Margaret Heslin

Multiple Sclerosis in the UK Service Use, Costs, Quality of Life and Disability

AbstractBackground: Multiple sclerosis (MS) is a chronic condition that affects quality of life (QOL), leads to disability and requires ongoing care inputs. Few studies have examined the impact of QOL, disability and demographic characteristics on treatment costs. Objective: To investigate the links between service use, costs, QOL and disability for people with MS. Methods: A cross-sectional study was conducted in people with MS who were members of the Multiple Sclerosis Society of Great Britain and Northern Ireland. A questionnaire, consisting of sociodemographic questions, the Client Service Receipt Inventory, EQ-5D and Guy’s Neurological Disability Scale (GNDS), was sent to 4000 members of the Society. Service and lost employment costs were calculated. Regression models were developed to identify the participant characteristics that were associated with costs, QOL and disability. All costs are presented in year 2006–7 values. Results: Questionnaires were returned by 1942 members (48.9%). The mean (SD) EQ-5D QOL score was 0.41 (0.34), whilst the GNDS disability score was 20.8 (8.9). The mean (SD) service cost over the preceding 6 months was £8397 (£10 404), and most of this (71.6%) was due to informal care. Only a small amount of cost (8.1%) was due to the use of disease-modifying drugs and drugs for spasticity. Lost employment costs amounted to a mean of £4240. Higher costs were associated with higher levels of disability and lower levels of health-related QOL. Conclusions: This study showed that MS participants had high levels of service use, and that QOL was low in comparison with other conditions. There were significant associations between costs, QOL and disability.

Supported employment: randomised controlled trial

Background There is evidence from North American trials that supported employment using the individual placement and support (IPS) model is effective in helping individuals with severe mental illness gain competitive employment. There have been few trials in other parts of the world. Aims To investigate the effectiveness and cost-effectiveness of IPS in the UK. Method Individuals with severe mental illness in South London were randomised to IPS or local traditional vocational services (treatment as usual) (ISRCTN96677673). Results Two hundred and nineteen participants were randomised, and 90% assessed 1 year later. There were no significant differences between the treatment as usual and intervention groups in obtaining competitive employment (13% in the intervention group and 7% in controls; risk ratio 1.35, 95% CI 0.95–1.93, P = 0.15), nor in secondary outcomes. Conclusions There was no evidence that IPS was of significant benefit in achieving competitive employment for individuals in South London at 1-year follow-up, which may reflect suboptimal implementation. Implementation of IPS can be challenging in the UK context where IPS is not structurally integrated with mental health services, and economic disincentives may lead to lower levels of motivation in individuals with severe mental illness and psychiatric professionals.

Reappraising the Long-term Course and Outcome of Psychotic Disorders: The ÆSOP-10 Study

BACKGROUND Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare. METHOD AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews. RESULTS At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1-4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London. CONCLUSIONS Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

Mortality in Schizophrenia and Other Psychoses: A 10-Year Follow-up of the ӔSOP First-Episode Cohort

The excess mortality in people with psychotic disorders is a major public health concern, but little is known about the clinical and social risk factors which may predict this health inequality and help inform preventative strategies. We aimed to investigate mortality in a large epidemiologically characterized cohort of individuals with first-episode psychosis compared with the general population and to determine clinical and social risk factors for premature death. All 557 individuals with first-episode psychosis initially identified in 2 areas (Southeast London and Nottinghamshire, United Kingdom) were traced over a 10-year period in the ӔSOP-10 study. Compared with the general population, all-cause (standardized mortality ratio [SMR] 3.6, 95% confidence interval [CI] 2.6–4.9), natural-cause (SMR 1.7, 95% CI 1.0–2.7) and unnatural-cause (SMR 13.3, 95% CI 8.7–20.4) mortality was very high. Illicit drug use was associated with an increased risk of all-cause mortality (adj. rate ratio [RR] 2.31, 95% CI 1.06–5.03). Risk of natural-cause mortality increased with a longer time to first remission (adj. RR 6.61, 95% CI 1.33–32.77). Family involvement at first contact strongly reduced risk of unnatural-cause mortality (adj. RR 0.09, 95% CI 0.01–0.69). Our findings suggest that the mortality gap in people with psychotic disorders remains huge and may be wider for unnatural-cause mortality than previously reported. Efforts should now focus on further understanding and targeting these tractable clinical and social risk factors of excess mortality. Early intervention and dual diagnosis services may play a key role in achieving more rapid remission and carer involvement and addressing substance use problems to reduce excess mortality in psychosis.

Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study.

Abstract It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described.

Randomized controlled trial of supported employment in England: 2 year follow-up of the Supported Work and Needs (SWAN) study

Studies from North America have concluded that supported employment using the Individual Placement and Support (IPS) model is effective in helping individuals with severe and persistent mental illness gain competitive employment. The aim of this study was to investigate the effectiveness and cost-effectiveness of IPS in England in patients followed up for 2 years. Patients with severe mental illness were randomised to IPS or local vocational services (treatment as usual). Service use and costs were measured. Two hundred-nineteen participants were randomised, and 86% re-assessed 2 years later. In the multivariate analysis, relatively low rates of competitive employment were found in both the intervention group and the treatment as usual group, although significantly more patients obtained competitive employment in the treatment arm (22% vs. 11%, p=0.041). There were no significant differences in costs. The employment rate among participants receiving IPS was lower than in previously published reports, and the number needed to treat to obtain the benefit of IPS was relatively high. This may reflect difficulties in the implementation of IPS where it is not structurally integrated within mental health teams, as well as economic disincentives which lead to lower levels of motivation for patients and mental health professionals.

Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial

Objective To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. Design Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. Setting 24 rheumatology clinics in England. Participants Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. Interventions Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. Main outcome measure Primary outcome: reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. Secondary outcomes: quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. Results 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of −0.30 with the tumour necrosis factor inhibitor strategy and −0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was −0.14, and the 95% confidence interval (−0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (€4930,

Diagnostic change 10 years after a first episode of psychosis

5585) for months 0-6 and £1930 for months 6-12. Conclusions In patients with active rheumatoid arthritis who meet English criteria for biologics an alternative strategy with combinations of intensive synthetic disease modifying drugs gives non-inferior outcomes to treatment with tumour necrosis factor inhibitors. Costs are reduced substantially. Trial Registration ISRCTN 37438295.

Diagnostic Stability of ICD/DSM First Episode Psychosis Diagnoses: Meta-analysis

Background A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change. Method Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests. Results Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. Conclusions Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes

Background: Validity of current International Classification of Disease/Diagnostic and Statistical Manual of Mental Disorders (ICD/DSM) first episode psychosis diagnoses is essential in clinical practice, research, training and public health. Method: We provide a meta-analytical estimate of prospective diagnostic stability and instability in ICD-10 or DSM-IV first episode diagnoses of functional psychoses. Independent extraction by multiple observers. Random effect meta-analysis conducted with the “metaprop,” “metaninf,” “metafunnel,” “metabias,” and “metareg” packages of STATA13.1. Moderators were tested with meta-regression analyses. Heterogeneity was assessed with the I 2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and Egger’s test. Findings: 42 studies and 45 samples were included, for a total of 14 484 first episode patients and an average follow-up of 4.5 years. Prospective diagnostic stability ranked: schizophrenia 0.90 (95% CI 0.85–0.95), affective spectrum psychoses 0.84 (95% CI 0.79–0.89), schizoaffective disorder 0.72 (95% CI 0.61–0.73), substance-induced psychotic disorder 0.66 (95% CI 0.51–0.81), delusional disorder 0.59 (95% CI 0.47–0.71), acute and transient psychotic disorder/brief psychotic disorder 0.56 (95% CI 0.62–0.60), psychosis not otherwise specified 0.36 (95% CI 0.27–0.45, schizophreniform disorder 0.29 (95% CI 0.22–0.38). Diagnostic stability within schizophrenia spectrum psychoses was 0.93 (95% CI 0.89–0.97); changes to affective spectrum psychoses were 0.05 (95% CI 0.01–0.08). About 0.10 (95% CI 0.05–0.15) of affective spectrum psychoses changed to schizophrenia spectrum psychosis. Across the other psychotic diagnoses there was high diagnostic instability, mostly to schizophrenia. Interpretation: There is meta-analytical evidence for high prospective diagnostic stability in schizophrenia spectrum and affective spectrum psychoses, with no significant ICD/DSM differences. These results may inform the development of new treatment guidelines for early psychosis and impact drug licensing from regulatory agencies.