Identification of radiomic biomarkers in a set of four skeletal muscle groups on Dixon MRI of the NAKO MR study.

In this work, we propose a processing pipeline for the extraction and identification of meaningful radiomics biomarkers in skeletal muscle tissue as displayed using Dixon-weighted MRI. Diverse and robust radiomics features can be identified that may be of aid in the accurate quantification e.g. varying degrees of sarcopenia in respective muscles of large cohorts. As such, the approach comprises the texture feature extraction from raw data based on well established approaches, such as a nnU-Net neural network and the Pyradiomics toolbox, a subsequent selection according to adequate conditions for the muscle tissue of the general population, and an importance-based ranking to further narrow the amount of meaningful features with respect to auxiliary targets. The performance was investigated with respect to the included auxiliary targets, namely age, body mass index (BMI), and fat fraction (FF). Four skeletal muscles with different fiber architecture were included: the mm. glutaei, m. psoas, as well as the extensors and adductors of the thigh. The selection allowed for a reduction from 1015 available texture features to 65 for age, 53 for BMI, and 36 for FF from the available fat/water contrast images considering all muscles jointly. Further, the dependence of the importance rankings calculated for the auxiliary targets on validation sets (in a cross-validation scheme) was investigated by boxplots. In addition, significant differences between subgroups of respective auxiliary targets as well as between both sexes were shown to be present within the ten lowest ranked features by means of Kruskal-Wallis H-tests and Mann-Whitney U-tests. The prediction performance for the selected features and the ranking scheme were verified on validation sets by a random forest based multi-class classification, with strong area under the curve (AUC) values of the receiver operator characteristic (ROC) of 73.03 ± 0.70 % and 73.63 ± 0.70 % for the water and fat images in age, 80.68 ± 0.30 % and 88.03 ± 0.89 % in BMI, as well as 98.36 ± 0.03 % and 98.52 ± 0.09 % in FF.

Dopamine partial agonists: a discrete class of antipsychotics.

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics.Key pointsD2 partial agonists share many pharmacological and clinical propertiesD2 partial agonists differ in several important respects from D2 antagonistsD2 partial agonists should be considered a discrete class of antipsychotics.

Barriers to the management of sexual dysfunction among people with psychosis: analysis of qualitative data from the REMEDY trial.

BACKGROUND: More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial. METHODS: We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis. RESULTS: Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients' mental stability, mutual discomfort and embarrassment about discussing a "taboo" subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these "hidden" side effects. CONCLUSION: The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891.

A systematic review and meta-analysis of the mental health symptoms during the Covid-19 pandemic in Southeast Asia.

AIMS: The Covid-19 pandemic has had a substantial impact on the mental health of the general public and high-risk groups worldwide. Due to its proximity and close links to China, Southeast Asia was one of the first regions to be affected by the outbreak. The aim of this systematic review was to evaluate the prevalence of anxiety, depression and insomnia in the general adult population and healthcare workers (HCWs) in Southeast Asia during the course of the first year of the pandemic. METHODS: Several literature databases were systemically searched for articles published up to February 2021 and two reviewers independently evaluated all relevant studies using pre-determined criteria. The prevalence rates of mental health symptoms were calculated using a random-effect meta-analysis model. RESULTS: In total, 32 samples from 25 studies with 20 352 participants were included. Anxiety was assessed in all 25 studies and depression in 15 studies with pooled prevalence rates of 22% and 16%, respectively. Only two studies assessed insomnia, which was estimated at 19%. The prevalence of anxiety and depression was similar among frontline HCWs (18%), general HCWs (17%), and students (20%) while being noticeably higher in the general population (27%). CONCLUSIONS: This is the first systematic review to investigate the mental health impact of the Covid-19 pandemic in Southeast Asia. A considerable proportion of the general population and HCWs reported mild to moderate symptoms of anxiety and depression; the pooled prevalence rater, however, remain significantly lower than those reported in other areas such as China and Europe.

The Patient, Investigator, Nurse, Carer Questionnaire (PINC-Q): a cross-sectional, retrospective, non-interventional study exploring the impact of less frequent medication administration with paliperidone palmitate 3-monthly as maintenance treatment for schizophrenia.

