A prospective cohort study measuring cost-benefit analysis of the Otago Exercise Programme in community dwelling adults with rheumatoid arthritis.

BACKGROUND: Falls are one of the major health problems in adults with Rheumatoid Arthritis (RA). Interventions, such as the Otago Exercise Programme (OEP), can reduce falls in community dwelling adults by up to 35%. The cost-benefits of such a programme in adults with RA have not been studied. The aims of this study were to determine the healthcare cost of falls in adults with RA, and estimate whether it may be cost efficient to roll out the OEP to improve function and prevent falls in adults living with RA. METHODS: Patients with Rheumatoid Arthritis aged ≥18 years were recruited from four rheumatology clinics across the Northwest of England. Participants were followed up for 1 year with monthly fall calendars, telephone calls and self-report questionnaires. Estimated medical cost of a fall-related injury incurred per-person were calculated and compared with OEP implementation costs to establish potential economic benefits. RESULTS: Five hundred thirty-five patients were recruited and 598 falls were reported by 195 patients. Cumulative medical costs resulting from all injury leading to hospital services is £374,354 (US$540,485). Average estimated cost per fall is £1120 (US$1617). Estimated cost of implementing the OEP for 535 people is £116,479 (US$168,504) or £217.72 (US$314.34) per-person. Based on effectiveness of the OEP it can be estimated that out of the 598 falls, 209 falls would be prevented. This suggests that £234,583 (US$338,116) savings could be made, a net benefit of £118,104 (US$170,623). CONCLUSIONS: Implementation of the OEP programme for patients with RA has potentially significant economic benefits and should be considered for patients with the condition

The relationship between well-being and commuting revisited: does the choice of methodology matter?

This paper provides an assessment of a range of alternative estimators for fixed-effects ordered models in the context of estimating the relationship between subjective well-being and commuting behaviour. In contrast to previous papers in the literature we find no evidence that longer commutes are associated with lower levels of subjective well-being, in general. From a methodological point of view our results support earlier findings that linear and ordered fixed-effects models of life satisfaction give similar results. However, we argue that ordered models are more appropriate as they are theoretically preferable, straightforward to implement and lead to easily interpretable results

The effectiveness and cost-effectiveness of strength and balance Exergames to reduce falls risk for people aged 55 years and older in UK assisted living facilities: A multi-centre, cluster randomised controlled trial

Background: Falls are the leading cause of fatal and non-fatal unintentional injuries in older people. The use of Exergames (active, gamified video-based exercises) is a possible innovative, community-based approach. This study aimed to determine the effectiveness of a tailored OTAGO/FaME based strength and balance Exergame programme for improving balance, maintaining function and reducing falls risk in older people. Methods: A two-arm cluster randomised controlled trial recruiting adults aged 55 years and older living in 18 assisted-living (sheltered housing) facilities (clusters) in the UK. Standard care (physiotherapy advice and leaflet) was compared to a tailored 12-week strength and balance Exergame programme, supported by physiotherapists or trained assistants. Complete-case analysis (intention to treat) was used to compare Berg Balance Scale (BBS) at baseline and at 12 weeks. Secondary outcomes included: fear of falling, mobility, falls risk, pain, mood, fatigue, cognition, healthcare utilisation and health-related quality of life; self-reported physical activity and falls. Results: Eighteen clusters were randomised (9 to each arm) with 56 participants allocated to the intervention and 50 to the control (78% female, mean age 78 years). Fourteen participants withdrew over the 12 weeks (both arms), mainly for ill health. There was an adjusted mean improvement in balance (BBS) of 6.2 (95% CI 2.4 to 10.0), reduced fear of falling (p=0.007) and pain (p=0.02) in Exergame group. Mean attendance at sessions was 69% (mean exercising time of 33 minutes/week). 24% of control group and 20% of Exergame group fell over trial period. The change in falls rates significantly favoured the intervention (incident rate ratio 0.31 (95% CI 0.16 to 0.62, p=0.001)). The point estimate of the incremental cost effectiveness ratio (ICER) was £15,209.80 per QALY. Using 10,000 bootstrap replications, at the lower bound of the NICE threshold of £20,000 per QALY, there was a 61% probability of Exergames being cost-effective, rising to 73% at the upper bound of £30,000 per QALY. Conclusions: Exergames, as delivered in this trial, improve balance, pain and fear of falling and are a cost-effective fall prevention strategy in assisted living facilities for people aged 55 years or older

Consultation patterns and frequent attenders in UK primary care from 2000 to 2019: A retrospective cohort analysis of consultation events across 845 general practices:a retrospective cohort analysis of consultation events across 845 general practices

