bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Is the Evidence for Using Anti-Epileptic Drugs to Treat Agitation and Irritability in Huntington's Disease?
Authors: Leong Kok Keong , Paramlall Mark 
Published: June 2022

AimsBackground: Huntington's disease (HD), due to the pathological expansion of CAG trinucleotide repeats within the Huntington's gene on chromosome 4p (1), is an autosomal dominant progressive neurodegenerative disease with motor, cognitive and neuropsychiatric symptoms that includes irritability and agitation in an estimated 38–73% of HD patients (2) which is characterized by impatience and a tendency to become angry in response to minimal provocation. Expert consensus recommends implementation of environmental and behavioural strategies then commencing treatment with SSRI's, Neuroleptics or Anti-Epileptic Drugs (AED) (3). No previous papers, to our knowledge, have examined the newest antiepileptic agents or have identified the most efficacious antiepileptics for this use. Aim: We present a review of the literature describing antiepileptic treatments for agitation and irritability in HD focusing on identification of the most efficacious antiepileptics and the role of newer antiepileptic agents for this use.MethodsA search in the main database sources (EMBASE, MEDLINE, Allied and Complementary medicine) was performed in order to obtain a comprehensive evaluation of available antiepileptic psychopharmacological treatments in HD for agitation and irritability.ResultsAntiepileptic (AED) agents described in consensus statements and case studies have included sodium valproate, carbamazepine and lamotrigine, which work by inhibition of voltage gated Na and Ca channels, and are often combined with antipsychotic agents for improvement of pathological mood swings and irritability. However, none of the papers identified were Level III or better.ConclusionNo specific mood stabilizing antiepileptic psychopharmacological treatment of the Psychiatric symptoms of irritability and agitation in HD was identified. Overall, the use of AED have weak evidence base with no quantifiable outcome measures, such as such as the Disruptive or Aggressive Behavior behavioural subscale of the Unified Huntington's Disease Rating Scale or the Neuropsychiatric Inventory, indicating improvement of symptoms identified. Surveys and expert opinions were based on their personal knowledge of the HD populations and the selection of the experts surveyed was not systematic which could influence the practice pattern results. The review indicates a pressing need for treatment studies to determine which psychopharmacological and behavioral treatments are most efficacious.
Haematological Monitoring in Clozapine Use: Blood Best Sampled in the Afternoon?
Authors: Ade-Dosumu Adedoyin , O'Connell Henry 
Published: June 2022

AimsClozapine is an atypical antipsychotic used in the management of Treatment-Resistant Schizophrenia (TRS). Despite its efficacy, Clozapine is associated with rare but clinically important haematological side effects of neutropenia and agranulocytosis, thus warranting regular monitoring of full blood count (FBC) white blood count (WBC) and neutrophil count (NC).Clozaril Patient Monitoring service (CPMS) supervises the prescribing of Clozapine and haematological testing for patients. Amber and Red alerts are issued by the CPMS when WBC and NC values fall below specified levels, Clozapine treatment is either suspended or discontinued completely.MethodsWe present a case of 35-year-old Caucasian lady with a history of schizophrenia who was maintained on Clozapine treatment for 10 years and whose Clozapine was necessarily stopped because of red alerts. This lead to a significant deterioration in her mental state and level of functioning necessitating a prolonged hospital admission.Results•Detailed retrospective review of this patient's CPMS results over a 2-year period identified consistently higher levels of WBC and NC, when the blood tests were conducted in the afternoon compared to mornings.•Literature review supported the phenomenon of a diurnal variation of WBC and NC levels in a proportion of patients prescribed Clozapine.•With clear knowledge of this patient's diurnal trends in WBC and NC count, it was possible to liaise with CPMS and restart her Clozapine treatment, leading to a significant improvement in her mental state and level of functioning.Conclusion•We recommend that clinicians consider this phenomenon of diurnal variation in blood parameters in patients with frequent amber and red alert results who are at risk of having their Clozapine medication discontinued.•Close collaboration with CPMS and haematological advice may lead to a more nuanced approach to blood sampling, whereby afternoon samples are used in certain at-risk patients.
Clinical Audit of Clozapine Prescribing Practice and Monitoring Process in an Australian Community Mental Health Service
Authors: Fernando Tharushi , Bhandarkar Ritesh , Meadows Graham 
Published: June 2022

