Navigating the future of Alzheimer's care in Ireland - a service model for disease-modifying therapies in small and medium-sized healthcare systems.

BACKGROUND: A new class of antibody-based drug therapy with the potential for disease modification is now available for Alzheimer's disease (AD). However, the complexity of drug eligibility, administration, cost, and safety of such disease modifying therapies (DMTs) necessitates adopting new treatment and care pathways. A working group was convened in Ireland to consider the implications of, and health system readiness for, DMTs for AD, and to describe a service model for the detection, diagnosis, and management of early AD in the Irish context, providing a template for similar small-medium sized healthcare systems. METHODS: A series of facilitated workshops with a multidisciplinary working group, including Patient and Public Involvement (PPI) members, were undertaken. This informed a series of recommendations for the implementation of new DMTs using an evidence-based conceptual framework for health system readiness based on [1] material resources and structures and [2] human and institutional relationships, values, and norms. RESULTS: We describe a hub-and-spoke model, which utilises the existing dementia care ecosystem as outlined in Ireland's Model of Care for Dementia, with Regional Specialist Memory Services (RSMS) acting as central hubs and Memory Assessment and Support Services (MASS) functioning as spokes for less central areas. We provide criteria for DMT referral, eligibility, administration, and ongoing monitoring. CONCLUSIONS: Healthcare systems worldwide are acknowledging the need for advanced clinical pathways for AD, driven by better diagnostics and the emergence of DMTs. Despite facing significant challenges in integrating DMTs into existing care models, the potential for overcoming challenges exists through increased funding, resources, and the development of a structured national treatment network, as proposed in Ireland's Model of Care for Dementia. This approach offers a replicable blueprint for other healthcare systems with similar scale and complexity.

Geriatric assessment for older people with cancer: policy recommendations.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.

Cost-effectiveness of clinical interventions for delirium: A systematic literature review of economic evaluations.

OBJECTIVE: Little is known about the economic value of clinical interventions for delirium. This review aims to synthesise and appraise available economic evidence, including resource use, costs, and cost-effectiveness of interventions for reducing, preventing, and treating delirium. METHODS: Systematic review of published and grey literature on full and partial economic evaluations. Study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: Fourteen economic evaluations (43% full, 57% partial) across nine multicomponent and nonpharmacological intervention types met inclusion criteria. The intervention costs ranged between US$386 and $553 per person in inpatient settings. Multicomponent delirium prevention intervention and the Hospital Elder Life Program (HELP) reported statistically significant cost savings or cost offsets somewhere else in the health system. Cost savings related to inpatient, outpatient, and out-of-pocket costs ranged between $194 and $6022 per person. The average CHEERS score was 74% (±SD 10%). CONCLUSION: Evidence on a joint distribution of costs and outcomes of delirium interventions was limited, varied and of generally low quality. Directed expansion of health economics towards the evaluation of delirium care is necessary to ensure effective implementation that meets patients' needs and is cost-effective in achieving similar or better outcomes for the same or lower cost.

Value of Nonpharmacological Interventions for People With an Acquired Brain Injury: A Systematic Review of Economic Evaluations.

OBJECTIVES: Acquired brain injury (ABI) has long-lasting effects, and patients and their families require continued care and support, often for the rest of their lives. For many individuals living with an ABI disorder, nonpharmacological rehabilitation treatment care has become increasingly important care component and relevant for informed healthcare decision making. Our study aimed to appraise economic evidence on the cost-effectiveness of nonpharmacological interventions for individuals living with an ABI. METHODS: This systematic review was registered in PROSPERO (CRD42020187469), and a protocol article was subject to peer review. Searches were conducted across several databases for articles published from inception to 2021. Study quality was assessed according the Consolidated Health Economic Evaluation Reporting Standards checklist and Population, Intervention, Control, and Outcomes criteria. RESULTS: Of the 3772 articles reviewed 41 publications met the inclusion criteria. There was a considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives and comparators used. Keeping these issues in mind, we find that 4 multidisciplinary interventions studies concluded that fast-track specialized services were cheaper and more cost-effective than usual care, with cost savings ranging from £253 to £6063. In 3 neuropsychological studies, findings suggested that meditated therapy was more effective and saved money than usual care. In 4 early supported discharge studies, interventions were dominant over usual care, with cost savings ranging from £142 to £1760. CONCLUSIONS: The cost-effectiveness evidence of different nonpharmacological rehabilitation treatments is scant. More robust evidence is needed to determine the value of these and other interventions across the ABI care pathway.

