Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation.

Aims: Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start. Methods and results: This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39-2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42-2.14). Conclusion: Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.

Health financing challenges in Southeast Asian countries for universal health coverage: a systematic review.

BACKGROUND: Universal Health Coverage (UHC) has received much attention and many countries are striving to achieve it. The Southeast Asian region, in particular, comprises many developing countries with limited resources, exacerbating challenges around attaining UHC. This paper aims to specifically explore the health financing challenges these countries face in achieving UHC via a systematic review approach and formulate recommendations that will be useful for policymakers. METHODS: The systematic review followed the guidelines as recommended by PRISMA. The narrative synthesis approach was used for data synthesis, followed by identifying common themes. RESULTS: The initial search returned 160 articles, and 32 articles were included after the screening process. The identified challenges in health financing towards achieving UHC in the Southeast Asian region are categorised into six main themes, namely (1) Unsustainability of revenue-raising methods, (2) Fragmented health insurance schemes, (3) Incongruity between insurance benefits and people's needs, (4) Political and legislative indifference, (5) Intractable and rapidly rising healthcare cost, (6) Morally reprehensible behaviours. CONCLUSIONS: The challenges identified are diverse and therefore require a multifaceted approach. Regional collaborative efforts between countries will play an essential role in the progress towards UHC and in narrowing the inequity gap. At the national level, individual countries must work towards sustainable health financing strategies by leveraging innovative digital technologies and constantly adapting to dynamic health trends. REGISTRATION: This study is registered with PROSPERO, under registration number CRD42022336624.

How do multiple long-term conditions impact on the cost-of-illness in early rheumatoid arthritis?

OBJECTIVE: Multiple long-term conditions (MLTCs) are prevalent in rheumatoid arthritis (RA) and associated with worse outcomes and greater economic burden. However, little is known about the impact of MLTCs on the cost-of-illness (COI) in early RA, including direct and indirect costs. The objective of this study was to quantify this impact on COI. METHODS: The Scottish Early Rheumatoid Arthritis study is a national cohort of adults with new-onset RA. Direct costs were estimated applying relevant unit costs to health resource utilisation; indirect costs were measured by productivity loss due to health conditions. Two-part models were used, adjusting for age, gender, baseline functional disability and health-related quality of life. The Charlson Comorbidity Index score was calculated using ICD-10 diagnoses. Individuals were defined as 'RA alone', 'RA plus LTC' and 'RA plus MLTCs' according to the number of coexisting LTCs. RESULTS: Data were available for 818 participants. Average annualised direct costs incurred by people with early RA plus MLTCs (£4444; 95% CI £3100 to £6371) were twice as, and almost five times higher than, those with a single LTC (£2184; 95% CI £1596 to £2997) and those without LTC (£919; 95% CI £694 to £1218), respectively. Indirect costs incurred by RA plus MLTCs (£842; 95% CI £377to £1521) were 3.1 times higher than RA alone (£530; 95% CI £273to £854). The relative proportion of direct costs increased with LTC category, ranging from 77.2% to 84.1%. In addition to increased costs with LTCs, costs also increased with age and were higher for men regardless of LTC category. CONCLUSIONS: MLTCs impact on COI early in the course of RA. The presence of LTCs is associated with significant increases in both direct and indirect costs among people with early RA.

Propensity score methods for comparative-effectiveness analysis: A case study of direct oral anticoagulants in the atrial fibrillation population.