AimsClozapine, a well-established treatment of choice for treatment-resistant schizophrenia is known to reduce suicidality, lessen the risk of tardive dyskinesia and reduce relapse risk. It contributes to a higher quality of life by reducing cognitive clouding. Patients taking Clozapine have improved social and work functioning. But Clozapine's significant side effects require regular, intense monitoring to minimize mortality and morbidity. To improve current practice of clozapine prescribing and monitoring, a systematic audit of service practices against guidelines of local hospital / Monash Health Clozapine patient management guidelines and the Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines will identify any deficits and inform measures to overcome them.MethodsAn audit was conducted to compare the current clozapine prescribing practice and monitoring process compared with local hospital / Monash Health Clozapine patient management guidelines and RANZCP clinical practice guidelines among clozapine prescribed patients in an Australian community mental health service.ResultsMedical records of thirty-three eligible adult patients on clozapine were audited. All the patients were prescribed dosages within the recommended daily clozapine range. Clozapine was used for appropriate indications (treatment of treatment resistant-schizophrenia or schizoaffective disorder). Of the 33 patients, clozapine level was subtherapeutic on 54.5% of patients. 54.5% of patients were on an adjunct psychotropic with clozapine. Aripiprazole and sodium valproate were used by eight patients each, and nine patients were identified using selective serotonin reuptake inhibitors. The most common side effect was hypersalivation (57.6%), followed by weight gain (39.4%), sedation (21.2%) and constipation (12.1%). Monthly weight monitoring, physical examination, medical officer monthly review and full blood examination, at 97% compliance met these standards. However, monitoring of Body Mass Index (BMI) (66.7%) and six-monthly consultant reviews (42.4%) showed poor compliance (<70%) with the standards. Most metabolic blood investigations were in moderate compliance (70–90%) except for relatively high compliance for lipid profile (90.1%). Monitoring cardiac functions by echocardiogram were only 75.8% met the standard.ConclusionMost patients in this clinic receive recommended monthly monitoring practice but for BMI monitoring, six-monthly consultant review, most blood investigations and annual or 2 yearly echocardiogram findings indicated need for improvement. Polypharmacy of psychotropics increases the side effect burden and further increases the need to closely monitor the physical health and prescriptions of this cohort of patients. The next stage of this project will involve a codesign approach to developing a response to these findings that will be outlined here.
Primary Care Referrals of Suspected Eating Disorders in Children and Young People in Greater Manchester Audit
Authors: Geers Benjamin , Ochando David 
Published: June 2022

AimsCurrent NICE guidance states that Children and Young People (CYP) with suspected Eating Disorders (EDs) should be immediately referred to specialist services on their first presentation to primary care. This audit assessed whether these standards were being met across Greater Manchester and what general practitioners felt would be helpful in supporting them to correctly refer patients. Aim 1: Analyse information from referral forms on all patients referred to Manchester Foundation Trust Community Eating Disorders Service (MFT-CEDS) from primary care between 17th December 2020 – 17th June 2021. Aim 2: Gain insight into how confident GPs in Greater Manchester feel identifying suspected EDs in CYP, their knowledge of guidelines regarding referral, and how they would like to be supported to improve referrals of suspected CYP-ED.MethodsQuantitative data on all primary care referrals made between 17th December 2020–17th June 2021 were analysed. Referrals were classified as correct if they were made both immediately and directly to the correct service. Subgroup analysis of data by geographic region of Greater Manchester was also undertaken. Qualitative data were collected through a survey which was sent to General Practitioners across Greater Manchester. The survey assessed knowledge of current guidelines and views on what training materials could be helpful to improve the referral process.ResultsA total of 69 patients were referred to MFT-CEDS by their GP between 17th December 2020 and 17th June 2021. 35% of GP referrals to MFT-CEDS were documented as being made correctly as per current guidelines. 43.5% of all referrals were not initially made to MFT-CEDS. 58% of referrals were documented as being made immediately. North and South Manchester had the lowest rates of correct referrals of 10% and 8% respectively. There were 10 survey respondents, of which the majority did not know current referral guidelines and did not feel confident in identifying suspected Eating Disorders in CYP.ConclusionThe majority of primary care referrals of CYP with suspected eating disorders to MFT-CEDS were not made in line with current NICE guidance.The following recommendations were made based on the findings of this audit:1) Create an information document and video regarding identification and referral guidelines for suspected EDs in CYP, 2) Design an easy-to-use referral template for GPs, 3) Conduct interviews with GPs working in North and South Manchester to help identify what additional support they need, 4) Re-audit referral data once quality improvement measures have been in place for 6 months.
Training Non-Medical Staff for SARS-CoV-2 Swab Collection on a Psychiatric Old Age Ward
Authors: Legg Joanna , Ouabbou Sophie , Hay Susan 
Published: June 2022