Healthcare costs of dementia diseases before, during and after diagnosis: Longitudinal analysis of 17 years of Swedish register data.

INTRODUCTION: This study examines health-care costs attributed to dementia diseases in the 10 years prior to, during, and 6 years after diagnosis. METHODS: Using administrative register data for people diagnosed with dementia (2010-2016) in southern Sweden (n = 21,184), and a comparison group without dementia, health-care costs over 17 years were examined using longitudinal regression analysis. RESULTS: Average annual health-care costs per person were consistently higher before diagnosis in the dementia group (10 years before: Swedish krona (SEK) 2063, P < .005 and 1 year before: SEK8166, P < .005). At diagnosis, health-care costs were more than twice as high (SEK44,410, P < .005). Four to 6 years after diagnosis, there was no significant different in costs compared to comparators. DISCUSSION: Excess health-care cost arise as early as 10 years before a formal diagnosis of dementia, and while there is a spike in cost after diagnosis, health-care costs are no different 4 years after. These findings question currently accepted assumptions on costs of dementia.

Impact of assessment and intervention by a health and social care professional team in the emergency department on the quality, safety, and clinical effectiveness of care for older adults: A randomised controlled trial.

BACKGROUND: Older adults frequently attend the emergency department (ED) and experience high rates of adverse events following ED presentation. This randomised controlled trial evaluated the impact of early assessment and intervention by a dedicated team of health and social care professionals (HSCPs) in the ED on the quality, safety, and clinical effectiveness of care of older adults in the ED. METHODS AND FINDINGS: This single-site randomised controlled trial included a sample of 353 patients aged ≥65 years (mean age = 79.6, SD = 7.01; 59.2% female) who presented with lower urgency complaints to the ED a university hospital in the Mid-West region of Ireland, during HSCP operational hours. The intervention consisted of early assessment and intervention carried out by a HSCP team comprising a senior medical social worker, senior occupational therapist, and senior physiotherapist. The primary outcome was ED length of stay. Secondary outcomes included rates of hospital admissions from the ED; hospital length of stay for admitted patients; patient satisfaction with index visit; ED revisits, mortality, nursing home admission, and unscheduled hospital admission at 30-day and 6-month follow-up; and patient functional status and quality of life (at index visit and follow-up). Demographic information included the patient's gender, age, marital status, residential status, mode of arrival to the ED, source of referral, index complaint, triage category, falls, and hospitalisation history. Participants in the intervention group (n = 176) experienced a significantly shorter ED stay than the control group (n = 177) (6.4 versus 12.1 median hours, p < 0.001). Other significant differences (intervention versus control) included lower rates of hospital admissions from the ED (19.3% versus 55.9%, p < 0.001), higher levels of satisfaction with the ED visit (p = 0.008), better function at 30-day (p = 0.01) and 6-month follow-up (p = 0.03), better mobility (p = 0.02 at 30 days), and better self-care (p = 0.03 at 30 days; p = 0.009 at 6 months). No differences at follow-up were observed in terms of ED re-presentation or hospital admission. Study limitations include the inability to blind patients or ED staff to allocation due to the nature of the intervention, and a focus on early assessment and intervention in the ED rather than care integration following discharge. CONCLUSIONS: Early assessment and intervention by a dedicated ED-based HSCP team reduced ED length of stay and the risk of hospital admissions among older adults, as well as improving patient satisfaction. Our findings support the effectiveness of an interdisciplinary model of care for key ED outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03739515; registered on 12 November 2018.

The Role of Prevention in Reducing the Economic Impact of ME/CFS in Europe: A Report from the Socioeconomics Working Group of the European Network on ME/CFS (EUROMENE).

This report addresses the extent to which there may be scope for preventive programmes for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and, if so, what economic benefits may accrue from the implementation of such programmes. We consider the economic case for prevention programmes, whether there is scope for preventive programmes for ME/CFS, and what are the health and economic benefits to be derived from the implementation of such programmes. We conclude that there is little scope for primary prevention programmes, given that ME/CFS is attributable to a combination of host and environmental risk factors, with host factors appearing to be most prominent, and that there are few identified modifiable risk factors that could be the focus of such programmes. The exception is in the use of agricultural chemicals, particularly organophosphates, where there is scope for intervention, and where Europe-wide programmes of health education to encourage safe use would be beneficial. There is a need for more research on risk factors for ME/CFS to establish a basis for the development of primary prevention programmes, particularly in respect of occupational risk factors. Secondary prevention offers the greatest scope for intervention, to minimise diagnostic delays associated with prolonged illness, increased severity, and increased costs.

