Improving understanding and utilization of the antibiogram among medical residents.

In this quality improvement project, we sought to increase the understanding and utilization of the antibiogram among physicians in family medicine, internal medicine, and surgery residency programs at a Midwest Academic Healthcare institution. Through simple, inexpensive measures the comfort with, access to, and utilization of the antibiogram can be improved.

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology.

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Impact of secondary care financial incentives on the quality of physical healthcare for people with psychosis: a longitudinal controlled study.

BACKGROUND: Concerns have repeatedly been expressed about the quality of physical healthcare that people with psychosis receive. AIMS: To examine whether the introduction of a financial incentive for secondary care services led to improvements in the quality of physical healthcare for people with psychosis. METHOD: Longitudinal data were collected over an 8-year period on the quality of physical healthcare that people with psychosis received from 56 trusts in England before and after the introduction of the financial incentive. Control data were also collected from six health boards in Wales where a financial incentive was not introduced. We calculated the proportion of patients whose clinical records indicated that they had been screened for seven key aspects of physical health and whether they were offered interventions for problems identified during screening. RESULTS: Data from 17 947 people collected prior to (2011 and 2013) and following (2017) the introduction of the financial incentive in 2014 showed that the proportion of patients who received high-quality physical healthcare in England rose from 12.85% to 31.65% (difference 18.80, 95% CI 17.37-20.21). The proportion of patients who received high-quality physical healthcare in Wales during this period rose from 8.40% to 13.96% (difference 5.56, 95% CI 1.33-10.10). CONCLUSIONS: The results of this study suggest that financial incentives for secondary care mental health services are associated with marked improvements in the quality of care that patients receive. Further research is needed to examine their impact on aspects of care that are not incentivised.

Factors influencing use of community treatment orders and quality of care that people receive: results of a national survey in England and Wales.

Aims and methodWe conducted a secondary analysis of data from the National Audit of Psychosis to identify factors associated with use of community treatment orders (CTOs) and assess the quality of care that people on CTOs receive. RESULTS: Between 1.1 and 20.2% of patients in each trust were being treated on a CTO. Male gender, younger age, greater use of in-patient services, coexisting substance misuse and problems with cognition predicted use of CTOs. Patients on CTOs were more likely to be screened for physical health, have a current care plan, be given contact details for crisis support, and be offered cognitive-behavioural therapy.Clinical implicationsCTOs appear to be used as a framework for delivering higher-quality care to people with more complex needs. High levels of variation in the use of CTOs indicate a need for better evidence about the effects of this approach to patient care.Declaration of interestNone.

Loss of relational continuity of care in schizophrenia: associations with patient satisfaction and quality of care.

BACKGROUND: Users of mental health service are concerned about changes in clinicians providing their care, but little is known about their impact. AIMS: To examine associations between changes in staff, and patient satisfaction and quality of care. METHOD: A national cross-sectional survey of 3379 people aged 18 or over treated in secondary care for schizophrenia or schizoaffective disorder. RESULTS: Nearly 41.9% reported at least one change in their key worker during the previous 12 months and 10.5% reported multiple changes. Those reporting multiple changes were less satisfied with their treatment and less likely to report having a care plan, knowing how to obtain help when in a crisis or to have had recommended physical health assessments. CONCLUSIONS: Frequent changes in staff providing care for people with psychosis are associated with poorer quality of care. Greater efforts need to be made to protect relational continuity of care for such patients. DECLARATION OF INTEREST: M.J.C. was co-chair of the expert advisory group on the NICE quality standard on Service User Experience in Adult Mental Health. S.J.C. has previously been a member of the Health and Social Care Board Northern Ireland Formulary Committee. D.S. received a speaker's fee from Janssen Cilag in 2011. He is a topic expert on NICE guideline for psychosis and schizophrenia in children and young people and a board member of National Collaborating Centre for Mental Health. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment.

Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users' negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance ('pre-diabetes'), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines.These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these.

Exposure to Political Violence in Northern Ireland and Outcome of First Episode Psychosis.

