The Lancet Healthy Longevity

ImportanceEcological and observational studies have shown a protective association between herpes zoster (HZ) vaccination and dementia risk, yet many had methodological limitations or examined the live HZ vaccine that is no longer available in the US. Improved access to linked electronic health records for patients receiving post-acute care and long-term care permit robust comparisons of dementia risk in adults eligible to receive the recombinant HZ vaccine. ObjectiveEmulate a randomized trial in observational data to estimate the association of the recombinant HZ vaccine (RZV) with incident dementia risk among older adults newly admitted for post-acute or long-term care in nursing homes (NHs). DesignRetrospective cohort study with target trial emulation and the clone censor approach. SettingU.S. NHs that use PointClickCare as their electronic health record. ParticipantsIndividuals who were admitted to a NH between 01/01/2017-12/31/2022; Medicare fee-for-service beneficiaries; did not have prevalent dementia; and eligible to receive RZV as of admission. ExposuresReceive one or more RZV doses within one year of admission vs. do not receive any RZV over four years of follow-up. ResultsWe identified 509,926 eligible NH residents (mean age 79 years; 36% men). Among those alive, uncensored, and without dementia at 12 months of follow-up, 8,843 received one or more doses of RZV. Receipt of RZV within one year of NH admission was associated with a 5.8% lower absolute risk (95%CI: -3.9% to -7.5%) of newly diagnosed dementia over four years (risk ratio [RR] = 0.76 [95%CI: 0.69-0.84]; cumulative incidence in 1+ RZV vs. no RZV: 18.8% vs. 24.6%). Associations were smaller in men (RR=0.82 [95%CI: 0.68-1.01]) and those with prior live HZ vaccination (RR=0.86 [95%CI: 0.65-1.09]). Bias analyses based on two negative control outcomes (NCOs) attenuated, but did not fully explain, the main effect of RZV on dementia risk (bias-adjusted RR = 0.82 [wellness visit NCO] and RR = 0.88 [hip fracture NCO]). Conclusions and RelevanceAdministering RZV within 1 year of NH admission may reduce dementia risk. As RZV uptake was low overall, new NH residents would benefit from increased RZV vaccination uptake. KEY POINTSO_ST_ABSQuestionC_ST_ABSDoes the recombinant herpes zoster vaccine (RZV) reduce dementia risk among older adults? FindingsIn this cohort and trial emulation study of 509,926 patients newly admitted to skilled nursing or long-term care, we found that [≥]1 RZV dose within a year was associated with a 24% relative and 6% absolute reduction in 4-year dementia risk. Effects were robust to bias analyses and were stronger in women and those without prior vaccination with the live HZ vaccine. MeaningUsing causal inference methods, this observational study provides evidence that some cases of dementia may be prevented through vaccination with RZV.

BACKGROUNDAlzheimers disease and other dementias are progressive neurodegenerative disorders with profound impacts on cognitive function. There is a shortage of economic evidence relating to the impact Alzheimers disease on healthcare costs and quality-adjusted life-years (QALYs). METHODSWe employed two study designs to model the association between Alzheimers disease and healthcare costs and QALYs. We first estimated conventional multivariable models of the association between Alzheimers disease and these core economic outcomes. However, these types of model may be confounded by diseases, processes, or traits that independently affect Alzheimers disease and either or both of healthcare costs and QALYs. We therefore also explored a complementary approach using germline genetic variation as instrumental variables in a Mendelian randomization analysis. We used single nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies of Alzheimers disease as instruments. We studied outcome data on inpatient hospital costs and QALYs in the UK Biobank cohort. RESULTSData from up to 310,838 individuals were analyzed. N=55 cases of Alzheimers disease were reported at or before recruitment into UK Biobank. A further N=284 incident cases were identified over follow-up. Multivariable observational analysis of the prevalent cases suggested significant impacts on costs ({pound}1,140 in cases, 95% Confidence Interval (CI): {pound}825 to {pound}1,456) and QALYs (-25%, 95% CI: -28% to -21%). Mendelian randomization estimates were very imprecise for costs ({pound}3,082, 95% CI: -{pound}7,183 to {pound}13,348) and QALYs (-32%, 95% CI: -149% to 85%), likely due to the small proportion of variance (0.9%) explained in Alzheimers disease status by the most predictive set of SNPs. IMPLICATIONSConventional multivariable models suggested important impacts of Alzheimers disease on inpatient hospital costs and QALYs, although this finding was based on very few cases which may have included instances of early-onset dementia. Mendelian randomization was very imprecise. Larger GWAS of clinical cases, improved understanding of the architecture of the disease, and the follow-up of cohorts until old age and death will help overcome these challenges.