The economic cost of delirium: A systematic review and quality assessment.

INTRODUCTION: This review aims to systematically identify and appraise the methodological quality of claims on the cost of delirium; and discuss challenges and opportunities for improvements in the precision of the estimates. METHODS: Searches of scientific papers and gray literature were performed up until June 2020. The Larg and Moss checklist was used to assess the methodological quality of the included studies. RESULTS: After deduplication, the search identified 317 potentially relevant articles, of which 17 articles were eligible for inclusion. After adjusting for inflation and common currency, the cost of delirium ranged between $806 and $24,509 (in 2019 US$). DISCUSSION: This review found significant variation among the cost estimates and methodological quality. There has been limited focus on dementia as a sequela of delirium in terms of economic implications, but recent evidence suggests cost implications of delirium may be 52% higher when dementia is considered.

A Literature Review of GP Knowledge and Understanding of ME/CFS: A Report from the Socioeconomic Working Group of the European Network on ME/CFS (EUROMENE).

Background and Objectives: The socioeconomic working group of the European myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Research Network (EUROMENE) has conducted a review of the literature pertaining to GPs' knowledge and understanding of ME/CFS; Materials and Methods: A MEDLINE search was carried out. The papers identified were reviewed following the synthesis without meta-analysis (SWiM) methodology, and were classified according to the focus of the enquiry (patients, GPs, database and medical record studies, evaluation of a training programme, and overview papers), and whether they were quantitative or qualitative in nature; Results: Thirty-three papers were identified in the MEDLINE search. The quantitative surveys of GPs demonstrated that a third to a half of all GPs did not accept ME/CFS as a genuine clinical entity and, even when they did, they lacked confidence in diagnosing or managing it. It should be noted, though, that these papers were mostly from the United Kingdom. Patient surveys indicated that a similar proportion of patients was dissatisfied with the primary medical care they had received. These findings were consistent with the findings of the qualitative studies that were examined, and have changed little over several decades; Conclusions: Disbelief and lack of knowledge and understanding of ME/CFS among GPs is widespread, and the resultant diagnostic delays constitute a risk factor for severe and prolonged disease. Failure to diagnose ME/CFS renders problematic attempts to determine its prevalence, and hence its economic impact.

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks.

Cost-effectiveness of brief structured interventions to discontinue long-term benzodiazepine use: an economic analysis alongside a randomised controlled trial.

Background: In Spain, long-term use of benzodiazepine is prevalent in 7% of the population; however, this longer-term use lacks clinical benefits, costs €90million per year and side-effects further add extra cost through adverse health outcomes. This study aims to estimate the cost-effectiveness of primary care services stepped dose reduction of long-term benzodiazepines using either Structured Interview with Follow-up (SIF) or Without Follow-up (SIW), compared to Treatment as Usual (TAU). Design: Cost-effectiveness analysis was conducted alongside randomised control utilizing data from three arm cluster randomized trial. Setting: Primary care. Participants: 75 general practitioners were randomised to one of the three arms (TAU, SIW, SIF). Measurements: Cost and Cost per Quality-Adjusted Life Year (QALY) Results: Compared to usual care, providing SIW per participant costs an additional €117.94 and adding patient follow-up, €218.4. As a result of intervention, participants showed a gain of, on average, for SIW 0.0144 QALY (95% CI -0.0137 to 0.0425) and for SIF 0.0340 QALYs (0.0069 to 0.0612). The Incremental Cost Effectiveness Ratio was €8190.28/QALY (SIW) and €6423.53/QALY (SIF). At the Spanish reimbursement threshold (€45,000 per QALY) the chance interventions are cost effective is 79.8% for SIW and 97.7% for SIF. Conclusions: Brief structured interventions to discontinue long-term benzodiazepine use represent value for money, particularly with scheduled follow-up appointments, and would represent a cost-effective investment by the Spanish healthcare to reduce prevalence of long-term use.

The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE).

We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment. However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries. We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list. We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.