The impact of political violence on individuals presenting with an episode of first episode psychosis has not been examined. Individuals were assessed for exposure to political violence in Northern Ireland (the "Troubles") by asking for a response to 2 questions: one asked about the impact of violence "on your area"; the second about the impact of violence "on you or your family's life." The participants were separated into 2 groups (highandlowimpact) for each question. Symptom profiles and rates of substance misuse were compared across the groups at baseline and at 3-year follow up. Of the 178 individuals included in the study 66 (37.1%) reported ahighimpact of the "Troubles" on their life and 81 (45.5%) ahighimpact of the "Troubles" on their area. There were no significant differences in symptom profile or rates of substance misuse betweenhighandlowgroups at presentation. At 3-year follow-uphighimpact of the "Troubles" on life was associated with higher Positive and Negative Symptom Scale (PANSS) Total (P= .01), PANSS-Positive (P< .05), and PANSS-General (P< .01) scores and lower global assessment of functioning disability (P< .05) scores, after adjusting for confounding factors. Impact of the "Troubles" on area was not associated with differences in symptom outcomes. This finding adds to the evidence that outcomes in psychosis are significantly impacted by environmental factors and suggests that greater attention should be paid to therapeutic strategies designed to address the impact of trauma.

Assessment and treatment of physical health problems among people with schizophrenia: national cross-sectional study.

BACKGROUND: In the UK and other high-income countries, life expectancy in people with schizophrenia is 20% lower than in the general population. AIMS: To examine the quality of assessment and treatment of physical health problems in people with schizophrenia. Method Retrospective audit of records of people with schizophrenia or schizoaffective disorder aged ⩾18. We collected data on nine key aspects of physical health for 5091 patients and combined these with a cross-sectional patient survey. RESULTS: Body mass index was recorded in 2599 (51.1%) patients during the previous 12 months and 1102 (21.6%) had evidence of assessment of all nine key measures. Among those with high blood sugar, there was recorded evidence of 53.5% receiving an appropriate intervention. Among those with dyslipidaemia, this was 19.9%. Despite this, most patients reported that they were satisfied with the physical healthcare they received. CONCLUSIONS: Assessment and treatment of common physical health problems in people with schizophrenia falls well below acceptable standards. Cooperation and communication between primary and secondary care services needs to improve if premature mortality in this group is to be reduced.

Quality of prescribing for schizophrenia: evidence from a national audit in England and Wales.

The National Audit of Schizophrenia (NAS) examined the quality of care received in England and Wales. Part of the audit set out to determine whether six prescribing standards, set by the national clinical guidelines for schizophrenia, were being implemented and to prompt improvements in care. Mental Health Trusts and Health Boards provided data obtained from case-notes for adult patients living in the community with schizophrenia or schizoaffective disorder. An audit of practice tool was developed for data collection. Most of the 5055 patients reviewed were receiving pharmacological treatment according to national guidelines. However, 15.9% of the total sample (95%CI: 14.9-16.9) were prescribed two or more antipsychotics concurrently and 10.1% of patients (95%CI: 9.3-10.9) were prescribed medication in excess of recommended limits. Overall 23.7% (95%CI: 22.5-24.8) of patients were receiving clozapine. However, there were many with treatment resistance who had no clear reason documented as to why they had not had a trial of clozapine (430/1073, 40.1%). In conclusion, whilst most people were prescribed medication in accordance with nationally agreed standards, there was considerable variation between service providers. Antipsychotic polypharmacy, high dose prescribing and clozapine underutilisation in treatment resistance were all key concerns which need to be further addressed.

The obesity risk gene FTO influences body mass in chronic schizophrenia but not initial antipsychotic drug-induced weight gain in first-episode patients.

Genetic factors contribute to the individual variability in weight gain caused by several antipsychotic drugs. The FTO gene is associated with obesity in the general population; we have investigated whether a common risk polymorphism (rs9939609) in this gene is associated with antipsychotic drug-induced weight gain and obesity. Two samples were studied: (1) 93 first-episode patients receiving antipsychotic drugs for the first time and having body weight monitored for up to 12 months; (2) 187 chronic patients with schizophrenia assessed for measures of obesity and metabolic dysfunction. No association of FTO genotype with weight gain was found in initially drug-naive patients. The chronically treated patients had a significant association of genotype with body mass index (BMI), reflected in associations with waist circumference, waist:hip ratio and the frequency of central obesity. These findings indicate that FTO genotype has a major effect on body weight determined by BMI in chronically treated patients with schizophrenia.

A voxel based morphometry study investigating brain structural changes in first episode psychosis.

Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent. SCZ (N=25) and BP (N=24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls. For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites. At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration.

Structural changes in the hippocampus and amygdala at first episode of psychosis.

Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ.

Tryptophan depletion impairs object-recognition memory in the rat: reversal by risperidone.