OBJECTIVE: To explore methodological challenges when using real-world evidence (RWE) to estimate comparative-effectiveness in the context of Health Technology Assessment of direct oral anticoagulants (DOACs) in Scotland. METHODS: We used linkage data from the Prescribing Information System (PIS), Scottish Morbidity Records (SMR) and mortality records for newly anticoagulated patients to explore methodological challenges in the use of Propensity score (PS) matching, Inverse Probability Weighting (IPW) and covariate adjustment with PS. Model performance was assessed by standardised difference. Clinical outcomes (stroke and major bleeding) and mortality were compared for all DOACs (including apixaban, dabigatran and rivaroxaban) versus warfarin. Patients were followed for 2 years from first oral anticoagulant prescription to first clinical event or death. Censoring was applied for treatment switching or discontinuation. RESULTS: Overall, a good balance of patients' covariates was obtained with every PS model tested. IPW was found to be the best performing method in assessing covariate balance when applied to subgroups with relatively large sample sizes (combined-DOACs versus warfarin). With the IPTW-IPCW approach, the treatment effect tends to be larger, but still in line with the treatment effect estimated using other PS methods. Covariate adjustment with PS in the outcome model performed well when applied to subgroups with smaller sample sizes (dabigatran versus warfarin), as this method does not require further reduction of sample size, and trimming or truncation of extreme weights. CONCLUSION: The choice of adequate PS methods may vary according to the characteristics of the data. If assumptions of unobserved confounding hold, multiple approaches should be identified and tested. PS based methods can be implemented using routinely collected linked data, thus supporting Health Technology decision-making.

Evaluating stroke early supported discharge using cost-consequence analysis.

PURPOSE: To evaluate different stroke early supported discharge (ESD) services in different geographical settings using cost-consequence analysis (CCA), which presents information about costs and outcomes in the form of a balance sheet. ESD is a multidisciplinary service intervention that facilitates discharge from hospital and includes delivery of stroke specialist rehabilitation at home. MATERIALS AND METHODS: Data were collected from six purposively sampled services across the Midlands, East and North of England. All services, rural and urban, provided stroke rehabilitation to patients in their own homes. Cost data included direct and overhead costs of service provision and staff travel. Consequence data included service level adherence to an expert consensus regarding the specification of ESD service provision. RESULTS: We observed that the most rural services had the highest service cost per patient. The main costs associated with running each ESD service were staff costs. In terms of the consequences, there was a positive association between service costs per patient and greater adherence to meeting the evidence-based ESD service specification agreed by an expert panel. CONCLUSIONS: This study found that rural services were associated with higher costs per patient, which in turn were associated with greater adherence to the expert consensus regarding ESD service specification. We suggest additional resources and costs are required in order for rural services to meet evidence-based criteria.Implications for rehabilitationThe main costs of an early supported discharge (ESD) service for stroke survivors were staff costs and these were positively associated with greater levels of rurality.Greater costs were associated with greater adherence to ESD core components, which has been previously found to enhance the effectiveness of ESD service provision.The cost-consequence analysis provides a descriptive summary for decision-makers about the costs of delivering ESD, suggesting additional resources and costs are required in order for rural services to meet evidence-based criteria.

Healthcare Costs for Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone or Enzalutamide.

OBJECTIVE: The aim was to assess the real-world healthcare resource use and direct medical costs for metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide, in whom chemotherapy is not yet indicated (pre-chemotherapy) or who had previously received docetaxel-based chemotherapy (post-chemotherapy), before commencing these medicines. METHODS: A retrospective cost analysis of mCRPC patients who commenced abiraterone or enzalutamide between 2012 and 2015 was conducted. Routinely collected datasets from the largest health board in Scotland and the UK, Greater Glasgow and Clyde, were linked. They contained information on patient demographics, diagnosis, outpatient consultations, hospital admissions, treatments (abiraterone and enzalutamide), and supportive medicines. Unit costs were obtained from the Scottish Health Service Costs, Personal Social Services Research Unit, and British National Formulary. Generalised linear model-based regression was used to estimate total mean direct costs, and two-part models were used to estimate separate cost components. All models were adjusted for propensity score and key variables. Sensitivity analysis was conducted to explore the impact of hypothetical patient access scheme discounts. RESULTS: Estimated total mean direct medical costs of treating mCRPC patients were similar, albeit with wide and overlapping confidence intervals. Across both treatments, patients who received abiraterone or enzalutamide in a pre-chemotherapy setting incurred the highest total mean direct medical costs. However, post-chemotherapy patients were associated with higher outpatient clinic visits, inpatient hospital admissions, and supportive medicines. Regarding relative contribution to the total mean direct medical cost, the treatment costs were the main contributor, followed by inpatient admissions, outpatient clinic visits, and supportive medicines. CONCLUSION: The total mean direct medical costs were similar for abiraterone and enzalutamide patients. The costs were not driven by the choice of treatment regimen, but treatment setting (pre-chemotherapy or post-chemotherapy indications) and related healthcare resource utilisation. Future studies should focus on economic evaluations, such as cost-effectiveness analyses, using real-world data.