Neuropsychological rehabilitation interventions for people with an acquired brain injury. A protocol for a systematic review of economic evaluation.

Background: New emerging evidence has demonstrated the need for effective interventions to help people living with an acquired brain injury (ABI). Evidence on cost-effectiveness, which can help inform use of limited resources, is scarce in this area and therefore the purpose of this systematic review is to critically appraise and consolidate the current evidence on economic evaluations of ABI rehabilitation interventions. Methods: Systematic review methodology will be applied to identify, select and extract data from published economic evaluation studies (trial-based, non-trial based, simulation-based, decision model and trial-based model economic evaluations) of ABI treatment interventions in adults. A systematic literature search will be conducted on the following electronic databases: EMBASE, Econlit, CINAHL, Medline, Econlit, the National Health Service Economic Evaluation Database and PsyclNFO. This review will only include cost-effectiveness analysis studies (e.g., cost per life year gained), cost-benefit and cost minimisation analyses in which the designs were randomised controlled trials (RCTs), non-RCT studies, cost-utility analyses (e.g., cost per quality-adjusted life year (QALY) gained or cost per disability-adjusted life year averted), cohort studies, and modeling studies. Only studies that were published in English, associated with adults who have an ABI will be included. There will be no restrictions on perspective, sample size, country, follow-up duration or setting. The search strategy terms will include the following: acquired brain injury, brain*; cost*; or cost-benefit analysis*. Following data extraction, a narrative summary and tables will be used to summarize the characteristics and results of included studies. Discussion: The findings from this review will be beneficial to health policy decision makers when examining the evidence of economic evaluations in this field. In addition, it is anticipated that this review will identify gaps in the current economic literature to inform future-related research. Systematic review registration: PROSPERO CRD42020187469 (25 th June 2020).

A randomised controlled trial exploring the impact of a dedicated health and social care professionals team in the emergency department on the quality, safety, clinical and cost-effectiveness of care for older adults: a study protocol.

BACKGROUND: Older people are frequent emergency department (ED) users who present with complex issues that are linked to poorer health outcomes following the index visit, often have increased ED length of stay, and tend to have raised healthcare costs. Encouraging evidence suggests that ED teams involving health and social care professionals (HSCPs) can contribute to enhanced patient flow and an improved patient experience by improving care decision-making and thus promoting timely and effective care. However, the evidence supporting the impact of HSCP teams assessing and intervening with older adults in the ED is limited and identifies important methodological limitations, highlighting the need for more robust and comprehensive investigations of this model of care. This study aims to evaluate the impact of a dedicated ED-based HSCP team on the quality, safety, and clinical- and cost-effectiveness of care of older adults when compared with usual care. METHODS: The study is a single-site randomised controlled trial whereby patients aged ≥65 years who present to the ED of a large Irish hospital will be randomised to the experimental group (ED-based HSCP assessment and intervention) or the control group (usual ED care). The recruitment target is 320 participants. The HSCP team will provide a comprehensive functional assessment as well as interventions to promote a safe discharge for the patient. The primary outcome is ED length of stay (from arrival to discharge). Secondary outcomes include: rates of hospital admissions from the ED, ED re-visits, unplanned hospital admissions and healthcare utilisation at 30 days, and 4 and 6 months of follow-up; patient functional status and quality of life (at baseline and follow-up); patient satisfaction; cost-effectiveness in terms of costs associated with ED-based HSCP compared with usual care; and perceptions on implementation by ED staff members. DISCUSSION: This is the first randomised controlled trial testing the impact of HSCPs working in teams in the ED on the quality, safety, and clinical- and cost-effectiveness of care for older patients. The findings of this study will provide important information on the effectiveness of this model of care for future implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03739515 . Registered on 12 November 2018.

Randomised controlled trial and economic evaluation of a task-based weight management group programme.

