Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis.

BACKGROUND: More than 40% of patients awaiting a kidney transplant in the UK are sensitised with human leucocyte antigen (HLA) antibodies. Median time to transplantation for such patients is double that of unsensitised patients at about 74 months. Removing antibody to perform an HLA-incompatible (HLAi) living donor transplantation is perceived to be high risk, although patient survival data are limited. We compared survival of patients opting for an HLAi kidney transplant with that of similarly sensitised patients awaiting a compatible organ. METHODS: From the UK adult kidney transplant waiting list, we selected crossmatch positive living donor HLAi kidney transplant recipients who received their transplant between Jan 1, 2007, and Dec 31, 2013, and were followed up to Dec 31, 2014 (end of study). These patients were matched in a 1:4 ratio with similarly sensitised patients cases listed for a deceased-donor transplant during that period. Data were censored both at the time of transplantation (listed only), and at the end of the study period (listed or transplant). We used Kaplan-Meier curves to compare patient survival between HLAi and the matched cohort. FINDINGS: Of 25 518 patient listings, 213 (1%) underwent HLAi transplantation during the study period. 852 matched controls were identified, of whom 41% (95% CI 32-50) remained without a transplant at 58 months after matching. We noted no difference in survival between patients who were in the HLAi group compared with the listed only group (log rank p=0·446), or listed or transplant group (log rank p=0·984). INTERPRETATION: Survival of sensitised patients undergoing HLAi in the UK is comparable with those on dialysis awaiting a compatible organ, many of whom are unlikely to be have a transplant. Choosing a direct HLAi transplant has no detrimental effect on survival, but offers no survival benefit, by contrast with similar patients studied in a North American multicentre cohort. FUNDING: UK National Health Service Blood & Transplant and Guy's & St Thomas' National Institute for Health Research Biomedical Research Centre.

The economic cost of treatment-resistant depression in patients referred to a specialist service.

BACKGROUND: Patients with treatment-resistant depression (TRD) suffer very significant morbidity and are at a disadvantage concerning optimal clinical management. There are high associated societal costs. AIMS: A detailed analysis of health economic costs in the United Kingdom in a group manifesting a severe form of TRD in the 12 months before their participation in a major randomized controlled treatment trial. METHODS: The sample consisted of 118 participants from the Tavistock Adult Depression Study. Recruitment was from primary care on the basis of current major depression disorder of at least 2 years' duration and two failed treatment attempts. Service utilization was assessed based on self-report and general practitioner (GP) medical records. Generalized linear models were used to identify predictors of cost. RESULTS: All participants used GP services. Use of other doctors and practice nurses was also high. The mean total societal cost was £22 124, 80% of which was due to lost work and care required of families. Level of general functioning was found to be the most consistent predictor of costs. CONCLUSIONS: Severe forms of TRD are associated with high costs in which unpaid care and lost work predominate. Treatments that improve functioning may reduce the large degree of burden.

Clinical outcomes and costs for people with complex psychosis; a naturalistic prospective cohort study of mental health rehabilitation service users in England.

BACKGROUND: Mental health rehabilitation services in England focus on people with complex psychosis. This group tend to have lengthy hospital admissions due to the severity of their problems and, despite representing only 10-20 % of all those with psychosis, they absorb 25-50 % of the total mental health budget. Few studies have investigated the effectiveness of these services and there is little evidence available to guide clinicians working in this area. As part of a programme of research into inpatient mental health rehabilitation services, we carried out a prospective study to investigate longitudinal outcomes and costs for patients of these services and the predictors of better outcome. METHOD: Inpatient mental health rehabilitation services across England that scored above average (median) on a standardised quality assessment tool used in a previous national survey were eligible for the study. Unit quality was reassessed and costs of care and patient characteristics rated using standardised tools at recruitment. Multivariable regression modelling was used to investigate the relationship between service quality, patient characteristics and the following clinical outcomes at 12 month follow-up: social function; length of admission in the rehabiliation unit; successful community discharge (without readmission or community placement breakdown) and costs of care. RESULTS: Across England, 50 units participated and 329 patients were followed over 12 months (94 % of those recruited). Service quality was not associated with patients' social function or length of admission (median 16 months) at 12 months but most patients were successfully discharged (56 %) or ready for discharge (14 %), with associated reductions in the costs of care. Factors associated with successful discharge were the recovery orientation of the service (OR 1.04, 95 % CI 1.00-1.08), and patients' activity (OR 1.03, 95 % CI 1.01-1.05) and social skills (OR 1.13, 95 % CI 1.04-1.24) at recruitment. CONCLUSION: Inpatient mental health rehabilitation services in England are able to successfully discharge over half their patients within 18 months, reducing the costs of care for this complex group. Provision of recovery orientated practice that promotes patients' social skills and activities may further enhance the effectiveness of these services.

