Understanding pharmacogenomic testing and its role in medicine prescribing

When making prescribing decisions, it is important for healthcare professionals to remember that individual patients may respond differently to medicines. For example, some patients may experience a therapeutic benefit while others may experience an adverse drug reaction. The aim of personalised medicine is to tailor treatment based not only on a patient's clinical factors, but also on their genetic profile. Pharmacogenomics is a branch of personalised medicine that is concerned with how differences in people's genomes affect their response to medicines. Pharmacogenomic testing, which recently has become less expensive and increasingly available, can inform nurses' prescribing decisions and improve patient outcomes. This article discusses personalised medicine and pharmacogenomics, including how pharmacogenomic testing can optimise medicine prescribing, and explains the role of nurses in the process

Persistent inequalities in Hospice at Home provision.

OBJECTIVE: To describe the nature and scope of a new Hospice at Home (H@H) service and to identify its equality of provision. METHODS: Case note review of patients supported by a H@H service for 1 year from September 2012 to August 2013 (n=321). Descriptive analysis to report frequencies and proportions of quantitative data extracted from service logs, referral forms and care records; thematic analysis of qualitative data from care record free text. RESULTS: Demand outstripped supply. Twice as many night care episodes were requested (n=1237) as were provided (n=613). Inequalities in access to the service related to underlying diagnosis and socioeconomic status. 75% of patients using the service had cancer (221/293 with documented diagnosis). Of those who died at home in the areas surrounding the hospice, 53% (163/311) of people with cancer and 11% (49/431) of those without cancer received H@H support. People who received H@H care were often more affluent than the population average for the area within which they lived. Roles of the service identified included: care planning/implementation, specialist end-of-life care assessment and advice, 'holding' complex patients until hospice beds become available and clinical nursing care. CONCLUSION: There is significant unmet need and potentially large latent demand for the H@H service. People without cancer or of lower socioeconomic status are less likely to access the service. Action is needed to ensure greater and more equitable service provision in this and similar services nationally and internationally

When Frail Older People Relocate in Very Old Age, Who Makes the Decision?

Older people are likely to transition to a new home closer to family who can provide assistance or to long-term residential care as their health declines and their care needs increase. A minority choose to move to "age-friendly" housing before the onset of disability, but the majority prefer to "age in place" and defer moving until health crises compel a transition. Older people living with dementia are likely to move into residential care, but not much is known about the role they play in decision making around these moves. This qualitative study addresses this gap in knowledge by examining how a rare cohort of "older old" people, most with some level of cognitive impairment, were involved in decisions surrounding assistance seeking and moving to a care home. Thematic analysis of qualitative interview data from Cambridge City over-75s Cohort (CC75C) study participants aged 95 years and older, who had moved in later life, and their proxy informants (n = 26). Moves at such an old age were made due to a complexity of push and pull factors which had layered dynamics of decision making. In most cases (n = 22), decision making involved other people with varying degrees of decision ownership. Only four older people, who moved voluntarily, had full ownership of the decision to move. Many relatives reported being traumatized by events leading up to the move. "Older old" people are sometimes unable to make their own decisions about moving due to the urgency of health crisis and cognitive decline. There is a need to support relatives to discuss moving and housing options at timely junctures before health crises intervene in an effort to optimize older people's participation in decision making

The collection and reporting of measures of deprivation in musculoskeletal research: an international survey study

Background: The reporting of deprivation measures is typically poor in musculoskeletal (MSK) research. Aims: To explore MSK researcher's perspectives on the deprivation indices and measures that are, or could be, collected and reported in their studies, and potential barriers and facilitators to collecting these data. Materials & Methods: An online international survey was undertaken to determine knowledge, use and reporting of deprivation indices and measures by MSK researchers and the factors which influence this. Data were analysed using descriptive statistics. Results: 42 respondents from 16 countries completed the survey. The index of multiple deprivation was the most well-known measure (26%) although only 17% had reported data from this index. Most commonly reported markers of deprivation were: employment (60%), education (60%) and ethnicity (50%). Most common barriers to collecting these data included: uncertainty on perceived importance of deprivation measures (79%), what should be collected (71%), and concerns on missing data and sensitivities from participants reluctant to provide this information (33%). Consensus on necessary measures to be collected and reported (88%) and improved awareness of the relationship between deprivation and MSK health (79%) were considered key activities to improve deprivation recording in MSK research. Discussion & Conclusion: There is poor awareness of the collection and reporting of deprivation measures in MSK research. Greater understanding on the importance of these data in reducing inequalities in MSK care is needed to facilitate improvement. This would enable greater assessment of generalisability and to assess whether interventions have different effects in people from different socio-economic groups

Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation

OBJECTIVE: To assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England. METHODS: Data on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011-June 2014 and July 2014-December 2017. RESULTS: Between 2011-2014 and 2014-2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI -11.5% to -11.1%) from 86 467 in 2011-2014 to 76 730 in 2014-2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289. CONCLUSIONS: Despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level

Bridging the impactibility gap in population health management: a systematic review

Objectives Assess whether impactibility modelling is being used to refine risk stratification for preventive health interventions. Design Systematic review. Setting Primary and secondary healthcare populations. Papers Articles published from 2010 to 2020 on the use or implementation of impactibility modelling in population health management, reported with the terms a € intervenability', a € amenability', and a € propensity to succeed' (PTS) and associated with the themes a € care sensitivity', a € characteristic responders', a € needs gap', a € case finding', a € patient selection' and a € risk stratification'. Interventions Qualitative synthesis to identify themes for approaches to impactibility modelling. Results Of 1244 records identified, 20 were eligible for inclusion. Identified themes were a € health conditions amenable to care' (n=6), a € PTS modelling' (n=8) and a € comparison or combination with clinical judgement' (n=6). For the theme a € health conditions amenable to care', changes in practice did not reduce admissions, particularly for ambulatory care sensitive conditions, and sometimes increased them, with implementation noted as a possible issue. For a € PTS modelling', high costs and needs did not necessarily equate to high impactibility and targeting a larger number of individuals with disorders associated with lower costs had more potential. PTS modelling seemed to improve accuracy in care planning, estimation of cost savings, engagement and/or care quality. The a € comparison or combination with clinical judgement' theme suggested that models can reach reasonable to good discriminatory power to detect impactable patients. For instance, a model used to identify patients appropriate for proactive multimorbid care management showed good concordance with physicians (c-statistic 0.75). Another model employing electronic health record scores reached 65% concordance with nurse and physician decisions when referring elderly hospitalised patients to a readmission prevention programme. However, healthcare professionals consider much wider information that might improve or impede the likelihood of treatment impact, suggesting that complementary use of models might be optimum. Conclusions The efficiency and equity of targeted preventive care guided by risk stratification could be augmented and personalised by impactibility modelling

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish Renal Registry

BackgroundInfection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland.MethodsStudy design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed.Results During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. ConclusionThe rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection. <br/

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation