bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Burnout Among Doctors in a Tertiary General Hospital
Authors: Lim Leslie , Loh Louis , Chan Yiong-Huak , Eng Leonard , Fam Johnson 
Published: August 2024

AimsTo study the risk factors for burnout among doctors in a tertiary general hospital in Singapore. We hypothesized that burnout would be associated with singles, young age, females, foreign born staff who had recently moved to this country unaccompanied by family, and those showing less resilience. We hypothesised perceived support and satisfaction with leisure would mitigate against burnout.MethodsAn anonymised survey was carried out, with questionnaires sent to all staff via email. Survey instruments included the Oldenburg Burnout Inventory, Connor Davidson Resilience Scale, Brief Form of Perceived Social Support Questionnaire, Patient Health Questionnaire-4 items (PHQ-4), Leisure Time Satisfaction Survey and the Demand Control Support Questionnaire (DCSQ). Descriptive statistics for normally-distributed numerical variables were presented as mean (SD or standard deviation), and for categorical variables, median and n (%). One-way ANOVA was performed to determine differences in total burnout scores across categorical variables and simple linear regression was used to assess for binary and numerical outcomes in terms of resilience, PHQ, DSCQ, satisfaction with leisure time and perceived social support, with significance set as p < 0.05.ResultsA total of 129 doctors responded to the survey. Over half were male, and nearly 70% were married. Nearly half were below age 40 and only about 5% had no immediate family living in Singapore.Burnout was associated with young age (p < 0.004) and those with anxiety 2.39 (2.13 to 2.64) p = 0.038, and depressive symptoms 2.71 (2.44 to 2.97) p < 0.001. Psychological demand was positively associated with burnout (1.52 (1.32 to 1.71) p < 0.001; whereas decision latitude −0.69 (−0.85 to −0.52), social support at work −1.35 (−1.49 to −1.21), and high resilience −0.56 (−0.63 to −0.48), were negatively associated (all p < 0.001).Satisfaction with leisure time was negatively correlated with burnout (p < 0.001). Contrary to hypothesis, singlehood, gender, overseas staff recently joined with no accompanying family were not associated with burnout (p > 0.05). In addition, perceived social support from outside work did not mitigate against burnout (p > 0.05).ConclusionYoung age, anxiety and depression, and psychological demands were risk factors, whereas resilience, decision latitude, satisfaction with leisure, and social support at work were protective factors against burnout. Reducing workload, improving work schedules, promoting self-management, teaching physical, mental, and emotional self-care, and other stress management activities are among the effective techniques shown to reduce burnout. Interventions should be made available for all staff, but specifically focusing on those at greatest risk.
Modelling Clozapine Levels to Identify Safe Titration Targets and a Method for Precise Dose Adjustment
Authors: Meyer Zeryab , Simpson Gemma , Drake Richard J 
Published: August 2024

AimsA precision medicine approach to clozapine dosing aims to personalise it in two ways: i) during titration, and ii) for succeeding dose adjustments. This requires valid models of dose/concentration relationships, but cross-sectional models suffer from population-level artefacts and individual problems due to poor adherence or stopping smoking. Longitudinal data sets from two mental health trusts allowed poor adherence and smoking cessation to be identified. We then modelled dose/concentration relationships to construct personalised targets for i) and ii).MethodsDemographics and co-prescribed medication were recorded for 137 patients from Greater Manchester Mental Health (GMMH) Trust who had two or more successive plasma levels and doses from 2016–2018. 412 patients from Pennine Care Foundation Trust (PCFT) who had successive plasma levels and doses from 2009–2023 were also recorded. In each sample, adherent patients (88 from GMMH and 371 from PCFT) were identified after excluding: > two-fold variation between blood samples in clozapine/norclozapine ratios, > two-fold variation in dose/concentration ratios, a clozapine/norclozapine ratio > 3, or a dose/concentration ratio > two standard deviations from the sample mean. Those whose smoking status (smoker vs non-smoker) changed between samples were excluded.To identify i) titration targets, we used raw data in first samples (checked with logistic regression) to identify dose thresholds which produced most levels above 0.35 μg/ml (therapeutic) and no levels greater than 1 μg/ml (toxic). To model ii) effective dose adjustment, we used the equation Dt = Dc(Ct/Cc) to identify the most effective dose for the second samples. Dt was target dose, Dc current dose, Ct target level (0.45 μg/ml), and Cc current level.ResultsFirst sample dose/concentration ratio in adherent patients correlated r > 0.75 with second samples’ dose/concentration. >84% of plasma levels were within 20% of the mean across both samples.
i.The GMMH dataset titration targets were 325 mg, 300 mg, 225 mg, and 175 mg daily for male smokers, female smokers, male non-smokers, and female non-smokers, respectively. In PCFT, data suggested corresponding targets of 375 mg, 325 mg, 225 mg and 175 mg. Targets avoided toxicity and gave therapeutic levels in > 50% of cases.ii.Target dose, ascertained using the equation, and actual second dose were compared: in adherent cases, toxicity only occurred when actual doses were 1.5-fold greater than target dose, and above target all plasma levels exceeded 0.35 μg/ml in GMMH. PCFT data appeared similar.ConclusionRelatively safe and effective titration targets for smokers and non-smokers from both sexes were identified. A simple equation would improve precision and effectiveness of dose adjustment thereafter.
Cognitive Behavioural Therapy Versus Psychodynamic Therapy for Medically Unexplained Symptoms: A Retrospective Study of Healthcare Utilisation and Cost Analysis
Authors: Naylor Rory 
Published: August 2024

AimsPatients experiencing Medically Unexplained Symptoms (MUS) are some of the costliest in both primary and secondary care. Psychotherapy is one of the most efficacious ways of treating them although the most superior modality is unclear. Cognitive Behavioural Therapy (CBT) has the greatest evidence base, but a growing number of studies have investigated the role of Psychodynamic Psychotherapy (PPT). This is the first study to compare the two modalities concerning their impact on healthcare utilisation and cost to the NHS.MethodsPatients referred to the Oxford Community Psychological Medicine Service in 2021 and who went on to complete a course of psychotherapy for MUS were included. 78 patients were referred, 66 patients were assessed, 16 patients began treatment and 9 patients completed treatment. 4 received CBT and 5 received PPT based on a ‘best fit’ assessment. Their healthcare utilisation (GP appointments, health investigations, A&E attendances, inpatient admissions and outpatient appointments) was assessed during the 6 months prior to their initial assessment and compared with the 6 months after therapy had ended using data from ‘Health Information Exchange’.ResultsOverall, psychotherapy reduced primary care use but our data was insufficiently powered for this to be statistically significant. There was a significant reduction in outpatient appointments after psychotherapy, mostly representing mental health consults.Significant differences between pre-therapy and post-therapy were only observed for the number of health investigations in the PPT group which, surprisingly, increased with a large effect size (d = 1.19 95% CI 1.12–2.88, P = 0.03). The same trend towards increased utilisation were observed for every outcome measure in PPT besides outpatient appointments. Conversely, all outcome measures showed an improvement after CBT apart from the number of health investigations which marginally increased.CBT significantly decreased GP appointments at 6 months follow-up compared with PPT with a large effect size (η2 = 0.5, p < 0.05). A similar trend was seen for total cost (η2 = 0.5, p < 0.06) with each PPT patient costing £790 more on average than their CBT counterparts during the 6 months after therapy.ConclusionWhilst CBT appears to be efficacious in the short-term, PPT caused significantly increased healthcare utilisation compared with CBT in the 6 months after therapy. This aligns with similar studies that demonstrate a ‘sleeper effect’ in which patients who receive PPT, but not CBT, deteriorate before improving over long-term follow-up.Additional research is needed to correlate this data with symptoms and capture the long-term benefits of these psychotherapies for MUS.
The Effects of Developmental Stress on Dopaminergic Function in Adulthood: A Systematic Review and Meta-Analysis
Authors: Noar Alexander , Chapman George , Chang Tinya , Payne-Gill James , Bloomfield Michael 
Published: August 2024

AimsExposure to traumatic experiences during childhood and adolescence is a significant risk factor for the development of psychiatric disorders in adulthood. An estimated 50% of the worldwide incidence of depression and anxiety can be attributed to childhood maltreatment (Li et al., 2016). In addition, approximately one-third of psychotic experiences are attributable to a history of developmental trauma (McGrath et al., 2017). It is thought that long-lasting, trauma-induced adaptive changes in neurobiological function may lead to a predisposition towards pathophysiology (McCrory and Viding, 2015). However, the precise mechanisms through which developmental trauma exposure alters brain function on cellular and circuit levels remain poorly elucidated.MethodsA systematic literature search and meta-analysis was performed to establish how dopaminergic functioning in adulthood is affected by developmental stress in rodents. Three databases, Medline®, Embase®, and PsycINFO®, were systematically searched initially on 2nd December 2023. Terms for three superordinate concepts (‘childhood’ terms, ‘trauma’ terms, and ‘dopamine’ terms) were combined. Cohen's d statistic was used for effect sizes. This protocol is pre-registered on PROSPERO® (ID: CRD42018106382).ResultsA total of 104 studies met our inclusion criteria. Meta-analysis indicated that developmental stress exposure leads to complex and long-lasting effects in basal and post-amphetamine extracellular dopamine concentrations in the medial prefrontal cortex, amygdala, and nucleus accumbens. In addition, there is a significant downregulation of D1 receptors and upregulation of D2 receptors in prefrontal and striatal regions involved in threat and reward processing. Effect sizes ranged from 0.36 to 1.55.ConclusionThese findings strongly suggest that dopaminergic dysfunction is a mechanistic link between developmental trauma and vulnerability towards mental illness in adulthood.
Modelling Co-Occurring Mental Health Conditions Among Autistic Individuals Using Polygenic Scores
Authors: Okewole Adeniran , Bourque Vincent-Raphael , Jacquemont Sebastien , Warrier Varun , Baron-Cohen Simon 
Published: August 2024

AimsThis study investigated the relationship between common genetic variation and co-occurring mental health conditions among autistic individuals.MethodsThe study was conducted with the Simons Foundation Powering Autism Research (SPARK) dataset, V9 release, and included probands [n = 17,582] with confirmed diagnosis of autism, who were also in the SPARK iWES1 array genotyping dataset. Six co-occurring mental health conditions (attention deficit hyperactivity disorder or ADHD, bipolar disorder, depression, schizophrenia, anxiety disorder and disruptive behaviour disorders) were analysed. Polygenic scores (PRS) were generated with PRScs software, using summary statistics from the most recent genome wide association studies (GWAS) for autism, ADHD, schizophrenia, bipolar disorder, depression, anxiety, neuroticism, p-factor, intelligence, educational attainment and hair colour (negative control). General linear models (GLM) and Cox proportional hazards models were computed, with age at registration, sex, cognitive impairment and genetic principal components included in both sets of models. Multiple testing correction was done using the Benjamini-Yekutieli method. Results were calculated using odds ratios (OR), 95% Confidence Intervals (CI) and corrected p values (p).ResultsThere were similar patterns of association and interaction for both GLMs and Cox models. Polygenic scores for educational attainment were significantly lower for those with co-occurring ADHD (GLM: OR=8.85E-01, 95% CI=8.48e-01–9.23e-01, p = 2.91E-07; Cox: OR=8.94E-01, 95% CI=8.66e-01–9.22e-01, p = 4.76E-11), bipolar disorder (GLM: OR=7.45E-01, 95% CI=6.54e-01–8.49e-01, p = 2.40E-04; Cox: OR=7.25E-01, 95% CI=6.39e-01–8.23e-01, p = 3.96E-05), depression (GLM: OR=8.63E-01, 95% CI=8.04e-01–9.26e-01, p = 5.13E-04; Cox: OR=8.56E-01, 95% CI=8.03e-01–9.12e-01, p = 2.80E-05), schizophrenia (GLM: OR=6.94E-01, 95% CI=5.71e-01–8.42e-01, p = 3.99E-03; Cox: OR=6.67E-01, 95% CI=5.52e-01–8.05e-01, p = 1.41E-03), anxiety disorder (GLM: OR=8.77E-01, 95% CI=8.37e-01–9.20e-01, p = 9.88E-07; Cox: OR=8.81E-01, 95% CI=8.49e-01–9.15e-01, p = 1.46E-09) and disruptive behaviour disorders (GLM: OR=7.10E-01, 95% CI=6.63e-01–7.60e-01, p = 3.22E-21; Cox: OR=7.10E-01, 95% CI=6.67e-01–7.57e-01, p = 1.35E-24).ConclusionPolygenic scores for educational attainment were associated with the co-occurrence of several mental health conditions among autistic individuals.
How Are Inpatient Psychiatric Ward Rounds Understood in Research Literature? A Scoping Review
Authors: Williams Benjamin , Olagunju Oluwatomilola , Richardson Siobhan , Jameson Georgia 
Published: August 2024

AimsWard rounds are complex clinical interactions crucial in delivering high-quality, safe, and timely patient care. They serve as a platform for the multidisciplinary team to collaboratively assess a patient's condition and actively involve the patient and their caregivers in shared decision-making to formulate a care plan. Ward rounds involve an intersection of factors worthy of consideration separate from the wider literature on inpatient experience and multidisciplinary team meetings. With this review our primary aim is to systematically identify what methods and perspectives researchers are using to understand ward rounds.MethodsThe databases searched were Medline, CINAHL, British Nursing Index, PsychInfo, and ASSIA as well as reference and citation checking. The search terms used were psychiatr* AND (ward round OR “multi disciplinary team meeting” OR “clinical team meeting”). Studies were included if they were peer reviewed, included primary research on psychiatric inpatient ward rounds in which patients are participants with no restriction on the type of ward or hospital, patient group, country or methodology.Results224 records were retrieved and screened from the database search and 10 from other sources. 35 full texts were reviewed for eligibility and 26 included in the review. 16 studies had no particular theoretical perspective, 2 were constructivist, 2 critical realist, 2 lean methodology, 1 systems research, 1 phenomenological, 1 trauma informed and 1 critical theory. 9 focussed on patient experience, 5 ward round structure, 3 on power relationships, 3 on efficiency, 2 on shared decision making and 4 had a unique focus. Though often not explicit, critical theory influenced discussion of power is common in papers focused on patient experience and ward round structure. Cross-sectional surveys, interviews, focus groups and audit cycles were the most common methods. Key themes which emerge are anxiety provoked by ward rounds, preparation and communication, and the negotiation of power structures. Key tensions identified include being multidisciplinary versus overcrowding, efficiency versus personalisation and reliability versus responsiveness.ConclusionFor a central part of inpatient psychiatric practice there is a limited range of research on psychiatric ward rounds. The influence of critical theories’ focus on power was widespread with limited representation of other theoretical perspectives and concerns. There was no research using experimental methods, but there was some implementation research. Key tensions are highlighted which services may wish to consider when revisiting ways of working on inpatient psychiatric wards.
An Estimation of the Numbers of Patients Suitable for Lecanemab Treatment for Alzheimer's Pathology Within Mid and South Essex
Authors: Shanley Ivan , Pranay Piyush , Dilip Chitra , Hill Christopher St , Sebastian Feena 
Published: August 2024

AimsThis paper sought to estimate the number of potential candidates per year, within the boundaries of the Mid and South Essex Integrated Care System, for the receipt of Lecanemab, a novel treatment of Alzheimer's pathology.MethodsOne of the four memory assessment services within the region was selected at random, following which all referrals to that service in January and February 2023 were retrieved from the electronic patient record system (n = 45). These records were then screened to assess whether the patient met the criteria for treatment with Lecanemab. The inclusion and exclusion criteria from the original CLARITY-AD phase 3 clinical trial (van Dyck et al., 2022) were combined with those of the Appropriate Use Recommendations released by the Alzheimer's Disease and Related Disorders Therapeutics Work Group (Cummings et al., 2023)1,2. Patients could not be identified as certainly suitable for treatment, but simply as potential candidates, as current practice does not include all the necessary investigations to receive the new drug, for example undergoing amyloid PET or CSF testing.Results11 of 45 referrals were potential candidates for novel therapeutics (24.4%). Of the 11, 3 were diagnosed with Alzheimer's disease (27%), and 8 with Mild Cognitive Impairment (73%). 8 were male, 3 female, with a mean age of 78 years (range 70 to 87). The mean score on the Addenbrooke's Cognitive Examination III was 82/100. Two patients had co-morbid mental illness, both mixed anxiety and depression, currently in remission. Extrapolating from this rate of eligibility for treatment, it is suggested that approximately 260 patients per year would be eligible for Lecanemab treatment within Mid and South Essex.ConclusionThis paper estimates that approximately 260 patients per year would be eligible for Lecanemab treatment within Mid and South Essex based on the inclusion and exclusion criteria stated above. This estimate is given with caution, particularly as neither amyloid PET nor CSF testing was performed, and it is still not clear what other stipulations may be made by the UK regulatory bodies (for example the degree of vascular pathology permitted on neuroimaging). This paper does however provide a useful, early estimate of eligibility in order to facilitate planning for potential treatment pathways.
CONNEX, a Phase III Randomized Trial Program Assessing Efficacy and Safety of Iclepertin in Schizophrenia: Recruitment and Baseline Characteristics
Authors: Blahova Zuzana , Ikezawa Satoru , Falkai Peter , Krystal John H. , Rangan Tarun 
Published: August 2024