Tryptophan depletion techniques are effective in reducing central serotonergic function and have been used to investigate its role in mood and cognition. In the present study a tryptophan-free diet was fed to Lister-hooded male rats chronically for 21 days to investigate the effect of lowering central serotonin concentration on cognition using the novel object-recognition paradigm. Chronically tryptophan-depleted rats had impaired object-recognition memory; this was accompanied by a reduction in central serotonin of 40-50% in the hippocampus, frontal cortex and striatum. In a subsequent experiment, the atypical antipsychotic, risperidone (0.2 mg/kg), but not the typical antipsychotic, haloperidol (0.1 mg/kg), administered i.p. 30 min prior to the retention test, significantly attenuated the chronic tryptophan depletion impairment. These data show that chronic lowering of central serotonin is associated with impaired cognitive performance, and that this can be reversed by the atypical antipsychotic, risperidone.

Impact of persistent substance misuse on 1-year outcome in first-episode psychosis.

BACKGROUND: Substance misuse is a common comorbid problem in people presenting with first-episode psychosis and is associated with a poor short-term outcome. AIMS: The aim of this study is to examine differences in baseline characteristics and 1-year outcome between individuals with first-episode psychosis who have never misused substances, those who stop misusing substances after initial presentation and those who persistently misuse substances over the 1-year assessment period. METHOD: Patients were recruited to the Northern Ireland First Episode Psychosis Study (n = 272). Clinical assessments were performed at baseline and at 1 year (n = 194) and data were collected from the case notes. RESULTS: Individuals with persistent substance misuse had more severe depression, more positive symptoms, poorer functional outcome and greater rates of relapse at 1 year than those who stopped and those who had never misused substances. There were no differences in outcome between people who had never misused substances and those who stopped misusing after presentation. CONCLUSIONS: These results support assertive intervention targeted at comorbid substance misuse in individuals with first-episode psychosis.

Patterns of neurocognitive impairment in first-episode bipolar disorder and schizophrenia.

BACKGROUND: Researching psychotic disorders in unison rather than as separate diagnostic groups is widely advocated, but the viability of such an approach requires careful consideration from a neurocognitive perspective. AIMS: To describe cognition in people with bipolar disorder and schizophrenia and to examine how known causes of variability in individual's performance contribute to any observed diagnostic differences. METHOD: Neurocognitive functioning in people with bipolar disorder (n = 32), schizophrenia (n = 46) and healthy controls (n = 67) was compared using analysis of covariance on data from the Northern Ireland First Episode Psychosis Study. RESULTS: The bipolar disorder and schizophrenia groups were most impaired on tests of memory, executive functioning and language. The bipolar group performed significantly better on tests of response inhibition, verbal fluency and callosal functioning. Between-group differences could be explained by the greater proclivity of individuals with schizophrenia to experience global cognitive impairment and negative symptoms. CONCLUSIONS: Particular impairments are common to people with psychosis and may prove useful as endophenotypic markers. Considering the degree of individuals' global cognitive impairment is critical when attempting to understand patterns of selective impairment both within and between these diagnostic groups.

Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia.

BACKGROUND: Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors. AIMS: To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia. METHOD: Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT(2C) receptor -759C/T and leptin -2548A/G). RESULTS: Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine. CONCLUSIONS: The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

Acute tryptophan depletion does not alter central or plasma brain-derived neurotrophic factor in the rat.

Dietary induced acute tryptophan depletion (ATD) is used to reduce central serotonergic function and to investigate the role of serotonin (5-HT) in psychiatric illness. In healthy volunteers ATD produces working memory deficits and decreases mood in some studies. Brain-derived neurotrophic factor (BDNF) plays a role in both cognition and in the regulation of mood; however, the possible contribution of central BDNF changes to the effects of ATD has not been examined. Therefore, using a rat model we have examined the effect of amino acid mixture-induced ATD on plasma and central BDNF protein levels. ATD significantly reduced free-plasma TRP by 79% and central hippocampal 5-HT by 35% when compared to controls. However, plasma or central BDNF protein levels in the hippocampus and midbrain were not significantly altered by ATD. These results suggest that changes in central BDNF do not contribute to the cognitive or mood effects of ATD.

Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT 2A receptor binding in the rat.