BackgroundOlder adults and those with underlying health conditions were advised to stay at home to help reduce the spread of COVID-19 however little advice on regular physical activity was given to those at risk. We modelled the effects of enforced inactivity on diabetes burden using published evidence. MethodsUsing Health Survey for England data, we estimated the prevalence of pre-diabetes and physical activity in adults aged 70 and older. The number of new diabetes cases directly attributed to lockdown were calculated using population attributable risk. Unit cost estimates of the additional burden on primary care and the cost of complications to secondary care were taken from the literature. ResultsFrom 9 million older ([&ge;]70yrs) people living in England, 2.1 million could be defined as pre-diabetic (glycated haemoglobin 42<48 mmol/mol). The estimated population attributable fraction (0.281) (assuming relative risk of diabetes from inactivity=3.3, 40% physically active) would give rise to 392,948 new cases of diabetes which we argue are directly attributed to a prolonged period of lockdown. We estimate that the cost of screening and testing these patients in primary care ({pound}35m), their subsequent treatment and management ({pound}229m), and complications ({pound}909m) would equate to an additional {pound}1.17bn to the health care system. ConclusionsInactivity related to lockdown in previously active older adults may contribute up to {pound}1.17b in additional healthcare costs through a potential increase in diabetes. Clear advice about the importance of physical activity may reduce this potential economic burden during global pandemics.

BackgroundTo inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents. MethodsWe performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort study with inclusion of nursing home residents in Sweden. We analyzed immunological and registry data collected from September 2021 with end of follow-up 31 August 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves. FindingsA total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG among 2606 blood-sampled individuals and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted the levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The risk plateaued at population average above lower 35th percentile of S-binding IgG. InterpretationIn the absence of neutralizing antibodies that protection from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal Covid-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern. FundingSwedish Research Council, SciLife, Knut and Alice Wallenberg Foundation and Vinnova.

BackgroundRegular exercise and community engagement may slow the rate of function loss for people with dementia. However, the evidence is uncertain regarding the cost-effectiveness and social return on investment (SROI) of home exercise with community referral for people with dementia. This study aimed to compare the social value generated from the in-person PrAISED programme delivered before March 2020 with a blended PrAISED programme delivered after March 2020. MethodsSROI analysis was conducted alongside a randomised controlled trial (RCT). Of 205 patient participants and their carers who completed cost data, 61 completed an in-person programme before March 2020. Due to COVID-19 pandemic restrictions, 144 patient participants completed a blended programme consisting of a combination of in-person visits, phone calls and video conferencing with multidisciplinary team (MDT) members. SROI analysis compared in-person and blended delivery formats. Five relevant and material outcomes were identified: three outcomes for patient participants (fear of falling, health-related quality of life, and social connection); one outcome for carer participants (carer strain index), and one outcome for the NHS (health service resource use). Data were collected at baseline and a 12-month follow-up. ResultsThe in-person PrAISED programme generated SROI ratios ranging from {pound}0.58 to {pound}2.33 for every {pound}1 invested. In-person PrAISED patient participants gained social value from improved health-related quality of life, social connection, and less fear of falling. In-person PrAISED carer participants acquired social value from less carer strain. The NHS gained benefit from less health care service resource use. However, the blended PrAISED programme generated lower SROI ratios ranging from a negative ratio to {pound}0.08: {pound}1. ConclusionCompared with the blended programme, the PrAISED in-person programme generated higher SROI ratios for people with early dementia. During the COVID-19 pandemic and its restrictions, a blended delivery of the programme and the curtailment of community activities resulted in lower SROI ratios during this period. An in-person PrAISED intervention with community referral is likely to provide better value for money than a blended one with limited community referral, despite the greater costs of the former. Trial registrationISRCTN15320670