AimsIn the second half of 2020 patients admitted to Highgate Mental Health Centre had to isolate in their rooms until a negative SARS-CoV-2 test result was obtained. This was stressful for both patients, who were unwell in their mental state, and staff. Swabs for PCR testing were only being collected by junior doctors which meant that out of hours, this responsibility would fall exclusively upon the duty doctor. There were often significant delays to obtain a sample. We decided to train non-medical staff on an old age ward so that the responsibility of collecting samples could be shared with nurses and healthcare assistants.MethodsIn November 2020 we held one training session with several members of staff from our ward. In the following days we did one to one training sessions with the members of staff who, due to their shifts, were not available for the original training session. We excluded admissions that happened prior to SARS-CoV-2 being mandatory, those where the patient refused to be swabbed, and those patients who were transferred from another institution already with a pre-admission swab.ResultsThere were 37 admissions, of which we included 30 based on the exclusion criteria. 17 admissions occurred prior to training and 13 after the training sessions. Prior to training, it took 1.059 days to obtain a sample and it took 0.846 days after the training sessions.ConclusionProviding a training session to enable nurses and healthcare assistants to take samples for SARS-CoV-2 testing reduced the amount of time between admission and obtaining a swab sample. We therefore shortened the first step of the process that leads to obtaining a negative result and enable a patient to come out of isolation.
A Quality Improvement Project (QI) on Screening for Rapid Eye Movement Sleep Behaviour Disorder (RBD) in Patients Referred to Trafford Memory Assessment and Treatment Service (MATS), Part of Greater Manchester Mental Health Trust (GMMH)
Authors: Moir Rachel , Pye-Jones Ruth , Sindhi Amit , Benjamin Boben 
Published: June 2022

AimsLewy Body Dementia (LBD) is predicted to be under-diagnosed in the general population. RBD is one of the four core clinical criteria for the diagnosis of LBD. Longitudinal studies of RBD show strong association with LBD, so there is potential for early identification of LBD and subsequent management. We aimed to screen 100% of patients referred to Trafford MATS for RBD.MethodsWe performed three Plan-Do-Study-Act (PDSA) cycles; in the first cycle we introduced a validated RBD screening question, from the DIAMOND-Lewy study, to the initial memory assessment proforma. This asked ‘Have you ever been told that you “act out your dreams” while sleeping (punched or flailed arms in the air, shouted or screamed)?’In the second PDSA cycle, we delivered a RBD and LBD educational package to the specialist memory nurses who undertake the initial assessments. In the third PDSA cycle reminders were sent to the team to use the new assessment proforma.We collated data from patients who had undergone an initial memory assessment between 06/04/21- 22/06/21 from the trusts electronic database.ResultsInitial baseline data showed that 0% of initial assessments screened for RBD; at the end of PDSA one this was 100% and 75% at the end of PDSA two. This increased to 100% at the end of the last PDSA cycle. The main reason for non-completion of the screening question was use of the old proforma.4/152 patients screened positive; patients were diagnosed with Alzheimer's disease, delirium, vascular dementia and mixed Alzheimer‘s disease and vascular dementia, respectively.ConclusionThe introduction of a RBD screening question into the MATS initial assessment proforma improved screening for RBD. We think the variation in screening compliance rates was likely due to practitioners using old assessment proformas, hence sending reminders of the new proforma.A limitation of the project was that some patients did not have a bed partner, which makes identification of the disorder more difficult.Since the completion of the project, we have circulated a news bulletin through the Dementia United charity to raise awareness of our QI project nationally and also discussed the project with the Lewy Body society. Whilst our project has not yet identified a patient with LBD, we feel that introducing this screening question is a very easy and reproducible change to implement and RBD should be screened for in all memory patients.
Improving the Appropriateness of Referrals From Primary to Secondary Care Confounded by the COVID Era: Student Status and Quality of Referral Evaluation in Oxford City Team (SQUARE-OCT)
Authors: Quadros Wesley , Ahmad Mohamed , Patkee Wishwanath , Katsanouli Theodora , Hyams Katy , Watkins Nicola , Krayem Amani , Bilip Maja , Zghoul Tarek , Tarfarosh Shah , Holm-Mercer Leah , Toparlak Sureyya , Tian Adam , Masood Khadija , Quested Digby 
Published: June 2022

