Comparing the Fiscal Consequences of Controlled and Uncontrolled Osteoarthritis Pain Applying a UK Public Economic Perspective

**Background:** Individuals experiencing osteoarthritis (OA) pain can pose significant costs for governments due to reduced work activity in these individuals and increasing reliance on public support benefits. In this analysis we capture the broader economic impact of OA pain by applying a government perspective, public economic framework to assess controlled and uncontrolled pain. **Methods:** We used a Markov model to compare labour market participation in people with uncontrolled OA hip or knee pain compared to a cohort with controlled OA pain. The likelihood of employment, long-term sickness, disability, and early retirement in those with controlled pain used publicly available UK data. The relative effect of uncontrolled OA pain on fiscal outcomes is drawn from peer reviewed publications reporting reduced work activity and reliance on public benefits for people with uncontrolled OA pain. Lost tax revenue was derived using UK tax rates and national insurance contributions applied to annual earnings. Social benefit rules were applied to calculate government financial support to individuals. Health-care costs were calculated based on estimates from an UK observational study. The base case analysis compared the projected lost tax revenue and transfer payments for a 50-year-old cohort with severe OA pain, retiring at age 65. **Results:** For a 50-year-old individual with moderate uncontrolled OA pain with 15-years remaining work expectancy, the model estimated a £62 383 reduction in employment earnings, a £24 307 reduction in tax contributions and a need for £16 034 in government benefits, compared to a person with controlled OA pain. In people with severe uncontrolled OA pain incremental foregone earnings were estimated to be £126 384, £44 925 were not paid through taxation and £25 829 were received in public benefits, compared to the controlled pain cohort. Health-care costs represented 13% and 12% of all OA-related fiscal cost in the moderate uncontrolled OA pain and severe uncontrolled OA pain comparison, respectively. **Conclusions:** For governments, maintaining an active workforce is paramount to maintaining economic growth and reducing spending on government programs. The approach described here can be used to augment cost-effectiveness models to inform a range of stakeholders of benefits attributed to controlled OA pain

A Deep 150 MHz GMRT Survey in Eridanus

We present results of a 150 MHz survey of a field centered on Epsilon Eridani, undertaken with the Giant Metrewave Radio Telescope (GMRT). The survey covers an area with a diameter of 2 deg, has a spatial resolution of 30" and a noise level of 3.1 mJy at the pointing centre. These observations provide a deeper and higher resolution view of the 150 MHz radio sky than the 7C survey (although the 7C survey covers a much larger area). A total of 113 sources were detected, most are point-like, but 20 are extended. We present an analysis of these sources, in conjunction with the NVSS (at 1.4 GHz) and VLSS (at 74 MHz). This process allowed us to identify 5 Ultra Steep Spectrum (USS) radio sources that are candidate high redshift radio galaxies (HzRGs). In addition, we have derived the dN/dS distribution for these observations and compare our results with other low frequency radio surveys.Comment: 12 pages, 11 figures, 3 tables, accepted for publication in MNRA

Celtic censure: representing Wales in eighteenth-century Germany

Drawing on Pierre Bourdieu's notion of regionalist discourse as the performative legitimation of specific frontiers, this article examines how the English traveller Samuel Jackson Pratt mediated a picture of the Welsh to late eighteenth-century readers in his Gleanings Through Wales, Holland and Westphalia (1795). This process of mediation was further complicated by the translation of this work into German as the Aehrenlese auf einer Reise durch Wallis, which appeared with the Leipzig publisher Lincke in 1798. While this work made an important contribution to German Celtophilia in the Romantic period, the German translator was careful to omit its more Sternean passages, in favour of factual narrative. Pratt's account of his travel through Wales, mediated in turn to a German audience through its Leipzig translator, therefore embodies several layers of cultural transfer that generate a complex and multifaceted image of Wales at the close of the eighteenth century

Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM. Methods: The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed. Results: Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34-57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic "red flags" were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences. Conclusion: ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism

YesCognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive deficits of relevance to schizophrenia in rodents and their subsequent reversal by first- and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-Choice Serial Reaction Time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of cognitive deficits and negative symptoms in schizophrenia

Prosodic Structure as a Parallel to Musical Structure

Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.What structural properties do language and music share? Although early speculation identified a wide variety of possibilities, the literature has largely focused on the parallels between musical structure and syntactic structure. Here, we argue that parallels between musical structure and prosodic structure deserve more attention. We review the evidence for a link between musical and prosodic structure and find it to be strong. In fact, certain elements of prosodic structure may provide a parsimonious comparison with musical structure without sacrificing empirical findings related to the parallels between language and music. We then develop several predictions related to such a hypothesis

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

The Hidden Economic Consequences of Migraine to the UK Government:Burden-of-Disease Analysis Using a Fiscal Framework

Background: Migraine is a highly prevalent and incapacitating neurological disorder associated with the highest global disability burden in people aged 15 to 49 years. Europe has the fourth-highest prevalence of migraine, after North America, South America, and Central America, and above Asia and Africa. Migraine leads to relatively modest direct healthcare expenditure but has substantial indirect costs due to reduced productivity. Methods: The economic burden of migraine was estimated in comparison with the general population of the United Kingdom (UK) using an analytical fiscal modeling framework applying the government cost perspective. Published measures of migraine's impact on labor participation were applied to rates of economic activity/inactivity of the general population. The model estimates lifetime changes to earnings from employment, direct and indirect taxes paid, and financial support requirements over the life course. Incremental differences between those affected and unaffected by migraine are reported as net fiscal consequences to public accounts. Fiscal costs are reported as the discounted average per capita over a 20-year time horizon and for the entire annual UK cohort with prevalent migraine. Results: People affected by migraine are more likely to be absent from work, unemployed, and disabled, and to retire early. A 44-year-old individual affected by migraine was associated with £19 823 in excess fiscal costs to the UK government, £1379 per year living with the condition, compared with someone not affected by the disease. Annually, migraine was estimated to represent £12.20 billion to the public economy, approximately £130.63 per migraine episode. The model predicted annual productivity losses in the health and social care workforce to be £2.05 billion and total annual productivity losses to be over £5.81 billion. Conclusions: This fiscal analysis monetizes the occupational consequences of migraine to the UK government, both in terms of lost tax revenue and transfer payments. The findings are substantial and useful to characterize disease severity and to inform the body of evidence considered by decision makers appraising the cost-effectiveness of health technologies.</p