AimsGlutamatergic signalling deficits contribute to the neuropathology of cognitive symptoms in schizophrenia. Iclepertin (BI 425809), a glycine transporter-1 inhibitor, enhances N-methyl-D-aspartate receptor signalling in the brain by increasing synaptic levels of its co-agonist glycine. The Phase III CONNEX programme aims to assess the efficacy, safety and tolerability of iclepertin in improving cognition and functioning in schizophrenia.MethodsCONNEX includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia from multiple centres across 41 countries in Asia, North and South America, Europe, and Asia Pacific Region (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ~586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug; ≥35 days on current dose before treatment), who have functional impairment in day-to-day activities and interact ≥1 hour/week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, or receiving cognitive remediation therapy ≤12 weeks before screening will be excluded. Patients will be randomised 1:1 to once-daily oral iclepertin 10 mg (n = 293) or placebo (n = 293) for 26 weeks. Primary endpoint: change from baseline (CfB) in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) overall composite T-score. Key secondary endpoints: CfB in Schizophrenia Cognition Rating Scale (SCoRS) total score and adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT).ResultsTrial completion is expected in Q1 2025. By 31/01/2024, there have been 811, 699 and 655 patients screened, 533, 474 and 458 randomised, and 320, 299 and 281 who have completed the trial medication for CONNEX-1, -2 and -3, respectively. Most patients are male (CONNEX-1: 69.3%, CONNEX-2: 69.0%, CONNEX-3: 63.3%) with similar age (mean [standard deviation; SD]) (CONNEX-1: 34.0 [8.9], CONNEX-2: 35.9 [8.4], CONNEX-3: 34.0 [8.8] years). For CONNEX-1, -2 and -3, mean (SD) duration of illness is 10.6 (8.3), 12.2 (7.9) and 9.6 (7.6) years and duration of previous schizophrenia treatment is 3.9 (4.6), 4.5 (4.9) and 3.3 (4.4) years. Baseline mean (SD) MCCB overall composite T-score (1: 28.4 [13.7], 2: 27.3 [13.8], 3: 29.7 [13.7]), SCoRS total score (1: 40.5 [11.1], 2: 39.9 [9.7], 3: 38.0 [10.0]) and VRFCAT adjusted total time T-score (1: 29.6 [22.3], 2: 30.7 [20.8], 3: 33.6 [18.1]) were similar across trials.ConclusionIf successful, CONNEX will provide evidence for iclepertin as the first efficacious medication addressing cognitive impairments in schizophrenia.Studies funded by Boehringer Ingelheim.
Impact of Covid-19 on Referrals to Paediatric Liaison Psychiatry at Children's Health Ireland (CHI) at Crumlin as the Pandemic Moved to Endemic Status
Authors: Sun Bohan , Adamis Dimitrios , McNicholas Fiona 
Published: August 2024

AimsRates of acute mental health presentations in youth were rising pre-pandemic internationally. Longitudinal studies following Covid-19 attest to ongoing deterioration in youth mental health, recognising adverse unintended consequences following public health restrictions.This study aimed to examine whether the initial reported post-Covid-19 increase in mental health presentations persisted following the reclassification of Covid-19 to endemic status, which was accompanied by removal of most restrictions.MethodsAll referrals to paediatric liaison psychiatry (PLP) between Jan 2018–Dec 2022 in a Dublin tertiary children's hospital were included in the study. An interrupted time series analysis was conducted examining referrals with respect to different phases of Covid-19 and application of public health restrictions.Results1,385 referrals to PLP were received over the 5-year study time-period. There was a significant decrease in PLP referrals immediately post Covid-19, following a significant and sustained increase as the pandemic progressed. Public health restriction phases had a unique effect on those presenting with suicidal ideation, with a significant increase in the number of referrals received. There was no effect of restrictions on other clinical profiles.ConclusionIncreased referrals for youth with mental health difficulties, reported during the Covid-19 pandemic, persisted into the early endemic stage, after Covid-19 public health restriction have ceased. Potential impacts of restrictions on referrals of youth with suicidal ideation require further study. Investment in child and adolescent mental health services remain a priority, and future pandemic responses need to examine unintended consequences of any enforced public health measure.