BACKGROUND: Obesity is a rising global threat to health and a major contributor to health inequalities. Weight management programmes that are effective, economical and reach underprivileged groups are needed. We examined whether a multi-modal group intervention structured to cater for clients from disadvantaged communities (Weight Action Programme; WAP) has better one-year outcomes than a primary care standard weight management intervention delivered by practice nurses (PNI). METHODS: In this randomised controlled trial, 330 obese adults were recruited from general practices in London and allocated (2:1) to WAP (N = 221) delivered over eight weekly group sessions or PNI (N = 109) who received four sessions over eight weeks. Both interventions covered diet, physical activity and self-monitoring. The primary outcome was the change in weight from baseline at 12 months. To indicate value to the NHS, a cost effectiveness analysis estimated group differences in cost and Quality-Adjusted Life-Years (QALYs) related to WAP. RESULTS: Participants were recruited from September 2012 to January 2014 with follow-up completed in February 2015. Most participants were not in paid employment and 60% were from ethnic minorities. 88% of participants in each study arm provided at least one recorded outcome and were included in the primary analysis. Compared with the PNI, WAP was associated with greater weight loss overall (- 4·2 kg vs. - 2·3 kg; difference = - 1·9 kg, 95% CI: -3·7 to - 0·1; P = 0·04) and was more likely to generate a weight loss of at least 5% at 12 months (41% vs. 27%, OR = 14·61 95% CI: 2·32 to 91·96, P = 0·004). With an incremental cost-effectiveness ratio (ICER) of £7742/QALY, WAP would be considered highly cost effective compared to PNI. CONCLUSIONS: The task-based programme evaluated in this study can provide a template for an effective and economical approach to weight management that can reach clients from disadvantaged communities. TRIAL REGISTRATION: ISRCTN ISRCTN45820471 . Registered 12/10/2012 (retrospectively registered).

CollAborative care for Screen-Positive EldeRs with major depression (CASPER plus): a multicentred randomised controlled trial of clinical effectiveness and cost-effectiveness.

BACKGROUND: Depression in older adults is common and is associated with poor quality of life, increased morbidity and early mortality, and increased health and social care use. Collaborative care, a low-intensity intervention for depression that is shown to be effective in working-age adults, has not yet been evaluated in older people with depression who are managed in UK primary care. The CollAborative care for Screen-Positive EldeRs (CASPER) plus trial fills the evidence gap identified by the most recent guidelines on depression management. OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of collaborative care for older adults with major depressive disorder in primary care. DESIGN: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with embedded qualitative study. Participants were automatically randomised by computer, by the York Trials Unit Randomisation Service, on a 1 : 1 basis using simple unstratified randomisation after informed consent and baseline measures were collected. Blinding was not possible. SETTING: Sixty-nine general practices in the north of England. PARTICIPANTS: A total of 485 participants aged ≥ 65 years with major depressive disorder. INTERVENTIONS: A low-intensity intervention of collaborative care, including behavioural activation, delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual general practitioner (GP) care. The control arm received only usual GP care. MAIN OUTCOME MEASURES: The primary outcome measure was Patient Health Questionnaire-9 items score at 4 months post randomisation. Secondary outcome measures included depression severity and caseness at 12 and 18 months, the EuroQol-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder-7 items, Connor-Davidson Resilience Scale-2 items, a medication questionnaire, objective data and adverse events. Participants were followed up at 12 and 18 months. RESULTS: In total, 485 participants were randomised (collaborative care, n = 249; usual care, n = 236), with 390 participants (80%: collaborative care, 75%; usual care, 86%) followed up at 4 months, 358 participants (74%: collaborative care, 70%; usual care, 78%) followed up at 12 months and 344 participants (71%: collaborative care, 67%; usual care, 75%) followed up at 18 months. A total of 415 participants were included in primary analysis (collaborative care, n = 198; usual care, n = 217), which revealed a statistically significant effect in favour of collaborative care at the primary end point at 4 months [8.98 vs. 10.90 score points, mean difference 1.92 score points, 95% confidence interval (CI) 0.85 to 2.99 score points; p < 0.001], equivalent to a standard effect size of 0.34. However, treatment differences were not maintained in the longer term (at 12 months: 0.19 score points, 95% CI -0.92 to 1.29 score points; p = 0.741; at 18 months: < 0.01 score points, 95% CI -1.12 to 1.12 score points; p = 0.997). The study recorded details of all serious adverse events (SAEs), which consisted of 'unscheduled hospitalisation', 'other medically important condition' and 'death'. No SAEs were related to the intervention. Collaborative care showed a small but non-significant increase in quality-adjusted life-years (QALYs) over the 18-month period, with a higher cost. Overall, the mean cost per incremental QALY for collaborative care compared with usual care was £26,016; however, for participants attending six or more sessions, collaborative care appears to represent better value for money (£9876/QALY). LIMITATIONS: Study limitations are identified at different stages: design (blinding unfeasible, potential contamination), process (relatively low overall consent rate, differential attrition/retention rates) and analysis (no baseline health-care resource cost or secondary/social care data). CONCLUSION: Collaborative care was effective for older people with case-level depression across a range of outcomes in the short term though the reduction in depression severity was not maintained over the longer term of 12 or 18 months. Participants who received six or more sessions of collaborative care did benefit substantially more than those who received fewer treatment sessions but this difference was not statistically significant. FUTURE WORK RECOMMENDATIONS: Recommendations for future research include investigating the longer-term effect of the intervention. Depression is a recurrent disorder and it would be useful to assess its impact on relapse and the prevention of future case-level depression. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45842879. 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. 21, No. 67. See the NIHR Journals Library website for further project information.