Study protocol: cluster randomised controlled trial to assess the clinical and cost effectiveness of a staff training intervention in inpatient mental health rehabilitation units in increasing service users' engagement in activities.

BACKGROUND: This study focuses on people with complex and severe mental health problems who require inpatient rehabilitation. The majority have a diagnosis of schizophrenia whose recovery has been delayed due to non-response to first-line treatments, cognitive impairment, negative symptoms and co-existing problems such as substance misuse. These problems contribute to major impairments in social and everyday functioning necessitating lengthy admissions and high support needs on discharge to the community. Engagement in structured activities reduces negative symptoms of psychosis and may lead to improvement in function, but no trials have been conducted to test the efficacy of interventions that aim to achieve this. METHODS/DESIGN: This study aims to investigate the clinical and cost-effectiveness of a staff training intervention to increase service users' engagement in activities. This is a single-blind, two-arm cluster randomised controlled trial involving 40 inpatient mental health rehabilitation units across England. Units are randomised on an equal basis to receive either standard care or a "hands-on", manualised staff training programme comprising three distinct phases (predisposing, enabling and reinforcing) delivered by a small team of psychiatrists, occupational therapists, service users and activity workers. The primary outcome is service user engagement in activities 12 months after randomisation, assessed using a standardised measure. Secondary outcomes include social functioning and costs and cost-effectiveness of care. DISCUSSION: The study will provide much needed evidence for a practical staff training intervention that has potential to improve service user functioning, reducing the need for hospital treatment and supporting successful community discharge. The trial is registered with Current Controlled Trials (Ref ISRCTN25898179).

Cost-effectiveness of long-term psychoanalytic psychotherapy for treatment-resistant depression: RCT evidence from the Tavistock Adult Depression Study (TADS).

BACKGROUND: Treatment-resistant depression (TRD) accounts for a large fraction of the burden of depression. The interventions currently used are mostly pharmacological and short-term psychotherapies, but their effectiveness is limited. The Tavistock Adult Depression Study found evidence for the effectiveness of long-term psychoanalytic psychotherapy (LTPP) plus treatment as usual (TAU), versus TAU alone, for TRD. Even after a 2-year follow-up, moderate effect sizes were sustained. This study assessed the cost-effectiveness of this LTPP + TAU. METHODS: We conducted a within-trial economic evaluation using a Bayesian framework. RESULTS: Quality-adjusted life years (QALYs) were 0.16 higher in the LTPP + TAU group compared with TAU. The direct cost of LTPP was £5500, with no substantial compensating savings elsewhere. Overall, average health and social care costs in the LTPP + TAU group were £5000 more than in the TAU group, employment rates were unchanged, and effects on other non-healthcare costs were uncertain. Accordingly, the incremental cost-effectiveness ratio was ≈£33,000/QALY; the probability that LTPP + TAU was cost-effective at a willingness to pay of £20,000/QALY was 18 %. LIMITATIONS: The sample size of this study was relatively small, and the fraction of missing service-use data was approximately 50 % at all time points. The study was conducted at a single site, potentially reducing generalizability. CONCLUSIONS: Although LTPP + TAU was found to be clinically effective for treating TRD, it was not found to be cost-effective compared with TAU. However, given the sustained effects over the follow-up period it is likely that the time horizon of this study was too short to capture all benefits of LTPP augmentation.

Cost-effectiveness of care for people with psychosis in the community and psychiatric hospitals in the Czech Republic: an economic analysis.

BACKGROUND: The absence of economic evidence hinders current reforms of hospital-based mental health systems in central and eastern Europe. We aimed to assess the cost-effectiveness of discharge to community care for people with chronic psychoses compared with care in psychiatric hospitals in the Czech Republic. METHODS: We did a prospective study of people aged 18-64 years with chronic psychotic disorders in the Czech Republic who had been discharged into community services or were receiving inpatient psychiatric care for at least 3 months at baseline. We measured health-related quality of life with the EuroQol five-dimension five-level questionnaire. Adjusting for baseline differences between the two groups, we assessed differences in societal costs in 2016 and quality-adjusted life-years (QALYs) during a 12-month follow-up, which we then used to estimate the incremental cost-effectiveness ratio (ICER). We did multiple sensitivity analyses to assess the robustness of our results. FINDINGS: In our baseline case scenario, we included 115 patients who were either community service users (n=35) or inpatients (n=80) at baseline. The two groups were similar in terms of baseline characteristics. The annual QALY was 0·77 in patients receiving community care at baseline compared with 0·80 in patients in hospital at baseline (difference 0·03, 95% CI -0·04 to 0·10), but the costs of discharge to the community were €8503 compared with €16 425 for no discharge (difference €7922, 95% CI 4497-11 346), such that the ICER reached more than €250 000 per QALY. This ICER is substantially higher than levels that are conventionally considered to be cost-effective and the estimated probability that discharge to the community was cost-effective was very high (≥97%). None of the sensitivity analyses changed these results qualitatively. INTERPRETATION: This study provides economic evidence for deinstitutionalisation by showing that discharge to community care is cost-effective compared with care in psychiatric hospitals in the Czech Republic. These findings add to the human rights and clinical-based arguments for mental health-care reforms in central and eastern Europe. FUNDING: Ministry of Education, Youth and Sports of the Czech Republic; EEA and Norway Grants.

Evaluating the economic impact of screening and treatment for depression in the workplace.

Depression is the most common psychiatric illness and cause of disability, and associated with durable impacts on productivity and represents one of the major causes of workplace absenteeism and presenteeism. Few studies, however, examine the economic impact of treatment of depression in the workplace, particularly from the perspective of the employer. We estimated the relative cost-effectiveness of treatment for employees with depression in the workplace. We used a decision-analytic model to estimate the relative cost-effectiveness of (i) psychotherapy, (ii) pharmacotherapy and (iii) combination of psychotherapy and pharmacotherapy and whether they reduce sickness, absenteeism and presenteeism for people with depression. Costs and savings to the employer were also estimated, and policy recommendations made about how best to translate this evidence into practice. Both pharmacotherapy treatment and psychotherapy treatment were found to be cost-saving from the perspective of the employer. Psychotherapy was found to be the most cost-effective option with an incremental cost-effectiveness ratio of €22,225. This study provides evidence that screening and treatment for depression in the workplace is cost-effective and represents a worthwhile investment from the business perspective.

Utility of the Health of the Nation Outcome Scales (HoNOS) in Predicting Mental Health Service Costs for Patients with Common Mental Health Problems: Historical Cohort Study.

BACKGROUND: Few countries have made much progress in implementing transparent and efficient systems for the allocation of mental health care resources. In England there are ongoing efforts by the National Health Service (NHS) to develop mental health 'payment by results' (PbR). The system depends on the ability of patient 'clusters' derived from the Health of the Nation Outcome Scales (HoNOS) to predict costs. We therefore investigated the associations of individual HoNOS items and the Total HoNOS score at baseline with mental health service costs at one year follow-up. METHODS: An historical cohort study using secondary care patient records from the UK financial year 2012-2013. Included were 1,343 patients with 'common mental health problems', represented by ICD-10 disorders between F32-48. Costs were based on patient contacts with community-based and hospital-based mental health services. The costs outcome was transformed into 'high costs' vs 'regular costs' in main analyses. RESULTS: After adjustment for covariates, 11 HoNOS items were not associated with costs. The exception was 'self-injury' with an odds ratio of 1.41 (95% CI 1.10-2.99). Population attributable fractions (PAFs) for the contribution of HoNOS items to high costs ranged from 0.6% (physical illness) to 22.4% (self-injury). After adjustment, the Total HoNOS score was not associated with costs (OR 1.03, 95% CI 0.99-1.07). However, the PAF (33.3%) demonstrated that it might account for a modest proportion of the incidence of high costs. CONCLUSIONS: Our findings provide limited support for the utility of the self-injury item and Total HoNOS score in predicting costs. However, the absence of associations for the remaining HoNOS items indicates that current PbR clusters have minimal ability to predict costs, so potentially contributing to a misallocation of NHS resources across England. The findings may inform the development of mental health payment systems internationally, especially since the vast majority of countries have not progressed past the early stages of this development. Discrepancies between our findings with those from Australia and New Zealand point to the need for further international investigations.