Cost impact of introducing a treatment escalation/limitation plan during patients' last hospital admission before death.

OBJECTIVE: A recent study found that the use of a treatment escalation/limitation plan (TELP) was associated with a significant reduction in non-beneficial interventions (NBIs) and harms in patients admitted acutely who subsequently died. We quantify the economic benefit of the use of a TELP. DESIGN: NBIs were micro-costed. Mean costs for patients with a TELP were compared to patients without a TELP using generalized linear model regression, and results were extrapolated to the Scottish population. SETTING: Medical, surgical and intensive care units of district general hospital in Scotland, UK. PARTICIPANTS: Two hundred and eighty-seven consecutive patients who died over 3 months in 2017. Of these, death was 'expected' in 245 (85.4%) using Gold Standards Framework criteria. INTERVENTION: Treatment escalation/limitation plan. MAIN OUTCOME MEASURE: Between-group difference in estimated mean cost of NBIs. RESULTS: The group with a TELP (n = 152) had a mean reduction in hospital costs due to NBIs of GB £220.29 (US $;281.97) compared to those without a TELP (n = 132) (95% confidence intervals GB £323.31 (US $413.84) to GB £117.27 (US $150.11), P = <0.001). Assuming that a TELP could be put in place for all expected deaths in Scottish hospitals, the potential annual saving would be GB £2.4 million (US $3.1 million) from having a TELP in place for all 'expected' deaths in hospital. CONCLUSIONS: The use of a TELP in an acute hospital setting may result in a reduction in costs attributable to NBIs.

Economic burden of rheumatoid arthritis: a systematic review of literature in biologic era.

BACKGROUND: The past decades have seen rapid advances in the treatment of rheumatoid arthritis (RA). In particular, the introduction of biologic and targeted synthetic disease-modifying antirheumatic drugs have improved clinical outcomes and reconfigured traditional RA cost compositions. OBJECTIVES: To map the existing evidence concerning cost of illness of RA, as the treatment pathway evolves in the biologic era, and examine how costs have been measured and estimated, in order to assemble and appropriately interpret available data. METHODS: Systematic review of studies that estimated the costs of patients with RA. Multiple electronic databases were searched to identify studies published between 2000 and 2019. The reported total costs and cost components were evaluated according to the study and population characteristics. The Cochran-Armitage test was used to determine statistically significant trends in increasing or decreasing proportions over time. RESULTS: Overall, 72 studies were included. Drug costs compromised the main component (up to 87%) of direct costs with an increasing trajectory over time, although not statistically significant. The proportion of costs for hospitalisation showed a statistically significant decrease chronologically (p=0.044). Indirect costs, primarily associated with absenteeism and work disability accounted for 39% to 86% of total costs. The reported indirect costs are highly sensitive to the approach to estimation. CONCLUSIONS: A decreasing trend in inpatient costs chronologically suggested a cost shift in other components of direct costs. Indirect costs still contributed a considerable proportion of total costs, with work disability being the main cost component. Economic analyses that do not incorporate or appropriately measure indirect costs will underestimate the full economic impact of RA.

A two-part model to estimate inpatient, outpatient, prescribing and care home costs associated with atrial fibrillation in Scotland.