RATIONALE: Tryptophan depletion is used to reduce central serotonergic function and to investigate its role in psychiatric illness. Despite widespread clinical use, its effects on serotonin (5-HT) receptors have not been well characterized. OBJECTIVE: The aim of this study was to examine the effect of acute (ATD) and chronic tryptophan depletion (CTD) on free-plasma tryptophan (TRP), central TRP and 5-HT and brain 5-HT(1A) and 5-HT(2A) receptor binding in the rat. METHODS: TRP and 5-HT were measured by high-performance liquid chromatography and receptor levels determined by homogenate radioligand binding and in-vitro receptor autoradiography. RESULTS: Free-plasma TRP, central TRP and central 5-HT levels were significantly and similarly reduced by ATD and 1- and 3-week CTD compared to controls. ATD significantly reduced 5-HT(1A) binding in the dorsal raphe (14%) but did not significantly alter postsynaptic 5-HT(1A) binding (frontal cortex, remaining cortex and hippocampus) or 5-HT(2A) binding (cortex and striatum). One-week CTD did not significantly alter cortical 5-HT(2A) binding or postsynaptic 5-HT(1A) binding. Furthermore, 3-week CTD did not significantly alter 5-HT(1A) binding but significantly increased cortical 5-HT(2A) binding without affecting striatal or hippocampal levels. In the CTD 1 and 3-week groups, rat body weight was significantly decreased as compared to controls. However, weight loss was not a confounding factor for decreased cortical 5-HT(2A)-receptor binding. CONCLUSION: ATD-induced reduction in somatodendritic 5-HT(1A) autoreceptor binding may represent an intrinsic 'homeostatic response' reducing serotonergic feedback in dorsal raphe projection areas. In contrast, the increase in 5-HT(2A) receptor after CTD may be a compensatory response to a long-term reduction in 5-HT.

Anterior cingulate and subgenual prefrontal blood flow changes following tryptophan depletion in healthy males.

In healthy humans, there is an apparent dissociation between cognitive and affective consequences of reduced brain serotonin (5-HT), as rapid tryptophan depletion (RTD) causes alterations in a consistent constellation of cognitive processes in the general absence of mood deterioration. This study aimed to investigate possible neural mechanisms underlying this relative dissociation by measuring the effects of reduced 5-HT on regional cerebral blood flow (rCBF). A total of 16 healthy, euthymic male subjects (mean age 39+/-9 years) without a personal or family history of affective disorder had mood ratings and single photon emission computed tomography scans with the rCBF tracer 99mTc-HMPAO under reduced 5-HT (RTD) and control conditions. Across individuals, modest positive and negative changes in subjective happiness associated with RTD were significantly correlated with change of rCBF in a cluster comprising subgenual (affective) anterior cingulate cortex (ACC) and associated regions (Brodmann's area (BA) 25, posterior BA11 and 47, caudate nucleus and ventral striatum; SPM99 p<0.05, corrected). The covariation was such that increasing sadness was associated with increased rCBF and vice versa. Independent of mood change, RTD was associated with reduced rCBF in the dorsal (cognitive) ACC (BA32; SPM99 p<0.05, corrected). The subgenual prefrontal cortex and dorsal ACC are important components of the ventral and dorsal neural systems that regulate and integrate affective and cognitive functions. The results therefore suggest that the dissociation between affective and cognitive consequences of RTD may possibly be attributable to differential effects of reduced 5-HT on these neural systems.

Rapid tryptophan depletion improves decision-making cognition in healthy humans without affecting reversal learning or set shifting.

Rapid tryptophan (Trp) depletion (RTD) has been reported to cause deterioration in the quality of decision making and impaired reversal learning, while leaving attentional set shifting relatively unimpaired. These findings have been attributed to a more powerful neuromodulatory effect of reduced 5-HT on ventral prefrontal cortex (PFC) than on dorsolateral PFC. In view of the limited number of reports, the aim of this study was to independently replicate these findings using the same test paradigms. Healthy human subjects without a personal or family history of affective disorder were assessed using a computerized decision making/gambling task and the CANTAB ID/ED attentional set-shifting task under Trp-depleted (n=17; nine males and eight females) or control (n=15; seven males and eight females) conditions, in a double-blind, randomized, parallel-group design. There was no significant effect of RTD on set shifting, reversal learning, risk taking, impulsivity, or subjective mood. However, RTD significantly altered decision making such that depleted subjects chose the more likely of two possible outcomes significantly more often than controls. This is in direct contrast to the previous report that subjects chose the more likely outcome significantly less often following RTD. In the terminology of that report, our result may be interpreted as improvement in the quality of decision making following RTD. This contrast between studies highlights the variability in the cognitive effects of RTD between apparently similar groups of healthy subjects, and suggests the need for future RTD studies to control for a range of personality, family history, and genetic factors that may be associated with 5-HT function.