BackgroundThe high cost and widespread use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a concern for healthcare budgets. Whether GLP-1RA use reduces other health care spending is unclear. MethodsWe conducted a cohort study using insurance claims data for United States adults aged 18-64 from 2016-2024, matching GLP-1RA treated members with untreated members (controls) on baseline demographics, clinical conditions, hospitalization, and medication use. Primary outcomes were per member per month (PMPM) healthcare costs overall and by service type, analyzed separately for members with and without diabetes. ResultsAmong 742,824 matched treated and control members, 55.6% had diabetes. In year 1 following GLP-1RA initiation, total costs were 68.7% higher in treated members (95% CI, 68.0%-69.4%, $743 PMPM difference); in years 2-6 costs were 44.8% higher (95% CI, 43.7%-45.9%; $530 PMPM difference). Excluding GLP-1RA costs, treated members had 5.8% higher costs in year 1 (95% CI 5.1%-6.5%) and 4.1% higher costs (95% CI 3.0% - 5.2%) in years 2-6. Among treated members with diabetes, cost increases were modest: 3.8% (95% CI 2.8% - 4.8%) in year 1 and 0.8% in years 2-6 (95% CI 0.6%-2.2%), with non-GLP-1RA pharmacy and provider visits offset by reduced admissions and dialysis. Treated members without diabetes had more substantial cost increases: 8.9% in year 1 (95% CI 7.7% - 10.1%) and 9.7% in years 2-6 (95% CI 8.0% - 11.4%). ConclusionsGLP-1RA treatment was associated with increases in spending on healthcare net of the GLP-1RA cost, particularly in members without diabetes. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the real-world costs of GLP-1 receptor agonist (GLP-1RA) treatment for adults with diabetes and other conditions? FindingsGLP-1RAs treatment is associated with substantially increased healthcare costs. Excluding the costs of GLP-1RAs, treated adults with diabetes have modest increases in costs; however, those treated without diabetes have costs that are.9% higher than those not receiving the drug. MeaningMedical costs of using GLP-1RAs for those without diabetes go far beyond the costs of the agents. An estimated 40% of the US adult population are eligible for treatment for obesity. Treating them with GLP-1RAs would have a substantial impact on insurance costs.

IntroductionThis study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during Englands Delta wave, by age group, dose, and over time. MethodsWe used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine. ResultsCompared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18-29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60-69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose. ConclusionImportant demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during Englands Delta wave, with evidence of waning predominantly restricted to those aged 70+.

Purpose: Neurogenic dysphagia is prevalent in neurological inpatients and associated with adverse outcomes, yet its independent economic impact after adjustment for frailty and functional status remains poorly quantified. We aimed to estimate the independent effect of dysphagia on hospital length of stay (LOS) and costs, to test whether this effect differs between geriatric and non-geriatric patients, and to quantify the probability and magnitude of cost savings from improvements in swallowing function. Methods: We analysed 10,375 neurological inpatient cases (2021-2024) at a German university hospital. Dysphagia was defined by fiberoptic endoscopic evaluation of swallowing (FEES) or ICD-10 R13 coding (n = 1,382; 13.3%). Bayesian Gamma-log regression with informative priors from historical data and published literature was used to model LOS and total case costs (German DRG), adjusted for age, sex, Hospital Frailty Risk Score (HFRS, R13-adjusted), self-care index ("Selbstpflege-Index", SPI), stroke status, and emergency admission. A geriatric cohort was defined as age >=70 and adjusted HFRS >=5 (n = 2,053; 19.8%). Posterior predictive simulation estimated cost savings for hypothetical improvements of 1-3 points on the Functional Oral Intake Scale (FOIS). Results: After comprehensive adjustment, dysphagia was independently associated with 46.5% longer LOS (posterior ratio 1.465; 95% credible interval [CrI] 1.397-1.537) and 28.2% higher total case costs (ratio 1.282; CrI 1.213-1.354). The dysphagia x geriatric interaction was small but credible and ran in opposite directions: slightly attenuated for LOS (interaction ratio 0.908, CrI 0.837-0.986) but slightly amplified for costs (1.096, CrI 1.012-1.185), consistent with complexity-driven DRG grouping in geriatric patients. The absolute economic burden remained larger in the geriatric cohort due to higher baseline costs. In the geriatric cohort, a one-point FOIS improvement yielded a 74.3% posterior probability of LOS-based savings (mean EUR 555/case); at three points, this rose to 84.2% (mean EUR 1,115/case). The direct cost model confirmed high benefit probabilities from the payer's perspective (82.6% at dFOIS = 3). Conclusions: Neurogenic dysphagia is an independent and substantial driver of hospital LOS and costs in neurological inpatients, even after adjustment for frailty and functional status. The proportional effect on costs is slightly larger in geriatric patients, while the LOS effect is slightly smaller, consistent with the mechanics of the G-DRG system. Bayesian simulation indicates that improvements in swallowing function carry a high probability of generating cost savings, supporting the characterisation of dysphagia as a modifiable economic target with particular relevance to geriatric neurology.

BackgroundLong COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. MethodsWith the approval of NHS England, we developed OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. ResultsWe used data from 6,070 participants where 24.7% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a high probability of reporting loss in quality-of-life (OR: 22, 95% CI:12.35-39.29) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 60.2, 95% CI: 27.79-130.57) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. ConclusionsWe found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease.