OBJECTIVE: This study aimed to estimate global inpatient, outpatient, prescribing and care home costs for patients with atrial fibrillation using population-based, individual-level linked data. DESIGN: A two-part model was employed to estimate the probability of resource utilisation and costs conditional on positive utilisation using individual-level linked data. SETTINGS: Scotland, 5 years following first hospitalisation for AF between 1997 and 2015. PARTICIPANTS: Patients hospitalised with a known diagnosis of AF or atrial flutter. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient, outpatient, prescribing and care home costs. RESULTS: The mean annual cost for a patient with AF was estimated at £3785 (95% CI £3767 to £3804). Inpatient admissions and outpatient visits accounted for 79% and 8% of total costs, respectively; prescriptions and care home stay accounted for 7% and 6% of total costs. Inpatient cost was the main driver across all age groups. While inpatient cost contributions (~80%) were constant between 0 and 84 years, they decreased for patients over 85 years. This is offset by increasing care home cost contributions. Mean annual costs associated with AF increased significantly with increasing number of comorbidities. CONCLUSION: This study used a contemporary and representative cohort, and a comprehensive approach to estimate global costs associated with AF, taking into account resource utilisation beyond hospital care. While overall costs, considerably affected by comorbidity, did not increase with increasing age, care home costs increased proportionally with age. Inpatient admission was the main contributor to the overall financial burden of AF, highlighting the need for improved mechanisms of early diagnosis to prevent hospitalisations.

Cost-effectiveness of treating hepatitis C in Seychelles.

INTRODUCTION: approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment. METHODS: data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs). RESULTS: the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds. CONCLUSION: treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT.

BACKGROUND: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. OBJECTIVE: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. DESIGN: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. SETTING: Twenty-six NHS hospitals. PARTICIPANTS: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). INTERVENTIONS: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. RESULTS: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. LIMITATIONS: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. CONCLUSIONS: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. FUTURE WORK: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91566927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Treatment of bone and joint infection usually requires a long course of antibiotics. Doctors usually give these by injection through a vein (intravenously) for the first 4­6 weeks, rather than by mouth (orally). Although intravenous (IV) administration is more expensive and less convenient for patients, most doctors believe that it is more effective. However, there is little evidence to support this. The OVIVA (Oral Versus IntraVenous Antibiotics) trial set out to challenge this assumption. A total of 1054 patients from 26 UK hospitals were randomly allocated to receive the first 6 weeks of antibiotic therapy either intravenously or orally. Irrespective of the route of administration, the choice of antibiotic was left to an infection specialist so as to ensure that the most appropriate antibiotics were given. Patients were followed up for 1 year. Thirty-nine participants were lost to follow-up. Among the remaining 1015 participants, treatment failure occurred in 14.6% of those treated intravenously and 13.2% of those treated with PO antibiotics. This difference could easily have occurred by chance. Even if it was not by chance, the difference does not suggest that PO therapy is associated with worse outcomes than IV therapy and is too small to conclude that PO therapy is better than IV therapy. Participants in the IV group stayed in hospital longer and 10% of them had complications related to the IV line used for administering the antibiotics. In addition, their treatment was, overall, more expensive. We conclude that PO antibiotic therapy has no disadvantages for the early management of bone and joint infection. It is also cheaper and associated with fewer complications.

A framework for conducting economic evaluations alongside natural experiments.

Internationally, policy makers are increasingly focussed on reducing the detrimental consequences and rising costs associated with unhealthy diets, inactivity, smoking, alcohol and other risk factors on the health of their populations. This has led to an increase in the demand for evidence-based, cost-effective Population Health Interventions (PHIs) to reverse this trend. Given that research designs such as randomised controlled trials (RCTs) are often not suited to the evaluation of PHIs, Natural Experiments (NEs) are now frequently being used as a design to evaluate such complex, preventive PHIs. However, current guidance for economic evaluation focusses on RCT designs and therefore does not address the specific challenges of NE designs. Using such guidance can lead to sub-optimal design, data collection and analysis for NEs, leading to bias in the estimated effectiveness and cost-effectiveness of the PHI. As a consequence, there is a growing recognition of the need to identify a robust methodological framework for the design and conducting of economic evaluations alongside such NEs. This paper outlines the challenges inherent to the design and conduct of economic evaluations of PHIs alongside NEs, providing a comprehensive framework and outlining a research agenda in this area.

Cost-effectiveness of oral versus intravenous antibiotics (OVIVA) in patients with bone and joint infection: evidence from a non-inferiority trial.

