Economic evaluation of a group-based exercise program for falls prevention among the older community-dwelling population

BACKGROUND: Falls among older people are of growing concern globally. Implementing cost-effective strategies for their prevention is of utmost importance given the ageing population and associated potential for increased costs of fall-related injury over the next decades. The purpose of this study was to undertake a cost-utility analysis and secondary cost-effectiveness analysis from a healthcare system perspective, of a group-based exercise program compared to routine care for falls prevention in an older community-dwelling population. METHODS: A decision analysis using a decision tree model was based on the results of a previously published randomised controlled trial with a community-dwelling population aged over 70. Measures of falls, fall-related injuries and resource use were directly obtained from trial data and supplemented by literature-based utility measures. A sub-group analysis was performed of women only. Cost estimates are reported in 2010 British Pound Sterling (GBP). RESULTS: The ICER of GBP£51,483 per QALY for the base case analysis was well above the accepted cost-effectiveness threshold of GBP£20,000 to £30,000 per QALY, but in a sensitivity analysis with minimised program implementation the incremental cost reached GBP£25,678 per QALY. The ICER value at 95% confidence in the base case analysis was GBP£99,664 per QALY and GBP£50,549 per QALY in the lower cost analysis. Males had a 44% lower injury rate if they fell, compared to females resulting in a more favourable ICER for the women only analysis. For women only the ICER was GBP£22,986 per QALY in the base case and was below the cost-effectiveness threshold for all other variations of program implementation. The ICER value at 95% confidence was GBP£48,212 in the women only base case analysis and GBP£23,645 in the lower cost analysis. The base case incremental cost per fall averted was GBP£652 (GBP£616 for women only). A threshold analysis indicates that this exercise program cannot realistically break even. CONCLUSIONS: The results suggest that this exercise program is cost-effective for women only. There is no evidence to support its cost-effectiveness in a group of mixed gender unless the costs of program implementation are minimal. Conservative assumptions may have underestimated the true cost-effectiveness of the program

A Rare Coincidence of Two Coronary Anomalies in an Adult

Anomalous right-sided left main coronary arteries and dual type IV left anterior descending arteries are rare coronary anomalies. In this case report, we present a 59 year old man with atypical chest pain and a combination of the above coronary anomalies as identified by selective coronary angiography and computed tomography angiography. To the best of our knowledge, the coincidence of these coronary anomalies has not been previously described

Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells

Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments.United States. National Institutes of Health (DE-013023)United States. National Institutes of Health (DC-007174)United States. National Institutes of Health (DC-013909)United States. National Institutes of Health (RR-00168

Pharmacogenomics is the future of prescribing inpsychiatry

NoPatients' pharmacogenetic data could be used to improve adherence to antipsychotic medication by increasing the likelihood of therapeutic response and reducing the prevalence of adverse drug reactions

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

What Are the Barriers and Enablers to the Implementation of Pharmacogenetic Testing in Mental Health Care Settings?

In psychiatry, the selection of antipsychotics and antidepressants is generally led by a trial-and-error approach. The prescribing of these medications is complicated by sub-optimal efficacy and high rates of adverse drug reactions (ADRs). These both contribute to poor levels of adherence. Pharmacogenetics (PGx) considers how genetic variation can influence an individual’s response to a drug. Pharmacogenetic testing is a tool that could aid clinicians when selecting psychotropic medications, as part of a more personalized approach to prescribing. This may improve the use of and adherence to these medications. Yet to date, the implementation of PGx in mental health environments in the United Kingdom has been slow. This review aims to identify the current barriers and enablers to the implementation of PGx in psychiatry and determine how this can be applied to the uptake of PGx by NHS mental health providers. A systematic searching strategy was developed, and searches were carried out on the PsychInfo, EmBase, and PubMed databases, yielding 11 appropriate papers. Common barriers to the implementation of PGx included cost, concerns over incorporation into current workflow and a lack of knowledge about PGx; whilst frequent enablers included optimism that PGx could lead to precision medicine, reduce ADRs and become a more routine part of psychiatric clinical care. The uptake of PGx in psychiatric care settings in the NHS should consider and overcome these barriers, while looking to capitalize on the enablers identified in this review

Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study

Background:: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual’s genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose of psychosis drugs to an individual’s genetics, particularly psychosis drugs with known variable response due to CYP2D6 gene variants (‘CYP2D6-PGx antipsychotics’). Aims:: This study aims to investigate differences between demographic groups prescribed ‘CYP2D6-PGx antipsychotics’ and estimate the proportion of patients eligible for PGx testing based on current pharmacogenomics guidance. Methods:: A cross-sectional study took place extracting data from 243 patients’ medical records to explore psychosis drug prescribing, including drug transitions. Demographic data such as age, sex, ethnicity, and clinical sub-team were collected and summarised. Descriptive statistics explored the proportion of ‘CYP2D6-PGx antipsychotic’ prescribing and the nature of transitions. We used logistic regression analysis to investigate associations between demographic variables and prescription of ‘CYP2D6-PGx antipsychotic’ versus ‘non-CYP2D6-PGx antipsychotic’. Results:: Two-thirds (164) of patients had been prescribed a ‘CYP2D6-PGx antipsychotic’ (aripiprazole, risperidone, haloperidol or zuclopenthixol). Over a fifth (23%) of patients would have met the suggested criteria for PGx testing, following two psychosis drug trials. There were no statistically significant differences between age, sex, or ethnicity in the likelihood of being prescribed a ‘CYP2D6-PGx antipsychotic’. Conclusions:: This study demonstrated high rates of prescribing ‘CYP2D6-PGx-antipsychotics’ in an EIP cohort, providing a rationale for further exploration of how PGx testing can be implemented in EIP services to personalise the prescribing of drugs for psychosis

Associations between exemption and survival outcomes in the UK's primary care pay-for-performance programme:a retrospective cohort study

PublishedJournal ArticleThis is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVES: The UK's Quality and Outcomes Framework permits practices to exempt patients from financially-incentivised performance targets. To better understand the determinants and consequences of being exempted from the framework, we investigated the associations between exception reporting, patient characteristics and mortality. We also quantified the proportion of exempted patients that met quality targets for a tracer condition (diabetes). DESIGN: Retrospective longitudinal study, using individual patient data from the Clinical Practice Research Datalink. SETTING: 644 general practices, 2006/7 to 2011/12. PARTICIPANTS: Patients registered with study practices for at least one year over the study period, with at least one condition of interest (2 460 341 in total). MAIN OUTCOME MEASURES: Exception reporting rates by reason (clinical contraindication, patient dissent); all-cause mortality in year following exemption. Analyses with logistic and Cox proportional-hazards regressions, respectively. RESULTS: The odds of being exempted increased with age, deprivation and multimorbidity. Men were more likely to be exempted but this was largely attributable to higher prevalence of conditions with high exemption rates. Modest associations remained, with women more likely to be exempted due to clinical contraindication (OR 0.90, 99% CI 0.88 to 0.92) and men more likely to be exempted due to informed dissent (OR 1.08, 99% CI 1.06 to 1.10). More deprived areas (both for practice location and patient residence) were non-linearly associated with higher exception rates, after controlling for comorbidities and other covariates, with stronger associations for clinical contraindication. Compared with patients with a single condition, odds ratios for patients with two, three, or four or more conditions were respectively 4.28 (99% CI 4.18 to 4.38), 16.32 (99% CI 15.82 to 16.83) and 68.69 (99% CI 66.12 to 71.37) for contraindication, and 2.68 (99% CI 2.63 to 2.74), 4.02 (99% CI 3.91 to 4.13) and 5.17 (99% CI 5.00 to 5.35) for informed dissent. Exempted patients had a higher adjusted risk of death in the following year than non-exempted patients, regardless of whether this exemption was for contraindication (hazard ratio 1.37, 99% CI 1.33 to 1.40) or for informed dissent (1.20, 99% CI 1.17 to 1.24). On average, quality standards were met for 48% of exempted patients in the diabetes domain, but there was wide variation across indicators (ranging from 8 to 80%). CONCLUSIONS: Older, multimorbid and more deprived patients are more likely to be exempted from the scheme. Exception reported patients are more likely to die in the following year, whether they are exempted by the practice for a contraindication or by themselves through informed dissent. Further research is needed to understand the relationship between exception reporting and patient outcomes.NIHR School for Primary Care Research (Project #141); Medical Research Council; Health eResearch Centre grant MR/K006665/1

Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model

Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes. However, the cell signaling networks in mature, non-cutaneous neurofibromas remain unexplored. Here, we present insights into the cellular composition and signaling within mature neurofibromas, contrasting with normal adjacent tissue, in a porcine model of NF1 using single-cell RNA sequencing (scRNA-seq) analysis and histopathological characterization. These neurofibromas exhibited classic diffuse-type histologic morphology and expected patterns of S100, SOX10, GFAP, and CD34 immunohistochemistry. The porcine mature neurofibromas closely resemble human neurofibromas histologically and contain all known cellular components of their human counterparts. The scRNA-seq confirmed the presence of all expected cell types within these neurofibromas and identified novel populations of fibroblasts and immune cells, which may contribute to the tumor microenvironment by suppressing inflammation, promoting M2 macrophage polarization, increasing fibrosis, and driving the proliferation of Schwann cells. Notably, we identified tumor-associated IDO1+/CD274+ (PD-L1)+ dendritic cells, which represent the first such observation in any NF1 animal model and suggest the role of the upregulation of immune checkpoints in mature neurofibromas. Finally, we observed that cell types in the tumor microenvironment are poised to promote immune evasion, extracellular matrix reconstruction, and nerve regeneration