BACKGROUND: To understand the implications of switching from paliperidone palmitate 1-monthly (PP1M) to paliperidone palmitate 3-monthly (PP3M) treatment of schizophrenia from the perspective of four key stakeholders: patients, physicians, nurses and carers. METHODS: This was a cross-sectional, retrospective, non-interventional study comprising a one-time questionnaire (PINC-Q) for adult patients (aged ≥18 years) with schizophrenia (International Classification of Diseases; ICD-10) and their physician, nurse and carer. Questionnaires were developed in association with patient and carer advocacy groups (GAMIAN and EUFAMI) and following an advisory board formed of psychiatrists and nurses. The degree of alignment between stakeholders was also examined. RESULTS: Responses were received from a total of 224 evaluable patients. For most patients (88.4%), responses were received from at least two other stakeholders. Patients were moderately ill with mild-to-moderate lack of insight and had received PP1M for a mean (standard deviation [SD]) of 23.9 (21.28) months before switching to PP3M (duration mean [SD] 12.8 [3.72] months). The most frequently reported reasons to switch from PP1M to PP3M were 'to live life as normally as possible' and 'patient convenience'. Over 79% of responses within each stakeholder group stated that PP3M helped the patients, with increased patient activity and social involvement, improved frequency and quality of physician-patient and nurse-patient communication and decreased perceived stigma. CONCLUSIONS: The results of this study add to the increasing body of evidence supporting the benefits of PP3M in a population of patients with schizophrenia representative of real-world clinical practice.

Reflections, impact and recommendations of a co-produced qualitative study with young people who have experience of mental health difficulties.

BACKGROUND: There is limited evidence of genuine equal partnership where power is shared with young people with mental health difficulties throughout all research stages, particularly in data collection and analysis. OBJECTIVE: To describe how our qualitative study, exploring young peoples' perceptions on the feasibility of using technology to detect mental health deterioration, was co-produced using principles of co-production, whilst reflecting on impact, challenges and recommendations. METHODS: Young people with experience of mental health difficulties were appointed and then worked with researchers throughout all research stages. The study was evaluated against the five principles of co-production. Reflections from researchers and young people were collected throughout. RESULTS: Seven young people formed an initial Young People's Advisory Group (YPAG); three became co-researchers. Reflection was key throughout the process. Sharing power became easier and more evident as trust, confidence and mutual respect grew over time, particularly after a safe space was established. The safe space was crucial for open discussions, and our WhatsApp group enabled continual communication, support and shared decision-making. The resulting co-produced topic guide, coding framework, thematic map, papers and presentations demonstrated significant impact. CONCLUSIONS: To our knowledge, this is the first qualitative mental health study to be co-produced using the principles of co-production. Our rigorous assessment can be utilized as an informative document to help others to produce meaningful co-produced future research. Although co-production takes time, it makes significant impact to the research, researchers and co-researchers. Flexible funding for spontaneous suggestions from co-researchers and more time for interview training is recommended.

Shared and Supported Decision Making in Medication in a Mental Health Setting: How Far Have We Come?

Personalised care involves shared decision making (SDM) across all levels including choice in medication. However, there are a number of barriers which prevent its effective implementation in routine mental health settings. Therefore, we undertook a study to benchmark current practice across clinical services of a large urban mental health provider. The study formed part of the trust-wide 'Supported Decision Making in Medication' Co-Production Project and aims to inform future recommendations in delivering against contemporary best practice, guidance and policy. A survey exploring the views and experiences of service users and prescribers on shared and supported decision-making in medication was carried out in West London NHS Trust. Questionnaires were fully co-designed and co-delivered by a group of health professionals and individuals with lived experience. There were 100 responses from service users and 35 from prescribers. There was some good practice where both parties reported good quality conversations concerning dialogic styles, collaborative process, information provided and range of choice offered. However, prescriber's perception of their practice was not always mirrored by service user feedback whose experiences often depended upon the prescriber, the time available or the part of the service. Generally, service user experience fell short of the good practice cited by clinicians though there was noticeable variability. Commitment from organizations and increasing understanding from practitioners are vital in transforming SDM from rhetoric into reality. From our findings a further challenge is to ensure that prescribers and service users have the time, information and tools to implement it consistently.

Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: COVID-19 pandemic has the potential to significantly affect the mental health of healthcare workers (HCWs), who stand in the frontline of this crisis. It is, therefore, an immediate priority to monitor rates of mood, sleep and other mental health issues in order to understand mediating factors and inform tailored interventions. The aim of this review is to synthesize and analyze existing evidence on the prevalence of depression, anxiety and insomnia among HCWs during the Covid-19 outbreak. METHODS: A systematic search of literature databases was conducted up to April 17th, 2020. Two reviewers independently assessed full-text articles according to predefined criteria. Risk of bias for each individual study was assessed and data pooled using random-effects meta-analyses to estimate the prevalence of specific mental health problems. The review protocol is registered in PROSPERO and is available online. FINDINGS: Thirteen studies were included in the analysis with a combined total of 33,062 participants. Anxiety was assessed in 12 studies, with a pooled prevalence of 23·2% and depression in 10 studies, with a prevalence rate of 22·8%. A subgroup analysis revealed gender and occupational differences with female HCPs and nurses exhibiting higher rates of affective symptoms compared to male and medical staff respectively. Finally, insomnia prevalence was estimated at 38·9% across 5 studies. INTERPRETATION: Early evidence suggests that a considerable proportion of HCWs experience mood and sleep disturbances during this outbreak, stressing the need to establish ways to mitigate mental health risks and adjust interventions under pandemic conditions.

Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition.

BACKGROUND: Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD. METHOD: Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method. RESULTS: TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy. CONCLUSIONS: The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review.

INTRODUCTION: Sexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. AIM: To synthesize and analyze the evidence on management of antipsychotic-related sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporated in studies over the past decade. METHODS: EMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline. MAIN OUTCOME MEASURE: The primary outcome measure was any change in sexual function. RESULTS: 6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction. CLINICAL IMPLICATIONS: Due to the lack of high-quality data, no clinical recommendations can be made. STRENGTHS & LIMITATIONS: A comprehensive search strategy was used with an extensive number of relevant search terms including "erectile dysfunction" and newer antipsychotics such as aripiprazole. In light of evidence that prolactin is not a reliable marker for sexual dysfunction, this review focused its inclusion criteria on participants presenting with sexual dysfunction rather than with hyperprolactinemia, which should give its recommendations more validity. However, only 6 RCTs were identified, and results were overall limited by small sample size, brief treatment duration, and the potential for bias. CONCLUSION: Our findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia. Allen K, Baban A, Munjiza J, et al. Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review. J Sex Med 2019;16:1978-1987.

What happens after early intervention? Mapping early intervention in psychosis care pathways in the 12 months after discharge.

AIM: Early intervention services are the established and evidence-based treatment option for individuals with first-episode psychosis. They are time-limited, and care pathways following discharge from these services have had little investigation. We aimed to map care pathways at the end of early intervention treatment to determine common trajectories of care. METHODS: We collected health record data for all individuals treated by early intervention teams in two NHS mental health trusts in England. We collected data on individuals' primary mental healthcare provider for 52 weeks after the end of their treatment and calculated common trajectories of care using sequence analysis. RESULTS: We identified 2224 eligible individuals. For those discharged to primary care we identified four common trajectories: Stable primary care, relapse and return to CMHT, relapse and return to EIP, and discontinuity of care. We also identified four trajectories for those transferred to alternative secondary mental healthcare: Stable secondary care, relapsing secondary care, long-term inpatient and discharged early. The long-term inpatient trajectory (1% of sample) accounted for 29% of all inpatient days in the year follow-up, with relapsing secondary care (2% of sample and 21% of inpatient days), and Relapse and return to CMHT (5% of sample, 15% of inpatient days) the second and third most frequent. CONCLUSIONS: Individuals have common care pathways at the end of early intervention in psychosis treatment. Understanding common individual and service features that lead to poor care pathways could improve care and reduce hospital use.