BackgroundThe effectiveness of exercise interventions to improve activities of daily living function in people with dementia is inconclusive. This study aimed to assess the long-term cost-effectiveness of the PrAISED intervention from a National Health Service (NHS) perspective. MethodThis novel robust economic analysis used a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) over a lifetime horizon of 15 years for a cohort of patients. Sensitivity analyses were conducted to investigate the uncertainty and robustness of high-impacting parameters and results. ResultsThis study included 365 adults, aged 65 years and above with 183 and 182 randomised to the PrAISED and standard care groups respectively. The PrAISED intervention had mean per-patient cost of {pound}60,465 for the PrAISED arm and {pound}54,604 for standard care. The Praised intervention gained an incremental QALYs of 0.05 resulting in an ICER of {pound}129,614 per QALY. The sensitivity analysis of the intervention cost varied the ICER value between {pound}68,173 and {pound}191,054/QALY. To achieve the recommended NICE willingness to pay threshold value of less than {pound}30,000/QALYs would require the intervention cost to be reduced from {pound}1,236 (current cost) to {pound}263 to break even and be cost-effective. The sensitivity analyses revealed that there was a 40% probability of standard care dominating the PrAISED treatment. ConclusionsAlthough the PrAISED intervention was a low-cost intervention, it did not produce a cost-effective intervention in this analysis. The flexibility of the PrAISED program to adapt to government policy during the COVID-19 pandemic was positive. Trial registrationISRCTN15320670

BackgroundDisease-modifying therapies (DMTs) for Alzheimers disease, including lecanemab and donanemab, have received regulatory approval in multiple jurisdictions. These therapies require complex diagnostic workup and safety monitoring, raising significant budget impact concerns for healthcare payers. No budget impact analysis specific to Ireland or comparable small European healthcare systems has been published. ObjectiveTo estimate the 5-year budget impact of introducing DMTs for early-stage Alzheimers disease in Ireland from the Health Service Executive (HSE) payer perspective. MethodsA budget impact model was developed following International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. The model incorporated Irish epidemiological data, published drug prices, and healthcare resource utilisation estimates. Three treatment uptake scenarios (conservative, base case, optimistic) were modelled over a 5-year time horizon. Sensitivity analyses examined parameter uncertainty. ResultsFrom an estimated eligible population of 11,568 individuals with early-stage Alzheimers disease, annual budget impact in Year 5 ranged from {euro}12.8 million (conservative: 3% uptake) to {euro}89.6 million (optimistic: 20% uptake), with a base case estimate of {euro}35.8 million (8% uptake). Cumulative 5-year budget impact ranged from {euro}32.0 million to {euro}224.0 million. Drug acquisition costs represented 61% of total expenditure, with diagnostic and monitoring costs comprising 24% and 15%, respectively. Sensitivity analysis identified drug price, eligible population size, and treatment uptake as the most influential parameters. ConclusionsIntroduction of DMTs for Alzheimers disease will have a substantial but manageable budget impact on the Irish healthcare system, contingent on treatment uptake rates constrained by diagnostic capacity. Strategic investment in diagnostic infrastructure, phased implementation, and negotiated drug pricing could mitigate budgetary pressures while enabling patient access to these novel therapies. Key Points for Decision MakersO_LIThis is the first budget impact analysis of disease-modifying therapies (DMTs) for Alzheimers disease specific to Ireland, a small European healthcare system with constrained diagnostic capacity. C_LIO_LIAnnual budget impact ranges from {euro}12.8 million (conservative scenario) to {euro}89.6 million (optimistic scenario) in Year 5, representing 0.05% to 0.33% of the total Health Service Executive budget. C_LIO_LIDrug acquisition costs account for 58-65% of total expenditure, with diagnostic workup and safety monitoring comprising substantial ancillary costs. C_LIO_LIPhased implementation aligned with diagnostic infrastructure expansion could enable budget-neutral introduction through efficiency gains in dementia care pathways. C_LI