OBJECTIVE: To describe the distribution of consultations at the practice level and examine whether increases are uniform or driven by people who consult more frequently. DESIGN: Retrospective cohort study. SETTING: UK general practice data from the Clinical Practice Research Datalink (CPRD) GOLD database. PARTICIPANTS: 1 699 709 314 consultation events from 12 330 545 patients, in 845 general practices (1 April 2000 to 31 March 2019). METHODS: Consultation information was aggregated by financial year into: all consultations/all staff; all consultations/general practitioners (GPs); face-to-face consultations/all staff; face-to-face consultations/GPs. Patients with a number of consultations above the 90th centile, within each year, were classified as frequent attenders. Negative binomial regressions examined the association between available practice characteristics and consultation distribution. RESULTS: Among frequent attenders, all consultations by GPs increased from a median (25th and 75th centile) of 13 (10 and 16) to 21 (18 and 25) and all consultations by all staff increased from 27 (23–30) to 60 (51–69) over the study period. Approximately four out of ten consultations of any type concerned frequent attenders and the proportion of consultations attributed to them increased over time, particularly for face-to-face consultations with GPs, from a median of 38.0% (35.9%–40.3%) in 2000–2001 to 43.0% (40.6%–46.4%) in 2018–2019. Regression analyses indicated decreasing trends over time for face-to-face consultations and increasing trends for all consultation types, for both GPs and all staff. Frequent attenders consulted approximately five times more than the rest of the practice population, on average, with adjusted incidence rate ratios ranging between 4.992 (95% CI 4.917 to 5.068) for face-to-face consultations with all staff and 5.603 (95% CI 5.560 to 5.647) for all consultations with GPs. CONCLUSIONS: Frequent attenders progressively contributed to increased workload in general practices across the UK from 2000 to 2019. Important knowledge gaps remain in terms of the demographic, social and health characteristics of frequent attenders and how UK general practices can be prepared to meet the needs of these patients

Risk of Falls and Fractures in Individuals With Cataract, Age-Related Macular Degeneration, or Glaucoma

IMPORTANCE: Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been implicated with falls and fracture risk, evidence is mixed, with the contribution of different eye diseases being uncertain.OBJECTIVE: To examine whether people with cataract, AMD, or glaucoma have higher risks of falls or fractures than those without.DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a population-based study in England using routinely collected electronic health records from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum primary care databases with linked hospitalization and mortality records from 2007 to 2020. Participants were people with cataract, AMD, or glaucoma matched to comparators (1:5) by age, sex, and general practice. Data were analyzed from May 2021 to June 2023.EXPOSURES: For each eye disease, we estimated the risk of falls or fractures using separate multivariable Cox proportional hazards regression models.MAIN OUTCOMES: Two primary outcomes were incident falls and incident fractures derived from general practice, hospital, and mortality records. Secondary outcomes were incident fractures of specific body sites.RESULTS: A total of 410 476 people with cataract, 75 622 with AMD, and 90 177 with glaucoma were matched (1:5) to 2 034 194 (no cataract), 375 548 (no AMD), and 448 179 (no glaucoma) comparators. The mean (SD) age was 73.8 (11.0) years, 79.4 (9.4) years, and 69.8 (13.1) years for participants with cataract, AMD, or glaucoma, respectively. Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma. Site-specific fracture analyses revealed increases in almost all body sites (including hip, spine, forearm, skull or facial bones, pelvis, ribs or sternum, and lower leg fractures) compared with matched comparators.CONCLUSIONS AND RELEVANCE: The results of this study support recognition that people with 1 or more of these eye diseases are at increased risk of both falls and fractures. They may benefit from improved advice, access, and referrals to falls prevention services.</p

A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity

The selectivity of an enzyme inhibitor is a key determinant of its usefulness as a tool compound or its safety as a drug. Yet selectivity is never assessed comprehensively in the early stages of the drug discovery process, and only rarely even in the later stages, because technical limitations prohibit doing otherwise. Here, we report EnPlex, an efficient, high-throughput method for simultaneously assessing inhibitor potency and specificity, and pilot its application to 96 serine hydrolases. EnPlex analysis of widely used serine hydrolase inhibitors revealed numerous previously unrecognized off-target interactions, some of which may help to explain previously confounding adverse effects. In addition, EnPlex screening of a hydrolase-directed library of boronic acid- and nitrile-containing compounds provided dual potency/selectivity structure-activity relationships from which lead candidates could be more effectively prioritized. Follow-up of a series of dipeptidyl peptidase 4 (DPP4) inhibitors showed that EnPlex indeed predicted efficacy and safety in animal models. These results demonstrate the feasibility and value of high-throughput, superfamily-wide selectivity profiling, and suggest such profiling can be incorporated into the earliest stages of drug discovery