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Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
A recent editorial claimed that the 2014 National Institute for Health and Care Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent 2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased towards psychosocial treatments and against drug treatments. In this paper we underline that the NICE and SIGN guidelines recommend similar interventions, but that the NICE guideline has more rigorous methodology. Our analysis suggests that the authors of the editorial appear to have succumbed to bias themselves.
Social disability is a hallmark of severe mental illness yet individual
differences and factors predicting outcome are largely unknown.
To explore trajectories and predictors of social recovery following a
first episode of psychosis (FEP).
A sample of 764 individuals with FEP were assessed on entry into early
intervention in psychosis (EIP) services and followed up over 12 months.
Social recovery profiles were examined using latent class growth
Three types of social recovery profile were identified: Low Stable (66%),
Moderate-Increasing (27%), and High-Decreasing (7%). Poor social recovery
was predicted by male gender, ethnic minority status, younger age at
onset of psychosis, increased negative symptoms, and poor premorbid
Social disability is prevalent in FEP, although distinct recovery
profiles are evident. Where social disability is present on entry into
EIP services it can remain stable, highlighting a need for targeted
Early intervention services (EIS) comprise low-stigma, youth-friendly mental health teams for young people undergoing first-episode psychosis (FEP). Engaging with the family of the young person is central to EIS policy and practice.
By analysing carers' accounts of their daily lives and affective challenges during a relative's FEP against the background of wider research into EIS, this paper explores relationships between carers' experiences and EIS.
Semi-structured longitudinal interviews with 80 carers of young people with FEP treated through English EIS.
Our data suggest that EIS successfully aid carers to support their relatives, particularly through the provision of knowledge about psychosis and medications. However, paradoxical ramifications of these user-focused engagements also emerge; they risk leaving carers' emotions unacknowledged and compounding an existing lack of help-seeking.
By focusing on EIS's engagements with carers, this paper draws attention to an urgent broader question: as a continuing emphasis on care outside the clinic space places family members at the heart of the care of those with severe mental illness, we ask: who can, and should, support carers, and in what ways?
Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed.
To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway.
Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed.
A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP.
Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.
The Gemini Planet Imager (GPI) is a high contrast coronagraph designed to directly image exoplanets and circumstellar disks. GPI includes a polarimetry mode designed to characterize dust grains and enhance the contrast of scattered, polarized light by a factor of 100. Reflections and birefringence of optics within the optical train induce a polarization signature that needs to be measured a priori and calibrated out during data reduction. Here we report on the results of an extensive laboratory characterization campaign of the polarimetry mode. The linear instrumental polarization has been measured in 4 GPI passbands and found to be between 3.5 ± 0.3 % at 1.0 micron and 1.1 ± 0.3 % at 2.0 microns. Modulation efficiency has been measured to be 94% at 1.0 micron increasing to 97% at 2.0 microns. Stability has been shown to better than 0.6% over timescales of ~ 3 months and over cool down cycles. The tests show that GPI passes all polarimetry design requirements and should be able to measure circumstellar disk linear polarization to 1% accuracy.
Received internationalization theory argues that firms occupy domestic space before going abroad; in other words, large, oligopolistic firms are most likely to internationalize. The experience of China, whose economy is fragmented and whose firms are small by global standards, suggests otherwise. We construct a model of small firm internationalization driven by the relative transaction costs of crossing domestic (in the case of China, provincial) and international borders. When the costs of crossing domestic borders exceed the costs of crossing international borders, firms will internationalize at a relatively early stage of development. In the case of China, local protectionism and inefficient domestic logistics increase the costs of doing business domestically; moreover, protection of property rights in the West and the advantages afforded Chinese owned firms reconstituted as foreign entities operating in China decrease the costs of ‘going out’. We coin the term ‘institutional arbitrage’ to capture Chinese firms' pursuit of efficient institutions outside of China. We argue that strategic exit from the home country rather than strategic entry into foreign markets may explain the internationalization of many Chinese firms.