Structured AbstractO_ST_ABSImportanceC_ST_ABSType 2 diabetes and obesity drive substantial morbidity and spending. Rigorous evidence on the impacts of digitally delivered lifestyle interventions on healthcare cost and utilization are critical to assessing their value. ObjectiveDetermine the impact of a telehealth-delivered individualized nutrition therapy (INT) program on per-member-per-month (PMPM) total cost of care and utilization over one and two years. DesignRetrospective propensity score matched difference-in-differences analysis of cost and utilization outcomes over the study period of January 2016-March 2025. SettingUS adults participating in a telehealth T2D and obesity management program. ParticipantsEnrolled in INT for >1 day or had PCP visit for T2D or obesity during study period; had [&ge;]12 months pre-index and [&ge;]90 days post-index claims coverage (allowing [&le;]30-day gaps). Final matched sample: 6,580 participants and 6,580 controls (per arm: 3,819 with type 2 diabetes and 2,761 with obesity). ExposuresTelehealth-delivered, continuous care integrating individualized carbohydrate-reduced nutrition support, clinician-guided medication management, health coaching, and remote biometric monitoring. Main Outcomes and MeasuresOutcomes included PMPM allowed inpatient, outpatient, and prescription medication costs, inpatient, emergency department, primary care, cardiology, and endocrinology visits. For the T2D cohort, PMPM spending and proportion of days covered for each T2D medication. ResultsAmong 3,819 adults with T2D and 2,761 adults with obesity, program participation was associated with $240 and $256 PMPM reductions in the total cost of care at 12 months (-$230 and $189 over 24 months, all P<.001). In the T2D cohort, savings were driven by deprescription of SGLT2 inhibitors (66.8% reduction in PMPM cost), sulfonylureas (51.7%), insulin (43.9%), and GLP-1s (32.2%). In the obesity cohort, reductions accrued across inpatient, outpatient and prescription medication settings. Conclusions and RelevanceIn this large, real-world analysis, a nutrition-first digital care model was associated with sustained reductions in cost and utilization over 12-24 months, with immediate prescription medication cost reductions in the cohort with T2D and broader savings in the cohort with obesity. Together with prior clinical evidence, these findings suggest alignment of clinical effectiveness and cost reductions of a telehealth-delivered lifestyle intervention. Key pointsO_ST_ABSQuestionC_ST_ABSIs participation in a telehealth-delivered individualized nutrition therapy program associated with changes in healthcare costs and utilization among adults with type 2 diabetes (T2D) or obesity? FindingsIn this retrospective cohort study of 13,000 matched adults, participation was associated with lower total cost of care at one year (-$240 and -$256 for adults with T2D and obesity respectively) and over two years (T2D: -$230; obesity: $-189). Among adults with T2D, reductions were driven by inpatient costs and all T2D medications, including GLP-1s. Among adults with obesity, reductions occurred across inpatient, outpatient, and prescription medication costs. MeaningTelehealth-delivered nutrition therapy may reduce healthcare spending for adults with T2D or obesity.

ObjectiveTo evaluate whether home-based extended rehabilitation for older people with frailty after hospitalisation with an acute illness or injury can improve physical health-related quality of life and is cost-effective. Trial designPragmatic, multi-centre, individually randomised controlled parallel group superiority trial with economic evaluation and embedded process evaluation. SettingRecruitment from 15 NHS Trusts in England, with home-based intervention delivery. ParticipantsEligible participants were 65 years or older with mild/moderate/severe frailty (score of 5-7 on Clinical Frailty Scale) admitted to hospital with acute illness/injury, then discharged home directly, or from intermediate care (post-acute care) rehabilitation services. Recruitment took place December 2017 to August 2021, with follow-up to August 2022. InterventionsParticipants were randomly assigned (1.28:1) to the Home-based Older Peoples Exercise (HOPE) programme - a 24-week home-based manualised, progressive exercise intervention as extended rehabilitation, or usual care (control). Participants were not masked to allocation. Main outcome measuresPrimary outcome was physical health-related quality of life, measured using the physical component summary (PCS) of the modified Short Form 36-item health questionnaire (SF36) at 12 months. Secondary outcomes at six and 12 months included physical and mental health-related quality of life, functional independence, death, hospitalisations and care home admissions. Researchers involved in data collection were masked to allocation. ResultsWe randomised 740 participants (410 HOPE, 330 control) across 15 sites. 479 (64.7%) participants completed 12-month follow-up. 188 HOPE participants (45.9%) completed 24 weeks of intervention delivery. Over half of participants completed more than 75% of prescribed exercises. Intention-to-treat analyses showed no evidence that HOPE was superior to control for 12-month PCS score (adjusted mean difference -0.22, 95% CI -1.47 to 1.03; p = 0.73). There was some evidence of a higher rate of all-cause hospitalisations in the control arm (incidence rate ratio 1.12, 95% CI 1.00 to 1.25; p = 0.05), but no differences in other outcomes. The process evaluation found the intervention was largely delivered as intended and proved acceptable to most participants. The economic analysis showed HOPE plus usual care costs of GB{pound}1,401 with 0.024 QALY improvement compared to the control. Incremental cost-effectiveness ratio GB{pound}58,375. LimitationsThe HERO trial was delivered during especially challenging circumstances that included the COVID-19 pandemic. We examined outcomes taking account of this but detected no difference in primary or secondary outcomes, providing reassurance that COVID-19 was unlikely to have influenced trial results. ConclusionsBased on our findings, we do not recommend routine commissioning of extended rehabilitation for older people with frailty after discharge home from hospital or intermediate care, following an acute admission with a medical illness or injury. Trial registrationISRCTN-13927531 (19/04/2017).