Prevalence of spontaneous movement disorders (dyskinesia, parkinsonism, akathisia and dystonia) in never-treated patients with chronic and first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-naïve individuals with chronic psychosis and first-episode psychosis (FEP) and gain a more nuanced understanding of factors influencing their presence. METHODS: Several literature databases were systematically searched and screened based on predetermined eligibility criteria. Included articles underwent risk of bias assessment. The prevalence rates of SMDs were calculated using a random-effects model. RESULTS: Out of 711 articles screened, 27 were included in this meta-analysis. The pooled prevalence of spontaneous dyskinesia was 7% (3% FEP and 17% chronic schizophrenia) across 24 studies (95% CI 3 to 11; I2=94%, p<0.01) and 15% for spontaneous parkinsonism (14% FEP and 19% chronic schizophrenia) in 21 studies (95% CI 12 to 20; I2=81%, p<0.01). A meta-regression analysis found a significant positive correlation between age (p<0.05) and duration of untreated psychosis (DUP) (p<0.05) with dyskinesia but not parkinsonism prevalence. Akathisia and dystonia appear to be both less studied and less frequent in occurrence with a pooled prevalence of 4% (95% CI: 3 to 6; I2=0%, p=0.65) for akathisia in eight studies and a mean prevalence of 6% (range 0%-16%) for dystonia in five studies. CONCLUSION: The presence of varying degrees of neurodysfunction in antipsychotic-naïve patients with schizophrenia underscores the need for individualised treatment approaches that consider each patient's unique predisposition and neuromotor profile. Further research is warranted into the role of specific SMDs and risk factors including sex, race and diagnostic variations. PROSPERO REGISTRATION NUMBER: CRD42024501951.

Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series.

Background: Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. Objectives: To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Methods: Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Results: Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. Conclusion: This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.

Care pathways, prescribing practices and treatment outcomes in major depressive disorder and treatment-resistant depression: retrospective, population-based cohort study.

BACKGROUND: Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD). AIMS: To evaluate and compare prescribing patterns, contact with specialist services and treatment outcomes in patients with MDD and TRD. METHOD: This was a retrospective analysis of linked primary and secondary care National Health Service data in the north-west London Discover-NOW data-set. Eligible patients were adults who had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020. RESULTS: A total of 110 406 patients were included, comprising 101 333 (92%) with MDD and 9073 (8%) with TRD. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol or substance misuse (all P < 0.0001). Citalopram, sertraline, fluoxetine and mirtazapine accounted for 83% of MDD and 71% of TRD prescriptions. Use of antidepressant switching (1% MDD, 7% TRD) and combination therapy (1%, 5%) was rare, whereas augmentation occurred more frequently in the TRD group (4%, 35%). Remission was recorded in 42 348 (42%) patients with MDD and 1188 (13%) with TRD (P < 0.0001), whereas relapse was seen in 20 970 (21%) and 4923 (54%), respectively (P < 0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 (s.d. 33.6) months for MDD and 41.5 (s.d. 32.0) months for TRD (P < 0.0001). CONCLUSIONS: There appears to be a considerable difference between treatment guidelines for depression and TRD and the reality of clinical practice. Long-term treatment with single antidepressants, poor remission, and high relapse rates among patients in primary care highlight the need to optimise treatment pathways and access to newer therapies.

Interventions to improve the sleep quality of adults with personality disorder: A systematic review.

Poor quality sleep is common for people who have a diagnosis of personality disorder (PD). Core cognitive and behavioral features of PD may cause and perpetuate poor sleep, but to date, no review has collated the evidence on the efficacy of interventions to improve sleep quality for people with PD. Structured searches for interventional studies among adults with PD and reporting validated measures of sleep quality were conducted up to November 2022 in multiple databases. Single-case reports were excluded. Study quality was assessed with standardized risk of bias tools. Unreported data was sought systematically from authors. This review was pre-registered with an international prospective register of systematic reviews (PROSPERO) (CRD42021282105). Of the 3503 identified studies, nine met inclusion criteria, representing a range of psychological, pharmaceutical, and other interventions and outcome measures. Meta-analytic methods were not feasible because of the serious risk of bias in all studies, and results were therefore synthesized narratively. There is limited and low-quality evidence of the effects of a variety of interventions to improve the sleep quality of people living with PD. Further research might consider specifically including people diagnosed with PD in trials of sleep interventions and using sleep outcome measures in trials of established PD treatments.

