Matthew Franklin

Health status of UK care home residents: a cohort study

Background: UK care home residents are often poorly served by existing healthcare arrangements. Published descriptions of residents’ health status have been limited by lack of detail and use of data derived from surveys drawn from social, rather than health, care records. Aim: to describe in detail the health status and healthcare resource use of UK care home residents Design and setting: a 180-day longitudinal cohort study of 227 residents across 11 UK care homes, 5 nursing and 6 residential, selected to be representative for nursing/residential status and dementia registration. Method: Barthel index (BI), Mini-mental state examination (MMSE), Neuropsychiatric index (NPI), Mini-nutritional index (MNA), EuroQoL-5D (EQ-5D), 12-item General Health Questionnaire (GHQ-12), diagnoses and medications were recorded at baseline and BI, NPI, GHQ-12 and EQ-5D at follow-up after 180 days. National Health Service (NHS) resource use data were collected from databases of local healthcare providers. Results: out of a total of 323, 227 residents were recruited. The median BI was 9 (IQR: 2.5–15.5), MMSE 13 (4–22) and number of medications 8 (5.5–10.5). The mean number of diagnoses per resident was 6.2 (SD: 4). Thirty per cent were malnourished, 66% had evidence of behavioural disturbance. Residents had contact with the NHS on average once per month. Conclusion: residents from both residential and nursing settings are dependent, cognitively impaired, have mild frequent behavioural symptoms, multimorbidity, polypharmacy and frequently use NHS resources. Effective care for such a cohort requires broad expertise from multiple disciplines delivered in a co-ordinated and managed way.

The Identification of Seniors at Risk (ISAR) score to predict clinical outcomes and health service costs in older people discharged from UK acute medical units

Background: tools are required to identify high-risk older people in acute emergency settings so that appropriate services can be directed towards them. Objective: to evaluate whether the Identification of Seniors At Risk (ISAR) predicts the clinical outcomes and health and social services costs of older people discharged from acute medical units. Design: an observational cohort study using receiver–operator curve analysis to compare baseline ISAR to an adverse clinical outcome at 90 days (where an adverse outcome was any of death, institutionalisation, hospital readmission, increased dependency in activities of daily living (decrease of 2 or more points on the Barthel ADL Index), reduced mental well-being (increase of 2 or more points on the 12-point General Health Questionnaire) or reduced quality of life (reduction in the EuroQol-5D) and high health and social services costs over 90 days estimated from routine electronic service records. Setting: two acute medical units in the East Midlands, UK. Participants: a total of 667 patients aged ≥70 discharged from acute medical units. Results: an adverse outcome at 90 days was observed in 76% of participants. The ISAR was poor at predicting adverse outcomes (AUC: 0.60, 95% CI: 0.54–0.65) and fair for health and social care costs (AUC: 0.70, 95% CI: 0.59–0.81). Conclusions: adverse outcomes are common in older people discharged from acute medical units in the UK; the poor predictive ability of the ISAR in older people discharged from acute medical units makes it unsuitable as a sole tool in clinical decision-making.

Specialist geriatric medical assessment for patients discharged from hospital acute assessment units: randomised controlled trial.

Objective To evaluate the effect of specialist geriatric medical management on the outcomes of at risk older people discharged from acute medical assessment units. Design Individual patient randomised controlled trial comparing intervention with usual care. Setting Two hospitals in Nottingham and Leicester, UK. Participants 433 patients aged 70 or over who were discharged within 72 hours of attending an acute medical assessment unit and at risk of decline as indicated by a score of at least 2 on the Identification of Seniors At Risk tool. Intervention Assessment made on the acute medical assessment unit and further outpatient management by specialist physicians in geriatric medicine, including advice and support to primary care services. Main outcome measures The primary outcome was the number of days spent at home (for those admitted from home) or days spent in the same care home (if admitted from a care home) in the 90 days after randomisation. Secondary outcomes were determined at 90 days and included mortality, institutionalisation, dependency, mental wellbeing, quality of life, and health and social care resource use. Results The two groups were well matched for baseline characteristics, and withdrawal rates were similar in both groups (5%). Mean days at home over 90 days’ follow-up were 80.2 days in the control group and 79.7 in the intervention group. The 95% confidence interval for the difference in means was −4.6 to 3.6 days (P=0.31). No significant differences were found for any of the secondary outcomes. Conclusions This specialist geriatric medical intervention applied to an at risk population of older people attending and being discharged from acute medical units had no effect on patients’ outcomes or subsequent use of secondary care or long term care.

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention

BackgroundThe top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context.Methods/designA case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6–22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined.DiscussionThe health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.

Structural genomics for drug design against the pathogen Coxiella burnetii.

Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high‐throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure‐based drug design. This enzymes structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25‐fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. Proteins 2015; 83:2124–2136.

Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface.

Irreversible inhibition of the essential nervous system enzyme acetylcholinesterase by organophosphate nerve agents and pesticides may quickly lead to death. Oxime reactivators currently used as antidotes are generally less effective against pesticide exposure than nerve agent exposure, and pesticide exposure constitutes the majority of cases of organophosphate poisoning in the world. The current lack of published structural data specific to human acetylcholinesterase organophosphate‐inhibited and oxime‐bound states hinders development of effective medical treatments. We have solved structures of human acetylcholinesterase in different states in complex with the organophosphate insecticide, paraoxon, and oximes. Reaction with paraoxon results in a highly perturbed acyl loop that causes a narrowing of the gorge in the peripheral site that may impede entry of reactivators. This appears characteristic of acetylcholinesterase inhibition by organophosphate insecticides but not nerve agents. Additional changes seen at the dimer interface are novel and provide further examples of the disruptive effect of paraoxon. Ternary structures of paraoxon‐inhibited human acetylcholinesterase in complex with the oximes HI6 and 2‐PAM reveals relatively poor positioning for reactivation. This study provides a structural foundation for improved reactivator design for the treatment of organophosphate intoxication. Proteins 2016; 84:1246–1256.

The cost-effectiveness of antibiotic prophylaxis for patients at risk of infective endocarditis

Background: In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications. Methods: A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics. Results: AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 (

Rapid Countermeasure Discovery against Francisella tularensis Based on a Metabolic Network Reconstruction

26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million (

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS).

7.3–

PLEASANT: Preventing and Lessening Exacerbations of Asthma in School-age children Associated with a New Term - a cluster randomised controlled trial and economic evaluation

10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England. Conclusions: AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.