BackgroundWith shifting epidemiology and changes in the vaccine funding landscape, resource use considerations for ongoing COVID-19 vaccination programs are increasingly important. We assessed the cost-effectiveness of COVID-19 vaccination programs, where eligibility is defined by combinations of age and chronic medical conditions, including a strategy similar to current Canadian recommendations, from the health system and societal perspectives. MethodsWe used a static, individual-based probabilistic model simulating medically attended COVID-19 in a population of 1 million people followed over a 15-month time period to estimate costs in 2023 Canadian dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 1.5%. COVID-19 epidemiology, vaccine characteristics, and costs were based on the most recently available data. ResultsAnnual vaccination for adults aged 65 years and older consistently emerged as a cost-effective intervention, with ICERs less than $50,000 per QALY compared to no vaccination for a range of model assumptions. Adding a second dose for adults aged 65 years and older or expanding programs to include vaccination for younger age groups, including those at higher risk of COVID-19 due to chronic medical conditions, generally resulted in ICERs of greater than $50,000 per QALY. Shifting timing of vaccination programs to better align with periods of high COVID-19 case occurrence could result in biannual vaccination for those aged 65 and older being a cost-effective strategy. ConclusionsCOVID-19 vaccination programs may be cost-effective when focused on groups at higher risk of disease. Optimal timing of vaccination could improve the cost-effectiveness of various strategies.

BackgroundDementia diagnoses are captured across multiple routine data sources, but discrepancies between these may affect care and research. This study determined the prevalence and overlap of recorded dementia across primary care, hospital, and community prescribing data sources in a UK regional cohort, and examined whether outcomes differed by the setting in which dementia was first recorded. MethodsRetrospective cohort study of adults [&ge;]65 years (n=133,407) in a large Scottish health board. Dementia diagnoses recorded from 01/04/2016 to 01/04/2020 were identified across linked primary care, hospital discharge, and prescribing records. Associations between source of first recorded dementia diagnosis and subsequent mortality and emergency hospitalisation were estimated using Cox proportional hazards and Fine-Gray competing risks models. ResultsAt baseline (01/04/2016), 7544/133407 individuals (5.7%) had recorded dementia: 95.1% in primary care, 73.3% in hospital, and 54.3% in prescribing records. Over four years, 7359 of the remaining 125,863 individuals (5.8%) had newly recorded dementia: 70.2% in primary care, 22.2% in hospital, and 7.6% in prescribing records. Only 35.9% of hospital-recorded diagnoses were coded in primary care records within a year. People first diagnosed in hospital were older, more frail, more socioeconomically deprived, and had higher mortality than those first diagnosed in primary care (<30days: adjusted Hazard Ratio (aHR) 8.96, 95%CI 6.94-13.52; >365days: aHR 1.29, 95%CI 1.19-1.41). ConclusionsDementia is variably recorded across routine datasets, and the setting in which dementia is first recorded identifies groups with markedly different prognosis. Improved data source integration and scrutiny of hospital-based diagnostic pathways are needed to ensure diagnoses are reliably transferred and people with dementia receive timely, equitable post-diagnostic care.