Background: Bone and joint infections are becoming increasingly common and are usually treated with surgery and a course of intravenous antibiotics. However, there is no evidence to support the superiority of intravenous therapy and there is a growing body of literature showing that oral therapy is effective in treating these infections.Given this lack of evidence the clinical trial 'Oral Versus Intravenous Antibiotics' (OVIVA) was designed to assess the clinical and cost-effectiveness of intravenous versus oral antibiotics for the treatment of bone and joint infections, using a non-inferiority design. Clinical results from the trial indicate that oral antibiotics are non-inferior to intravenous antibiotics. The aim of this paper is to evaluate the cost-effectiveness of intravenous compared to oral antibiotics for treating bone and joint infections, using data from OVIVA. Methods: A cost-utility analysis was carried out, the main economic outcome measure was the quality adjusted life-year, measured using the EQ-5D-3L questionnaire, combined with costs to estimate cost-effectiveness over 12-months follow-up. Results: Results show that costs were significantly lower in the oral arm compared to the intravenous arm, a difference of £2,740 (95% confidence interval £1,488 to £3,992). Results of four sensitivity analyses were consistent with the base-case results. QALYs were marginally higher in the oral arm, however this difference was not statistically significant; -0.007 (95% confidence interval -0.045 to 0.031). Conclusions: Treating patients with bone and joint infections for the first six weeks of therapy with oral antibiotics is both less costly and does not result in detectable differences in quality of life compared to treatment with intravenous antibiotics. Adopting a practice of treating bone and joint infections with oral antibiotics early in the course of therapy could potentially save the UK National Health Service over £17 million annually.

PATHway I: design and rationale for the investigation of the feasibility, clinical effectiveness and cost-effectiveness of a technology-enabled cardiac rehabilitation platform.

INTRODUCTION: Exercise-based cardiac rehabilitation (CR) independently alters the clinical course of cardiovascular diseases resulting in a significant reduction in all-cause and cardiac mortality. However, only 15%-30% of all eligible patients participate in a phase 2 ambulatory programme. The uptake rate of community-based programmes following phase 2 CR and adherence to long-term exercise is extremely poor. Newer care models, involving telerehabilitation programmes that are delivered remotely, show considerable promise for increasing adherence. In this view, the PATHway (Physical Activity Towards Health) platform was developed and now needs to be evaluated in terms of its feasibility and clinical efficacy. METHODS AND ANALYSIS: In a multicentre randomised controlled pilot trial, 120 participants (m/f, age 40-80 years) completing a phase 2 ambulatory CR programme will be randomised on a 1:1 basis to PATHway or usual care. PATHway involves a comprehensive, internet-enabled, sensor-based home CR platform and provides individualised heart rate monitored exercise programmes (exerclasses and exergames) as the basis on which to provide a personalised lifestyle intervention programme. The control group will receive usual care. Study outcomes will be assessed at baseline, 3 months and 6 months after completion of phase 2 of the CR programme. The primary outcome is the change in active energy expenditure. Secondary outcomes include cardiopulmonary endurance capacity, muscle strength, body composition, cardiovascular risk factors, peripheral endothelial vascular function, patient satisfaction, health-related quality of life (HRQoL), well-being, mediators of behaviour change and safety. HRQoL and healthcare costs will be taken into account in cost-effectiveness evaluation. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki. This protocol has been approved by the director and clinical director of the PATHway study and by the ethical committee of each participating site. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses and events. TRIAL REGISTRATION NUMBER: NCT02717806. This trial is currently in the pre-results stage.

Effect of individual-level and socioeconomic factors on long-term survival after cataract surgery over a 30-year period.