CollAborative care and active surveillance for Screen-Positive EldeRs with subthreshold depression (CASPER): a multicentred randomised controlled trial of clinical effectiveness and cost-effectiveness.

BACKGROUND: Efforts to reduce the burden of illness and personal suffering associated with depression in older adults have focused on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/subthreshold depression, but these patients also suffer significant impairments in their quality of life and level of functioning. There is currently no clear evidence-based guidance regarding treatment for this patient group. OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of a low-intensity intervention of collaborative care for primary care older adults who screened positive for subthreshold depression. DESIGN: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. SETTING: Thirty-two general practitioner (GP) practices in the north of England. PARTICIPANTS: A total of 705 participants aged ≥ 75 years during the pilot phase and ≥ 65 years during the main trial with subthreshold depression. INTERVENTIONS: Participants in the intervention group received a low-intensity intervention of collaborative care, which included behavioural activation delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual GP care. Control-arm participants received only usual GP care. MAIN OUTCOME MEASURES: The primary outcome measure was a self-reported measure of depression severity, the Patient Health Questionnaire-9 items PHQ-9 score at 4 months post randomisation. Secondary outcome measures included the European Quality of Life-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder seven-item scale, Connor-Davidson Resilience Scale two-item version, a medication questionnaire and objective data. Participants were followed up for 12 months. RESULTS: In total, 705 participants were randomised (collaborative care n = 344, usual care n = 361), with 586 participants (83%; collaborative care 76%, usual care 90%) followed up at 4 months and 519 participants (74%; collaborative care 68%, usual care 79%) followed up at 12 months. Attrition was markedly greater in the collaborative care arm. Model estimates at the primary end point of 4 months revealed a statistically significant effect in favour of collaborative care compared with usual care [mean difference 1.31 score points, 95% confidence interval (CI) 0.67 to 1.95 score points; p < 0.001]. The difference equates to a standard effect size of 0.30, for which the trial was powered. Treatment differences measured by the PHQ-9 were maintained at 12 months' follow-up (mean difference 1.33 score points, 95% CI 0.55 to 2.10 score points; p = 0.001). Base-case cost-effectiveness analysis found that the incremental cost-effectiveness ratio was £9633 per quality-adjusted life-year (QALY). On average, participants allocated to collaborative care displayed significantly higher QALYs than those allocated to the control group (annual difference in adjusted QALYs of 0.044, 95% bias-corrected CI 0.015 to 0.072; p = 0.003). CONCLUSIONS: Collaborative care has been shown to be clinically effective and cost-effective for older adults with subthreshold depression and to reduce the proportion of people who go on to develop case-level depression at 12 months. This intervention could feasibly be delivered in the NHS at an acceptable cost-benefit ratio. Important future work would include investigating the longer-term effect of collaborative care on the CASPER population, which could be conducted by introducing an extension to follow-up, and investigating the impact of collaborative care on managing multimorbidities in people with subthreshold depression. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02202951. 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. 21, No. 8. See the NIHR Journals Library website for further project information.

Tackling obesity in areas of high social deprivation: clinical effectiveness and cost-effectiveness of a task-based weight management group programme - a randomised controlled trial and economic evaluation.

