A service evaluation study of the impact of ageless policy in a London inner-city early intervention in psychosis service.

BACKGROUND: Schizophreniform disorders tend to have an early onset. Early intervention in psychosis (EIP) services aim to provide early treatment, reduce long-term morbidity and improve social functioning. In 2016, changes to mental health policy in England mandated that the primarily youth-focused model should be extended to an ageless one, to prevent ageism; however, this was without strong research evidence. AIMS AND METHOD: An inner-city London EIP service compared sociodemographic and clinical factors between the under-35 years and over-35 years caseload cohorts utilising the EIP package following the implementation of the ageless policy. RESULTS: Both groups received similar care, despite the younger group having significantly more clinical morbidity and needs. CLINICAL IMPLICATIONS: Our results may indicate that service provisions are being driven by policy rather than clinical needs, potentially diverting resources from younger patients. These findings have important implications for future provision of EIP services and would benefit from further exploration.

Establishing a business case for setting up early detection services for preventing psychosis.

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new 'access and waiting times' standard for early intervention in psychosis to extend the prevention of psychosis across England. Unfortunately, early intervention and early detection services are still not uniformly distributed in the UK, leaving gaps in service provision. The aim of this paper is to provide a business case model that can guide clinicians and services looking to set up or expand early detection services in their area. The paper also focuses on some existing models of care within the Pan-London Network for Psychosis Prevention teams.

Proteomic biomarkers of Kleine-Levin syndrome.

STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. METHODS: SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. RESULTS: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. CONCLUSIONS: Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.

Research by Psychiatric Trainees and Early Career Psychiatrists-Results of a Survey From 34 Countries in Europe.

Clinical psychiatric practice should be intricately linked with research work. Although psychiatric trainees and early career psychiatrists (ECPs) are in the frontline of clinical services, little is known about how much access they have to research opportunities. A semi-structured questionnaire of 35 questions-exploring research goals achieved, facilitators and barriers as well as personal context-was sent to psychiatric trainees and ECPs across Europe. The survey was disseminated through the local committees of the main professional psychiatric societies in Europe. A total of 258 individuals working in 34 European countries participated. The majority (69.8%) were psychiatric trainees within training in adult psychiatry. Most participants (69.0%) were highly interested in research, but faced major obstacles toward their research activities, such as lack of time and funding. They were highly satisfied with mentoring and publishing papers. Only half of the participants, however, had already published a scientific article, and only a few have been able to contribute to randomized clinical trials (20.9%). A large proportion of participants (87.2%) reported to conduct research after or during a mixture of working hours and after working hours. Only one tenth ever received a grant for their work. These findings highlight that the key barriers for the performance of research are lack of time and funding. Psychiatric trainees and ECPs are motivated to perform research but need support and regular opportunities.

Establishing a clinical service to prevent psychosis: What, how and when? Systematic review.

The first rate-limiting step to successfully translate prevention of psychosis in to clinical practice is to establish specialised Clinical High Risk for Psychosis (CHR-P) services. This study systematises the knowledge regarding CHR-P services and provides guidelines for translational implementation. We conducted a PRISMA/MOOSE-compliant (PROSPERO-CRD42020163640) systematic review of Web of Science to identify studies until 4/05/2020 reporting on CHR-P service configuration, outreach strategy and referrals, service user characteristics, interventions, and outcomes. Fifty-six studies (1998-2020) were included, encompassing 51 distinct CHR-P services across 15 countries and a catchment area of 17,252,666 people. Most services (80.4%) consisted of integrated multidisciplinary teams taking care of CHR-P and other patients. Outreach encompassed active (up to 97.6%) or passive (up to 63.4%) approaches: referrals came mostly (90%) from healthcare agencies. CHR-P individuals were more frequently males (57.2%). Most (70.6%) services accepted individuals aged 12-35 years, typically assessed with the CAARMS/SIPS (83.7%). Baseline comorbid mental conditions were reported in two-third (69.5%) of cases, and unemployment in one third (36.6%). Most services provided up to 2-years (72.4%), of clinical monitoring (100%), psychoeducation (81.1%), psychosocial support (73%), family interventions (73%), individual (67.6%) and group (18.9%) psychotherapy, physical health interventions (37.8%), antipsychotics (87.1%), antidepressants (74.2%), anxiolytics (51.6%), and mood stabilisers (38.7%). Outcomes were more frequently ascertained clinically (93.0%) and included: persistence of symptoms/comorbidities (67.4%), transition to psychosis (53.5%), and functional status (48.8%). We provide ten practical recommendations for implementation of CHR-P services. Health service knowledge summarised by the current study will facilitate translational efforts for implementation of CHR-P services worldwide.