PURPOSE: To evaluate survival and the risk for mortality after cataract surgery in relation to individual-level and socioeconomic factors in Scotland over 3 decades. SETTING: Linked healthcare data, United Kingdom. DESIGN: Representative population-based study. METHODS: A 5% random sample of Scottish decedents linked to hospital records (1981 to 2012) was assessed. Survival time, survival probability, and determinants of mortality were evaluated after the first and second recorded hospital episodes for cataract surgery. Cox proportional-hazards regression models were used to assess the effect of individual-level and socioeconomic factors including age, geographic location, socioeconomic status, and comorbidity on mortality. RESULTS: The study evaluated linked administrative healthcare data from 9228 deceased patients who had cataract surgery. The mean survival time was 2383 days ± 1853 (SD). The survival probability decreased from 98% 90 days after surgery to 22% at 10 years, 2% at 20 years, and 0% after 30 years. The mean age was 77 ± 9 years. Age (hazard ratio [HR] 3.66; 95% confidence interval [CI], 2.97-3.80; P < .001) and severe comorbidity (HR 1.68; 95% CI, 1.47-1.91; P < .001) were associated with an increased risk for mortality; women had a 20% lower risk than men (HR 0.80; 95% CI, 0.76-0.83; P < .001). Socioeconomic status and rural geographic locations were not linked to mortality. CONCLUSIONS: Long-term survival after cataract surgery was determined by individual-level characteristics reflecting the mortality patterns of aging populations. The mortality risk was independent of socioeconomic and geographic factors per se.

The SCottish Alcoholic Liver disease Evaluation: A Population-Level Matched Cohort Study of Hospital-Based Costs, 1991-2011.

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses.

Geographic variation of inpatient care costs at the end of life.

BACKGROUND: costs incurred at the end of life are a main contributor to healthcare expenditure. Urban-rural inequalities in health outcomes have been demonstrated. Issues around geographical patterning of the association between time-to-death and expenditure remain under-researched. It is unknown whether differences in outcomes translate into differences in costs at the end of life. METHODS: we used a large representative sample of the Scottish population obtained from death records linked to acute inpatient care episodes. We performed retrospective analyses of costs and recorded the most frequent reasons for the last hospital admission. Using a two-part model, we estimated the probability of healthcare utilisation and costs for those patients who incurred positive costs. RESULTS: effects of geography on costs were similar across diagnoses. We did not observe a clear gradient for costs, which were lower in other urban areas compared with large urban areas. Patients from remote and very remote areas incurred higher costs than patients from large, urban areas. The main driver of increased costs was increased length of stay. CONCLUSIONS: our results provide evidence of additional costs associated with remote locations. If length of stay and costs are to be reduced, alternative care provision is required in rural areas. Lower costs in other urban areas compared with large urban areas may be due to urban centres incurring higher costs through case-mix and clinical practice. If inequalities are driven by hospital admission, for an end of life scenario, care delivered closer to home or home-based care seems intuitively attractive and potentially cost-saving.

Cost-Effectiveness of HBV and HCV Screening Strategies--A Systematic Review of Existing Modelling Techniques.

INTRODUCTION: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. METHODS: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. RESULTS: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. CONCLUSION: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers.

Hospital expenditure at the end-of-life: what are the impacts of health status and health risks?

BACKGROUND: It is important for health policy and expenditure projections to understand the relationship between age, death and expenditure on health care (HC). Research has shown that older age groups incur lower hospital costs than previously anticipated and that remaining time to death (TTD) was a much stronger indicator for expenditure than age. How health behaviour or risk factors impact on HC utilisation and costs at the end of life is relatively unknown. Smoking and Body Mass Index (BMI) have featured most prominently and mixed findings exist as to the exact nature of this association. METHODS: This paper considers the relationship between TTD, age and expenditure for inpatient care in the last 12 quarters of life; and introduces measures of health status and risks. A longitudinal dataset covering 35 years is utilised, including baseline survey data linked to hospital and death records. The effect of age, TTD and health indicators on expenditure for inpatient care is estimated using a two-part model. RESULTS: As individuals approach death costs increase. This effect is highly significant (p<0.01) from the last until the 8th quarter before death and influenced by age. Statistically significant effects on costs were found for: smoking status, systolic blood pressure and lung function (FEV1). On average, smokers incurred lower quarterly costs in their last 12 quarters of life than non-smokers (~7%). Participants' BMI at baseline did show a negative association with probability of HC utilisation however this effect disappeared when costs were estimated. CONCLUSIONS: Health risk measures obtained at baseline provide a good indication of individuals' probability of needing medical attention later in life and incurring costs, despite the small size of the effect. Utilising a linked dataset, where such measures are available can add substantially to our ability to explain the relationship between TTD and costs.