BACKGROUND: An increasing number of people require help to manage their weight. The NHS recommends weight loss advice by general practitioners and/or a referral to a practice nurse. Although this is helpful for some, more effective approaches that can be disseminated economically on a large scale are needed. OBJECTIVE: To assess whether or not a task-based weight management programme [Weight Action Programme (WAP)] has better long-term effects than a 'best practice' intervention provided in primary care by practice nurses. DESIGN: Randomised controlled trial with cost-effectiveness analysis. SETTING: General practices in east London, UK. PARTICIPANTS: Three hundred and thirty adults with a body mass index (BMI) of ≥ 30 kg/m2 or a BMI of ≥ 28 kg/m2 plus comorbidities were recruited from local general practices and via media publicity. Those who had a BMI of > 45 kg/m2, had lost > 5% of their body weight in the previous 6 months, were currently pregnant or taking psychiatric medications were excluded. Participants were randomised (2 : 1) to the WAP or nurse arms. INTERVENTIONS: The WAP intervention was delivered in eight weekly group sessions that combined dietary and physical activity, advice and self-monitoring in a group-oriented intervention. The initial course was followed by 10 monthly group maintenance sessions open to all participants in this study arm. The practice nurse intervention (best usual care) consisted of four one-to-one sessions delivered over 8 weeks, and included standard advice on diet and physical activity based on NHS 'Change4Life' materials and motivational support. MAIN OUTCOME MEASURES: The primary outcome measure was weight change at 12 months. Secondary outcome measures included change in BMI, waist circumference and blood pressure, and proportion of participants losing at least 5% and 10% of baseline body weight. Staff collecting measurements at the 6- and 12-month follow-ups were blinded to treatment allocation. The primary outcome measure was analysed according to the intention-to-treat principle, and included all participants with at least one recorded outcome at either 1, 2, 6 or 12 months. The analysis employed a mixed-effects linear regression model, adjusted for baseline weight, age, sex, ethnicity, smoking status and general practice. The European Quality of Life-5 Dimensions-5 Levels questionnaire was completed and used to estimate quality-adjusted life-years (QALYs) within the cost-effectiveness analysis. RESULTS: There were 330 participants (WAP arm, n = 221; nurse arm, n = 109; 72% women). A total of 291 (88%) participants (WAP arm, n = 194; nurse arm, n = 97) were included in the main analysis for the primary outcome. Weight loss at 12 months was greater in the WAP arm than in the nurse intervention arm [-4.2 kg vs. -2.3 kg; difference -1.9 kg, 95% confidence interval (CI) -3.7 to -0.1 kg; p = 0.04]. Participants in the WAP arm were more likely than participants in the nurse arm to have lost at least 5% of their baseline body weight at 12 months (41% vs. 27%; odds ratio 14.61, 95% CI 2.32 to 91.96; p = 0.004). The incremental cost-effectiveness ratio for WAP over and above the nurse arm is £7742 per QALY. CONCLUSIONS: A WAP delivered in general practice better promotes weight loss over 12 months than a best usual practice nurse-led weight loss programme. LIMITATIONS: The trial recruited mostly women. Research is needed into factors that would make weight loss programmes more attractive to men. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45820471. 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. 20, No. 79. See the NIHR Journals Library website for further project information.

Are Non-Pharmacological Interventions Effective in Reducing Drug Use and Criminality? A Systematic and Meta-Analytical Review with an Economic Appraisal of These Interventions.

Background: The numbers of incarcerated people suffering from drug dependence has steadily risen since the 1980s and only a small proportion of these receive appropriate treatment. A systematic review to evaluate the effectiveness and economic evidence of non-pharmacological interventions for drug using offenders was conducted. Methods: Cochrane Collaboration criteria were used to identify trials across 14 databases between 2004 and 2014. A series of meta-analyses and an economic appraisal were conducted. Results: 43 trials were identified showing to have limited effect in reducing re-arrests RR 0.97 (95% CI 0.89-1.07) and drug use RR 0.90 (95% CI 0.80-1.00) but were found to significantly reduce re-incarceration RR 0.70 (95% CI 0.57-0.85). Therapeutic community programs were found to significantly reduce the number of re-arrests RR 0.70 (95% CI 0.56-0.87). 10 papers contained economic information. One paper presented a cost-benefit analysis and two reported on the cost and cost effectiveness of the intervention. Conclusions: We suggest that therapeutic community interventions have some benefit in reducing subsequent re-arrest. We recommend that economic evaluations should form part of standard trial protocols.

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

BACKGROUND AND OBJECTIVES: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. CONCLUSIONS: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. LIMITATIONS: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. FUTURE WORK: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. 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. 20, No. 41. See the NIHR Journals Library website for further project information.