Pan-London Network for Psychosis-Prevention (PNP).

Background: The empirical success of the Clinical High Risk for Psychosis (CHR-P) paradigm is determined by the concurrent integration of efficient detection of cases at-risk, accurate prognosis, and effective preventive treatment within specialized clinical services. The characteristics of the CHR-P services are relatively under-investigated. Method: A Pan-London Network for psychosis prevention (PNP) was created across urban CHR-P services. These services were surveyed to collect the following: description of the service and catchment area, outreach, service users, interventions, and outcomes. The results were analyzed with descriptive statistics and Kaplan Meier failure function. Results: The PNP included five CHR-P services across two NHS Trusts: Outreach and Support In South-London (OASIS) in Lambeth and Southwark, OASIS in Croydon and Lewisham, Tower Hamlets Early Detection Service (THEDS), City & Hackney At-Risk Mental State Service (HEADS UP) and Newham Early Intervention Service (NEIS). The PNP serves a total population of 2,318,515 Londoners (830,889; age, 16-35 years), with a yearly recruitment capacity of 220 CHR-P individuals (age, 22.55 years). Standalone teams (OASIS and THEDS) are more established and successful than teams that share their resources with other mental health services (HEADS UP, NEIS). Characteristics of the catchment areas, outreach and service users, differ across PNP services; all of them offer psychotherapy to prevent psychosis. The PNP is supporting several CHR-P translational research projects. Conclusions: The PNP is the largest CHR-P clinical network in the UK; it represents a reference benchmark for implementing detection, prognosis, and care in the real-world clinical routine, as well as for translating research innovations into practice.

The PsyLOG mobile application: development of a tool for the assessment and monitoring of side effects of psychotropic medication.

Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

INTRODUCTION: A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. METHODS: A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. RESULTS: HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, p<0.001 (55.4% higher HVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001), higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001), and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025). One hundred and two (18.5%) of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. CONCLUSIONS: This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

Equal access for all? Access to medical information for European psychiatric trainees.

Access to medical information is important as lifelong scientific learning is in close relation with a better career satisfaction in psychiatry. This survey aimed to investigate how medical information sources are being used among members of the European Federation of Psychiatric Trainees. Eighty-three psychiatric trainees completed our questionnaire. A significant variation was found, and information availability levels were associated with training duration and average income. The most available sources were books and websites, but the most preferred ones were scientific journals. Our findings suggest that further steps should be taken to provide an equal access to medical information across Europe.

Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia.

Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients' evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers.

Training in sleep medicine among European early career psychiatrists: a project from the European Psychiatric Association--Early Career Psychiatrists Committee.

INTRODUCTION: Sleep disorders have a proven association with psychiatric illness. Therefore, psychiatrists require appropriate training in diagnosing and treating sleep disorders. To date, there is no data available in Europe on training in sleep medicine for early career psychiatrists (ECP). AIMS: To identify the availability of training in sleep medicine for psychiatric trainees across Europe and to establish how confident doctors feel in treating these conditions. METHODS: European-wide survey carried out by the European Psychiatric Association (EPA)-Early Career Psychiatrists Committees. Representatives of ECPs from each participating European country filled in a questionnaire about availability of training in sleep medicine in their country. ECPs were also invited to fill out a questionnaire at the EPA congress in Nice in 2013. RESULTS: 55 participants from 27 European countries responded. Only 24% had sleep medicine training mandatorily included in their national training curriculum. A majority (60%) felt that the quality of the training they received was either average or below average. 88% felt either very or fairly confident in treating insomnia. However, when asked to select the correct management options for insomnia from a provided list of six, only 19% and 33% of respondents chose the two correct options. CONCLUSIONS: There is a clear gap between the level of confidence and the clinical judgements being made to treat insomnia among European ECPs. There is a definite need to improve the availability and structure of sleep medicine training for psychiatric trainees in Europe.

Interventions for posttraumatic stress disorder in psychiatric practice across Europe: a trainees' perspective.

BACKGROUND: With an annual prevalence of 0.9-2.6%, posttraumatic stress disorder (PTSD) is very common in clinical practice across Europe. Despite the fact that evidence-based interventions have been developed, there is no evidence on their implementation in clinical practice and in national psychiatric training programmes. OBJECTIVE AND METHOD: The Early Career Psychiatrists Committee of the European Psychiatric Association conducted a survey in 23 European countries to explore implementation of evidence-based interventions for PTSD and training options. RESULTS: The findings indicate that pharmacotherapy was available in the majority of the participating countries (n=19, 82.8%). However, psychological interventions were much less widespread. For example, psychoeducation was widely available in 52% of the countries (n=12), cognitive-behavioural therapy in 26.2% (n=6), and specific trauma-focused techniques were rarely available. Training on PTSD was part of the official training in 13 countries (56.5%), predominantly in the form of theoretical seminars. CONCLUSIONS: Overall, this survey indicates that the treatment for PTSD is largely focused on pharmacotherapy, with psychological evidence-based interventions poorly available, especially outside specialized centres. Poor implementation is linked to the lack of official training in evidence-based interventions for psychiatric trainees across Europe.

Exploring medical diagnostic performance using interactive, multi-parameter sourced receiver operating characteristic scatter plots.

Determining diagnostic criteria for specific disorders is often a tedious task that involves determining optimal diagnostic thresholds for symptoms and biomarkers using receiver-operating characteristic (ROC) statistics. To help this endeavor, we developed softROC, a user-friendly graphic-based tool that lets users visually explore possible ROC tradeoffs. The software requires MATLAB installation and an Excel file containing threshold symptoms/biological measures, with corresponding gold standard diagnoses for a set of patients. The software scans the input file for diagnostic and symptom/biomarkers columns, and populates the graphical-user-interface (GUI). Users select symptoms/biomarkers of interest using Boolean algebra as potential inputs to create diagnostic criteria outputs. The software evaluates subtests across the user-established range of cut-points and compares them to a gold standard in order to generate ROC and quality ROC scatter plots. These plots can be examined interactively to find optimal cut-points of interest for a given application (e.g. sensitivity versus specificity needs). Split-set validation can also be used to set up criteria and validate these in independent samples. Bootstrapping is used to produce confidence intervals. Additional statistics and measures are provided, such as the area under the ROC curve (AUC). As a testing set, softROC is used to investigate nocturnal polysomnogram measures as diagnostic features for narcolepsy. All measures can be outputted to a text file for offline analysis. The softROC toolbox, with clinical training data and tutorial instruction manual, is provided as supplementary material and can be obtained online at http://www.stanford.edu/~hyatt4/software/softroc or from the open source repository at http://www.github.com/informaton/softroc.

Encouraging French medical students to choose a career in psychiatry: how and why?