Rehabilitation Is Associated With Improvements in Post-COVID-19 Sequelae.

BACKGROUND: Post-COVID-19 syndrome has affected millions of people, with rehabilitation being at the center of non-pharmacologic care. However, numerous published studies show conflicting results due to, among other factors, considerable variation in subject characteristics. Currently, the effects of age, sex, time of implementation, and prior disease severity on the outcomes of a supervised rehabilitation program after COVID-19 remain unknown. METHODS: This was a non-randomized case-control study. Subjects with post-COVID-19 sequelae were enrolled. Among study participants, those who could attend an 8-week, supervised rehabilitation program composed the intervention group, whereas those who couldn't the control group. Measurements were collected at baseline and 8 weeks thereafter. RESULTS: Study groups (N = 119) had similar baseline measurements. Participation in rehabilitation (n = 47) was associated with clinically important improvements in the 6-min walk test (6MWT) distance, adjusted (for potential confounders) odds ratio (AOR) 4.56 (95% CI 1.95-10.66); 1-min sit-to-stand test, AOR 4.64 (1.88-11.48); Short Physical Performance Battery, AOR 7.93 (2.82-22.26); health-related quality of life (HRQOL) 5-level EuroQol-5D (Visual Analog Scale), AOR 3.12 (1.37-7.08); Montreal Cognitive Assessment, AOR 6.25 (2.16-18.04); International Physical Activity Questionnaire, AOR 3.63 (1.53-8.59); Fatigue Severity Scale, AOR 4.07 (1.51-10.98); Chalder Fatigue Scale (bimodal score), AOR 3.33 (1.45-7.67); Modified Medical Research Council dyspnea scale (mMRC), AOR 4.43 (1.83-10.74); Post-COVID-19 Functional Scale (PCFS), AOR 3.46 (1.51-7.95); and COPD Assessment Test, AOR 7.40 (2.92-18.75). Time from disease onset was marginally associated only with 6MWT distance, AOR 0.99 (0.99-1.00). Prior hospitalization was associated with clinically important improvements in the mMRC dyspnea scale, AOR 3.50 (1.06-11.51); and PCFS, AOR 3.42 (1.16-10.06). Age, sex, and ICU admission were not associated with the results of any of the aforementioned tests/grading scales. CONCLUSIONS: In this non-randomized, case-control study, post-COVID-19 rehabilitation was associated with improvements in physical function, activity, HRQOL, respiratory symptoms, fatigue, and cognitive impairment. These associations were observed independently of timing of rehabilitation, age, sex, prior hospitalization, and ICU admission.

Switching from Monthly to Three-Monthly Long-Acting Injectable Paliperidone: A Survey on Subjective Satisfaction and Safety.

Introduction: Poor adherence to antipsychotic medication is common in the treatment of schizophrenia and other psychotic disorders. Paliperidone palmitate 3-monthly (PP3M) is the first long-acting injectable (LAI) antipsychotic to allow for only four medication administrations per year, and although there is sufficient information available about the clinical effects, there is relatively limited insight into the subjective experience of people with lived experience. Methods: This descriptive, cross-sectional survey explored patient's satisfaction and perspectives on the advantages and disadvantages of switching from monthly to 3-monthly paliperidone while also reporting on perceived levels of safety with regard to the reducing dose regimen during the Covid-19 pandemic. Information on discontinuation and hospitalisation rates at one year was also collected from the electronic records. Results: Of the 46 patients included in the study, the vast majority reported feeling satisfied (89.2%) and safer (93.5%) after switching to the three-monthly formulation. Participants highlighted several advantages of changing to PP3M, most notably convenience (93.5%), improved quality of life (58.7%), decreased stigma (39.1%) and better adherence (28.3%). Furthermore, 93.5% of respondents experienced no disadvantages, while 6.5% described worsening side effects or symptoms. In fact, only one patient discontinued PP3M at one year with the overall number of hospitalisations also reducing in the same period compared to the year before switching. Discussion: Our findings add to the small, but growing, body of evidence supporting patient satisfaction and acceptance with the use of PP3M and may reinforce the use of less frequent LAIs in clinical practice to enhance individual experience and treatment persistence and decrease levels of stigmatisation.