BackgroundNon-specific live vaccine effects have been described in paediatric populations. We investigated whether non-specific effects are observed in older adults with live shingles (Zostavax(R)) immunisation. MethodsA population-based cohort study was performed using primary- and secondary-care data from the Clinical Practice Research Datalink in England. Shingles vaccine eligible individuals aged 70 years and over who had received pneumococcal immunisation were included. All-cause death, all-cause hospitalisation, and infection-associated hospitalisation rates were compared between live shingles vaccinated and unvaccinated person-time using time-to-first-event Cox regression and recurrent events modelling. Live shingles vaccine exposure was included as a time-varying exposure. The models were run on an overlap-weighted pseudo-population to minimise confounding. FindingsBetween September 2013 and June 2019 314,618 participants aged 70 years and over who had received pneumococcal immunisation prior to study entry were identified, of which 55% had live shingles vaccine exposure. The overlap weighted pseudo-population consisted of 60021 lives shingles vaccine unexposed and 60245{middle dot}6 exposed participants. Live shingles vaccine exposure in the overlap pseudo-population was associated with a reduction in all-cause death (hazard ratio 0{middle dot}64; 95% confidence interval 0{middle dot}62, 0{middle dot}66), a reduction in recurrent all-cause hospitalisation (hazard ratio 0{middle dot}83 (0{middle dot}79, 0{middle dot}87)), and a reduction in first and recurrent infection-associated hospitalisation (hazard ratio for first event 0{middle dot}81 (0{middle dot}79, 0{middle dot}83), and for recurrent events 0.75 (0.73, 0.77)). Protective vaccine effects were observed for at least five years post-immunisation. InterpretationsReceipt of live shingles vaccine associates with lower mortality and morbidity in older adults in England. The potential for causal linkage should be validated in robust prospective studies, with major implications for national immunisation policies. FundingNo specific funding for this project. KD was supported by an NIHR academic clinical fellowship. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA body of research exists demonstrating an association between live vaccines and a reduction in mortality and illness unrelated to the vaccine target. This has been termed non-specific vaccine effects for which heterologous immune programming has been proposed as a possible mechanism. To date, non-specific vaccine effects have largely been demonstrated in paediatric populations in relation to live measles, oral polio, and Bacillus Calmette-Guerin (BCG) immunisation. Added value of this studyThis is the first study to evaluate mortality and hospitalisation effects in an older adult population with live shingles immunisation. Older adults are a growing population in many settings worldwide and require cost-effective interventions to reduce morbidity and mortality. This study finds a reduction in all-cause death, all-cause hospitalisation, and infection-associated hospitalisation in over 70-year-olds in England associated with live shingles vaccine exposure. These findings were not explained by any measurable confounding effect of age, socio-economic status, comorbidity, nor health-seeking behaviour. Implications of all the available evidenceThis work and other emerging reports advocate for studies with an experimental design to provide definitive evidence of non-specific vaccine effects to guide policy makers and to evaluate the possible immune mechanisms in an older immunosenescent population. There is potential for very significant benefits relating to both use of shingles vaccine and type of vaccine that needs clarity.

BackgroundLong Covid has emerged as a complex health condition for millions of people worldwide following the COVID-19 pandemic. Previously, we have categorised healthcare pathways for patients after discharge from hospital with COVID-19 across 45 UK sites. The aim of this work was to estimate the clinical and cost-effectiveness of these pathways. MethodsWe examined prospectively collected data from 1,013 patients at 12-months post-discharge on whether they felt fully recovered (self-report), number of newly diagnosed conditions (NDC), quality of life (EQ-5D-5L utility score compared to pre-covid estimate) and healthcare resource costs (healthcare records). An analysis of the cost-effectiveness was performed by combining the healthcare resource cost and one-year EQ5D (giving a quality adjusted life-year: QALY) using statistical models that accounted for observed confounding. ResultsAt 1 year, 29% of participants felt fully recovered and 41% of patients had an NDC. The most comprehensive services, where all patients could potentially access assessment, rehabilitation, and mental health services, were more clinically effective when compared with either no service or light touch services (mean (SE) QALY 0.789 (0.012) vs 0.725 (0.026)), with an estimated cost per QALY of {pound}1,700 (95% uncertainty interval: dominated to {pound}24,800). ConclusionOur analysis supports the need for proactive, stratified, comprehensive follow-up for adults after hospitalisation with COVID-19 showing these services are likely to be both clinically and cost-effective according to commonly accepted thresholds.

ObjectiveThanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis health outcomes have improved. This paper evaluates the costs and the health-related quality of life implications of these guidelines. Design and settingA sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015. Study participantsData for patients aged [&ge;]16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months. Primary and secondary outcome measuresPatient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS), and the EuroQoL; health care costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life years (QALYs) were calculated from the EQ-5D utility scores. Cost-utility analysis was performed using the NHS and Social Scare perspective. ResultsA total of 49 patients were included, 35 treated within 48 hours "early" (median [IQR] 8.25 [3.7-20.5]) and 14 treated after 48 hours (median [IQR] 93.9 [66.7 - 100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0-3) compared to 4 (29%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p<0.000). After adjusting for age and symptom duration at admission, early treatment incurred a lower average cost at discharge, {pound}23,086 (95% CI: {pound}15,186 to {pound}30,987) vs {pound}42,405 (95% CI: {pound}25,457 to {pound}59,354) [p<0.04]. A -{pound}20,218 (95% CI: -{pound}52,173 to {pound}11,783) cost difference was observed at 12-month follow-up post discharge. ConclusionsThis study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment. Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABS- Admissions to acute hospitals with suspected encephalitis, using predetermined inclusion criteria were recruited across 29 hospitals in the UK within a 3-year period, giving the largest cohort of prospectively recruited HSV encephalitis cases in the UK to date. - Precise definitions to characterise those individuals with proven HSV encephalitis were applied thus ensuring accurate diagnoses. - Individuals were followed up systematically for 12 months after discharge for clinical, and quality of life data providing the first study to assess the effect of treatment delays on health care resources, costs and health related quality of life. - The analysis is limited by its relatively small sample size due to it being a rare disease, and the case record forms although thorough may not capture all health care costs incurred. This is particularly so for primary care and community care contact outside of the study hospitals.