The aims of the Editorial are to summarise what we know for certain from clinical trials of Intensive Case Management, and to highlight lessons for clinicians and researchers. I will upon two systematic reviews of trials of Intensive Case Management versus standard care or low intensity case management. Both incorporated a meta-regression which examined the effect of fidelity to the Assertive Community Treatment model on outcome. The effectiveness of Intensive Case Management was limited to improving patient satisfaction and reducing attrition. Intensive Case Management teams organised according to the Assertive Community Treatment model offered the additional benefit of reducing days in hospital, but only when the team's clients had been high users of hospital care over the previous 12 months. Four important lessons can be drawn: a) Changes to the process of care tend to affect process variables, not outcome variables. b) Complex interventions must be defined meticulously in clear terminology. c) Researchers must demonstrate that complex interventions have been properly implemented in clinical trials. d) It is important to remember that in a clinical trial a successful outcome is determined as much by the control group as by the intervention.
A major reason for interest in early intervention for psychotic disorders is the hypothesised relationship between longer duration of untreated psychosis (DUP) and poorer outcome of treatment.
To critically examine the evidence concerning DUP being related to treatment outcome and possible mediators of any such relationship.
A systematic review of studies in which DUP is assessed and its relationship to treatment outcome is examined. In addition, studies relevant to possible neurotoxic effects of DUP were reviewed.
The research is entirely of a correlational nature and, therefore, firm conclusions regarding causation are not possible. There is, however, substantial evidence of DUP being an independent predictor of treatment outcome, particularly remission of positive symptoms, over the first year or so of treatment. Findings regarding the possible neurotoxic effects of DUP are inconsistent.
There continues to be evidence consistent with DUP influencing aspects of treatment outcome. Non-correlational studies, such as quasi-experimental designs, could provide stronger evidence regarding causality.
A recent review suggested an association between using unpublished scales in clinical trials and finding significant results.
To determine whether such an association existed in schizophrenia trials.
Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded.
Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% C11.12–1.68)). This effect increased when a ‘gold-standard’ definition of treatment superiority was applied (RR 1.94 (95% C11.35–2.79)). In non-pharmacological trials, one-third of ‘gold-standard’ claims of treatment superiority would not have been made if published scales had been used.
Unpublished scales are a source of bias in schizophrenia trials.
Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care.
Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial.
At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86–1.38) for total costs; 1.12 (0.76–1.65) for state benefits, and 1.21 (0.61–2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant.
Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy.
This chapter is in two sections. The first section will be a survey of the types of evaluative studies that have been conducted on services for homeless people with mental disorders. The survey will pay particular attention to the problems that have arisen in carrying out these studies. This section will be illustrated throughout by examples of evaluative studies from the UK literature; where UK studies are lacking, examples will be taken from the world literature.
The second section will consider how far evaluative studies have provided evidence for the effectiveness of hostels for the homeless. As indicated in Chapter 9 the role of hostels in this area is increasingly controversial.
A Survey of Evaluative Studies
Evaluative studies of services for homeless people with mental disorders can be classified according to design. Such a classification produces the following broad groupings:
Evaluations based on the impressions of a trained observer.
Before and after evaluations.
Single case and ‘action research’ evaluations.
Randomized controlled trials.
Examples of evaluations from each of these groupings will be discussed below. The discussion will pay particular attention to the reasons for adopting particular designs and the problems that arise in implementing these designs with homeless subjects.
Retrospective evaluations are based on the analysis of routine data collected during clinical work.
Uses of retrospective evaluations
Retrospective evaluations may usefully describe the structure of a new service and the activities of that service.
Reviews of homelessness and mental disorder in the UK inevitably draw comparisons with the situation in the USA (for example Scott, 1993). It is often assumed that the findings of any US study of homeless people (from the level of frostbite in New York to the rates of drug abuse in homeless women) are unquestionably generalizeable to UK populations. In fact close comparisons between the USA and UK are sometimes seriously misleading. In a Western democracy, the level of homelessness is essentially a product of social policy, and so too is the level of mental disorder amongst the homeless. In social policy terms, (for example, in the provision of subsidized housing, free health care, and state benefits) the UK now stands somewhere between American and European norms. Thus, the UK resembles the USA in that it has increasingly adopted a free market housing policy. On the other hand, the UK government remains committed (in public) to the European ethos of a national health service, and a reasonable level of state assistance to the unemployed and disabled.
Mental disorder in homeless women is a good example of an area where USA—UK comparisons may mislead, when differences in social policy are not taken into account. In the UK, local authorities are obliged to provide emergency accommodation to homeless families (usually a lone woman with children), and to rehouse such families as a priority. Whilst these families may face long periods in temporary accommodation (bedsits), they are eventually rehoused, and do not have to make use of emergency shelters or hostels. In the USA there is usually no obligation to rehouse homeless families.