity assessment and guardianship applications for confused hospitalised older patients. This study aimed to ...understand the characteristics of confused hospitalised older patients who require decision‐making capacity assessment and guardianship applications and to determine the impact of a locally introduced capacity testing procedure on the conduct of decision‐making capacity assessment and guardianship application in a regional hospital setting.
Design
Before and after study.
Setting
Regional New South Wales hospital.
Participants
Twenty‐four confused hospitalised older patients who had decision‐making capacity assessment during November 2014‐April 2015 and November 2015‐April 2016.
Main outcome measure
The impact of a standardised capacity testing procedure on the conduct of decision‐making capacity assessment.
Results
After capacity testing procedure implementation, there were significant improvements in the number of multidisciplinary team meetings, documentation of decision‐making capacity assessment process and length of stay. The majority of patients who required guardianship application was aged over 70 years, had a medical history of dementia, >20 days of acute hospital admission and had no evidence of future care‐planning.
Conclusion
Implementation of capacity testing procedure is likely to have contributed to the positive changes in the conduct of decision‐making capacity assessment and guardianship application process for confused hospitalised older patients. This study provides some evidence of decision‐making capacity assessment process gaps; and indicates clinical and demographic characteristics of confused hospitalised older patients who might require decision‐making capacity assessment and guardianship applications. The evidence of lack of appropriate future care‐planning for ageing patients and increasing hospital admissions of confused hospitalised older patients presents future challenges in rural health.
The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated ...cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.
In India, there are many kinds of atrocities against transpeople that have ensued in the country over the past decades. The legal system has failed them. Most people do not even go to the police ...because they havbe so often been told that they deserve such treatment.
Molecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced ...high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.
We evaluated two next-generation sequencing (NGS) platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm), and sequenced on the MiSeq (Illumina) and Ion Torrent PGM (Life Technologies). Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%). At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs), with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.
MiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias, these NGS approaches are faster, less expensive, and yet more comprehensive.
Home visitation has emerged as an effective model to provide high-quality care during pregnancy, childbirth, and post-natal period and improve the health outcomes of mother- new born dyad. This 360
...assessment documented the constraints faced by the community health workers (known as the Accredited Social Health Activists, ASHAs) to accomplish home visitation and deliver quality services in a poor-performing district and co-created the strategies to overcome these using a nexus planning approach.
The study was conducted in the Raisen district of Madhya Pradesh, India. The grounded theory approach was applied for data collection and analysis using in-depth interviews, and focus group discussions with stakeholders representing from health system (including the ASHAs) and the community (rural population). A key group of diverse stakeholders were convened to utilize the nexus planning five domain framework (social-cultural, educational, organizational, economic, and physical) to prioritize the challenges and co-create solutions for improving the home visitation program performance and quality. The nexus framework provides a systemic lens for evaluating the success of the ASHAs home visitation program.
The societal (caste and economic discrimination), and personal (domestic responsibilities and cultural constraints of working in the village milieu) issues emerged as the key constraints for completing home visits. The programmatic gaps in imparting technical knowledge and skills, mentoring system, communication abilities, and unsatisfactory remuneration system were the other barriers to the credibility of the services. The nexus planning framework emphasized that each of the above factors/domains is intertwined and affects or depends on each other for home-based maternal and newborn care services delivered with quality through the ASHAs.
The home visitation program services, quality and impact can be enhanced by addressing the social-cultural, organizational, educational, economic, and physical nexus domains with concurrent efforts for skill and confidence enhancement of the ASHAs and their credibility.
We aimed to determine the mutation yield and clinical applicability of "molecular autopsy" following sudden arrhythmic death syndrome (SADS) by validating and utilizing low-cost high-throughput ...technologies: Fluidigm Access Array PCR-enrichment with Illumina HiSeq 2000 next generation sequencing (NGS).
We validated and optimized the NGS platform with a subset of 46 patients by comparison with Sanger sequencing of coding exons of major arrhythmia risk-genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2). A combined large multi-ethnic international SADS cohort was sequenced utilizing the NGS platform to determine overall molecular yield; rare variants identified by NGS were subsequently reconfirmed by Sanger sequencing.
The NGS platform demonstrated 100% sensitivity for pathogenic variants as well as 87.20% sensitivity and 99.99% specificity for all substitutions (optimization subset, n = 46). The positive predictive value (PPV) for NGS for rare substitutions was 16.0% (27 confirmed rare variants of 169 positive NGS calls in 151 additional cases). The overall molecular yield in 197 multi-ethnic SADS cases (mean age 22.6 ± 14.4 years, 68% male) was 5.1% (95% confidence interval 2.0-8.1%), representing 10 cases carrying pathogenic or likely pathogenic risk-mutations.
Molecular autopsy with Fluidigm Access Array and Illumina HiSeq NGS utilizing a selected panel of LQTS/BrS and CPVT risk-genes offers moderate diagnostic yield, albeit requiring confirmatory Sanger-sequencing of mutational variants.
Inflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in ...premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score=1.114, p=0.011 in linkage analysis; pi=0.55, p=0.008 in identity by descent; LOD score=1.06, p=0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p=0.0017, 95% confidence interval CI: 1.68-8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p<0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.
NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there ...have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/Sanger versus targeted NGS.
In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC) followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC). The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy.
NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits). There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150) to 31.3% (47/150).
Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%). None of the homozygous samples were detected by dHPLC analysis.
NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised population.
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