AimsCOVID-19 disease burden in United States (US) older adults [&ge;]65 years and persons with underlying medical conditions remains high. This modeling study provides an interim estimate of the anticipated public health impact of the next-generation COVID-19 mRNA-1283 vaccine in these populations at high-risk of severe COVID-19 outcomes. MethodsmRNA-1283 was compared to no vaccination and originally licensed mRNA COVID-19 vaccines mRNA-1273 and BNT162b2. Analyses were conducted using a static decision-analytic model (1-year horizon). Vaccine effectiveness (VE) against infection and hospitalization for mRNA-1283 versus no vaccination was based on the relative VE (rVE) from the Phase 3 pivotal randomized controlled trial comparing mRNA-1283 against mRNA-1273 and mRNA-1273 real-world data. rVE estimates for mRNA-1283 versus BNT162b2 were based on an indirect treatment comparison. Clinical outcomes calculated included total numbers of symptomatic infections, outpatient and long COVID cases, hospitalizations, and deaths. Sensitivity and scenario analyses were performed. ResultsDuring the 2024/2025 season in the US, a single dose of the mRNA-1283 vaccine was estimated to prevent approximately 2.9 (1.3-4.3) million symptomatic infections, 171,000 (77,000-260,000) hospitalizations, and 22,350 (10,050-33,480) deaths compared to no vaccination. Compared to BNT162b2, mRNA-1283 was estimated to avert an additional 0.79 million symptomatic infections, 58,000 hospitalizations, and 7,565 deaths. Compared to mRNA-1273, mRNA-1283 was estimated to avert an additional 0.56 million symptomatic infections, 46,000 hospitalizations, and 5,920 deaths. Across all scenarios the majority of severe COVID-19 cases (i.e., hospitalizations and deaths) were prevented among older adults [&ge;]65 years. LimitationsThe real-world effectiveness and safety of mRNA-1283 have not yet been established and the relative VE estimates should be validated with real-world data. Future COVID-19 incidence and incidence pattern throughout the season is uncertain. ConclusionsInterim results suggest that the next-generation COVID-19 mRNA-1283 vaccine could substantially reduce the clinical burden of COVID-19 among those at high risk of severe disease. Compared to no vaccination and originally approved mRNA vaccines, mRNA-1283 provides a valuable option to potentially enhance COVID-19 immunization programmes and protection of those most vulnerable.

ObjectivesThe aim of this study was to develop a comprehensive economic evaluation of the Integrated Cognitive Assessment (ICA) tool compared with standard cognitive tests when used for dementia screening in primary care and for initial patient triage in memory clinics. MethodsICA was compared with standard of care comprising a mixture of cognitive assessment tools over a lifetime horizon and employing the UK health and social care perspective. The model combined a decision tree to capture the initial outcomes of the cognitive testing with a Markov structure that estimated long-term outcomes of people with dementia. Quality of life outcomes were quantified using quality-adjusted life years (QALYs). Both costs and QALYs were discounted at 3.5% per annum and cost-effectiveness was assessed using a threshold of {pound}20,000 per QALY gained. ResultsICA dominated standard cognitive assessment tools in both the primary care and memory clinic settings. Introduction of the ICA tool was estimated to result in a lifetime cost saving of approximately {pound}147 and {pound}283 per person in primary care and memory clinics, respectively. QALY gains associated with early diagnosis were modest (0.0019 in primary care and 0.0035 in memory clinic). The net monetary benefit of ICA introduction was estimated at {pound}184 in the primary care and {pound}368 in the memory clinic settings. ConclusionsIntroduction of ICA as a tool to screen primary care patients for dementia and perform initial triage in memory clinics could be cost saving to the UK public health and social care payer.