There is an increasing demand for psychiatrists in France. This paper reviews the reasons for French medical students choosing psychiatry and the rationale and mechanisms for encouraging them towards this medical speciality. The main factors associated with choosing psychiatry as a career are the quantity and quality of undergraduate training and placements in psychiatry, better attitudes towards psychiatry and more emphasis on a positive life/work balance. The quality of postgraduate training can also influence students' decisions. Medical students should be encouraged to choose psychiatry first to counterbalance the existing stigma towards mental illness within the society, but also towards psychiatry within the medical profession, and second because of the current decline in French medical demography. Ways to improve recruitment are a selection process that favours a large number of psychiatric trainees, and an increase in the quality and quantity of training. Providing medical students with relevant information about training in psychiatry, notably through a national trainees' association, will not only improve the quality of care by increasing recruitment in psychiatry, but also ensure that all future doctors are familiar with and develop positive attitudes towards mental health issues.

Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.

IMPORTANCE: Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE: To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS: Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES: Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level. RESULTS: Short REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%). CONCLUSIONS AND RELEVANCE: Among patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.

Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy.

STUDY OBJECTIVES: To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1. SETTING: University-based sleep clinics and laboratories. PATIENTS: Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1. DESIGN AND INTERVENTIONS: Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis. MEASUREMENTS AND RESULTS: The optimal cutoff of CSF hypocretin-1 for narcolepsy without cataplexy diagnosis was 200 pg/ml rather than 110 pg/ml (sensitivity 33%, specificity 99%). Forty-one patients (24%), all HLA DQB1*06:02 positive, had low concentrations (≤ 110 pg/ml) of CSF hypocretin-1. Patients with low concentrations of hypocretin-1 only differed subjectively from other groups by a higher Epworth Sleepiness Scale score and more frequent sleep paralysis. Compared with patients with normal hypocretin-1 concentration (n = 117, 68%), those with low hypocretin-1 concentration had higher HLA DQB1*06:02 frequencies, were more frequently non-Caucasians (notably African Americans), with lower age of onset, and longer duration of illness. They also had more frequently short rapid-eye movement (REM) sleep latency (≤ 15 min) during polysomnography (64% versus 23%), and shorter sleep latencies (2.7 ± 0.3 versus 4.4 ± 0.2 min) and more sleep-onset REM periods (3.6 ± 0.1 versus 2.9 ± 0.1 min) during the Multiple Sleep Latency Test (MSLT). Patients with intermediate concentrations of CSF hypocretin-1 (n = 13, 8%) had intermediate HLA DQB1*06:02 and polysomnography results, suggesting heterogeneity. Of the 127 patients we were able to recontact, survival analysis showed that almost half (48%) with low concentration of CSF hypocretin-1 had developed typical cataplexy at 26 yr after onset, whereas only 2% had done so when CSF hypocretin-1 concentration was normal. Almost all patients (87%) still complained of daytime sleepiness independent of hypocretin status. CONCLUSION: Objective (HLA typing, MSLT, and sleep studies) more than subjective (sleepiness and sleep paralysis) features predicted low concentration of CSF hypocretin-1 in patients with narcolepsy without cataplexy.

Factors influencing French medical students towards a career in psychiatry.

BACKGROUND: There is a need to increase the recruitment to psychiatry in France. Our aim in this study was to compare factors influencing career choice between French medical students considering and not considering psychiatry as a specialty. SUBJECTS AND METHODS: Quantitative cross-sectional online survey on 145 French students in their last year of medical school. RESULTS: 22.7% of our sample considered choosing a career in psychiatry. A preference for a career in psychiatry was associated with more frequent history of personal/familial mental illness, higher ratings of psychiatric teaching, more weeks of compulsory psychiatry teaching and placement, during which students had more often met patients in recovery and been asked their opinion on patients. Students considering psychiatry as a career also emphasized more the need for a good work-life balance, and presented better attitudes toward psychiatry. CONCLUSIONS: Improving opportunities of interactions between students and psychiatrists or psychiatric patients might help to improve recruitment in psychiatry.