Clinical effectiveness of a staff training intervention in mental health inpatient rehabilitation units designed to increase patients' engagement in activities (the Rehabilitation Effectiveness for Activities for Life [REAL] study): single-blind, cluster-randomised controlled trial.

BACKGROUND: Mental health inpatient rehabilitation services focus on people with complex psychosis who have, for example, treatment-refractory symptoms, cognitive impairment, and severe negative symptoms, which impair functioning and require lengthy admission. Engagement in activities could lead to improvement in negative symptoms and function, but few trials have been done. We aimed to investigate the effectiveness of a staff training intervention to increase patients' engagement in activities. METHODS: We did a single-blind, two-arm, cluster-randomised controlled trial in 40 mental health inpatient rehabilitation units across England. Units were randomly allocated to either a manual-based staff training programme delivered by a small intervention team (intervention group, n=20) or standard care (control group, n=20). The primary outcome was patients' engagement in activities 12 months after randomisation, measured with the time use diary. With this measure, both the degree of engagement in an activity and its complexity are recorded four times a day for a week, rated on a scale of 0-4 for every period (maximum score of 112). Analysis was by intention-to-treat. Random-effects models were used to compare outcomes between study groups. Cost-effectiveness was assessed by combining service costs with the primary outcome. This study is registered with Current Controlled Trials (ISRCTN25898179). FINDINGS: Patients' engagement in activities did not differ between study groups (coefficient 1·44, 95% CI -1·35 to 4·24). An extra £101 was needed to achieve a 1% increase in patients' engagement in activities with the study intervention. INTERPRETATION: Our training intervention did not increase patients' engagement in activities after 12 months of follow-up. This failure could be attributable to inadequate implementation of the intervention, a high turnover of patients in the intervention units, competing priorities on staff time, high levels of patients' morbidity, and ceiling effects because of the high quality of standard care delivered. Further studies are needed to identify interventions that can improve outcomes for people with severe and complex psychosis. FUNDING: National Institute for Health Research.

Cost-effectiveness of natalizumab in multiple sclerosis: an updated systematic review.

As natalizumab (Tysabri; Elan Pharmaceuticals, Inc., Dublin, Ireland) and other disease-modifying drugs are entering the market for multiple sclerosis, the treatment repertoire is expanding beyond the established first-line treatments. This is creating new opportunities but also increasing the uncertainty in the appropriate management of this condition with its considerable societal burden. As a result, economic evaluations are increasingly influential in healthcare decision making. Seven evaluations that included natalizumab have been published to date. They largely report favorable results for this treatment compared with other drugs. However, the models used to reach these conclusions have been subjected to significant debate, owing to limited data availability as well as the methodological complexities and uncertainties in the pharmacoeconomics of multiple sclerosis. This review critically discusses the available evidence based on the cost-effectiveness of natalizumab and uses the data to explain more general issues in the evaluation of similar drugs. The review also suggests how shortcomings in current studies may potentially be addressed in the future.

Economic evaluation of audio based resilience training for depression in primary care.

BACKGROUND: Although there is some evidence on the effectiveness and cost-effectiveness of computerised cognitive behavioural therapy (CCBT) for treating anxiety and depression in primary care, alternative low-cost psychosocial interventions have not been investigated. METHODS: The cost-effectiveness of an audio based resilience training (Positive Mental Training, PosMT) was examined using a decision model. Patient level cost and effectiveness data from a trial comparing a CCBT treatment and usual care and effectiveness data from a study on PosMT were used to inform this. RESULTS: Net benefits of CCBT and PosMT were approximately equal in individuals with 'moderate' depression at baseline and markedly in favour of PosMT for the 'severe' depression subgroup. With only four observations in the 'mild' depression category for PosMT, the existing evidence base remains unaltered. LIMITATIONS: Efficacy data for the PosMT arm was derived from a study using a partially randomised preference design and the model structure contains simplifications due to lack of data availability. CONCLUSION: PosMT may represent good value for money in treatment of depression for certain groups of patients. More research in this area may be warranted.