AimsThe Oxford City and NE Oxon Adult Mental Health Team (AMHT) is an adult mental health team receiving referrals from GPs for most cases suspected to have a mental health illness requiring secondary mental health services’ input in Oxford city. In January 2020, the team was remodelled with care coordinators working in separate functions based on the duration AMHT support was required for, i.e. an assessment team and a treatment team, but with medics covering both functions of the team. This quality improvement project examines AMHT referrals over 2020/21, hypothesising a reduction in the proportion of inappropriate referrals following the remodelling compared to a 2018/19 pre-remodelling audit.MethodsThe project covers a total of 2803 referrals the team has received from 13/01/2020 to 12/01/2021. The outcomes measured included the number of inappropriate referrals returned to the GP, referrals only requiring a single assessment, the proportion of these referrals as university students in Oxford, and the diagnostic groupings of the referrals in students vs non-students. These outcomes were measured pre- and during the COVID-19 pandemic over 2020/21.ResultsA reduction in the total number of referrals to the team was noted over 2020/21 but this was compared to an 11 month audit in 2018/2019. During the study period, 19.5% (546/2803) of referrals were deemed inappropriate compared to 21% of referrals received in 2018/2019. Of 2803 referrals, 14.7% (97/658) were inappropriate pre-COVID-19 vs 20.9% (449/2145) during the pandemic. Of the total number of referrals, 32.9% were returned to the GP following a single assessment.The top 3 diagnostic categories in ‘non-students’ were mood/affective disorders (33.7%), anxiety/stress related disorders (17.2%), and neurodevelopmental disorders (7.8% total - ADHD was 3%). A significant increase in ADHD referrals and mood disorders amongst students compared to non-students is notable with the top 3 diagnostic categories for students being mood/affective (24.7%), neurodevelopmental disorders (19.5% - ADHD 17.7%), and anxiety/stress related disorders (13.4%). Students constituted 26% of the total number of referrals.It was notable that during the pandemic there was a higher proportion of inappropriate referrals.ConclusionOur project demonstrates a reduction in the proportion of inappropriate referrals sent to the AMHT following remodelling as compared to 2018/19. Further work is necessary to elucidate the contributing factors and reduce inappropriate referrals even further. An innovation is planned to automate the logging of referral outcomes to expedite a re-audit.
The extra-embryonic area opaca plays a role in positioning the primitive streak of the early chick embryo
Authors: Lee Hyung Chul , Hastings Cato , Stern Claudio D. 
Published: June 2022

ABSTRACT
Classical studies have established that the marginal zone, a ring of extra-embryonic epiblast immediately surrounding the embryonic epiblast (area pellucida) of the chick embryo, is important in setting embryonic polarity by positioning the primitive streak, the site of gastrulation. The more external extra-embryonic region (area opaca) was thought to have only nutritive and support functions. Using experimental embryology approaches, this study reveals three separable functions for this outer region. First, juxtaposition of the area opaca directly onto the area pellucida induces a new marginal zone from the latter; this induced domain is entirely posterior in character. Second, ablation and grafting experiments using an isolated anterior half of the blastoderm and pieces of area opaca suggest that the area opaca can influence the polarity of the adjacent marginal zone. Finally, we show that the loss of the ability of such isolated anterior half-embryos to regulate (re-establish polarity spontaneously) at the early primitive streak stage can be rescued by replacing the area opaca by one from a younger stage. These results uncover new roles of chick extra-embryonic tissues in early development.
Hearing without a tympanic ear
Authors: Capshaw Grace , Christensen-Dalsgaard Jakob , Carr Catherine E. 
Published: June 2022

ABSTRACTThe ability to sense and localize sound is so advantageous for survival that it is difficult to understand the almost 100 million year gap separating the appearance of early tetrapods and the emergence of an impedance-matching tympanic middle ear – which we normally regard as a prerequisite for sensitive hearing on land – in their descendants. Recent studies of hearing in extant atympanate vertebrates have provided significant insights into the ancestral state(s) and the early evolution of the terrestrial tetrapod auditory system. These reveal a mechanism for sound pressure detection and directional hearing in ‘earless’ atympanate vertebrates that may be generalizable to all tetrapods, including the earliest terrestrial species. Here, we review the structure and function of vertebrate tympanic middle ears and highlight the multiple acquisition and loss events that characterize the complex evolutionary history of this important sensory structure. We describe extratympanic pathways for sound transmission to the inner ear and synthesize findings from recent studies to propose a general mechanism for hearing in ‘earless’ atympanate vertebrates. Finally, we integrate these studies with research on tympanate species that may also rely on extratympanic mechanisms for acoustic reception of infrasound (&lt;20 Hz) and with studies on human bone conduction mechanisms of hearing.
Online randomised trials with children: A scoping review protocol
Authors: Lepage Simone , Conway Aislinn , Goodson Noah , Wicks Paul , Devane Declan 
Published: June 2022

Introduction: This scoping review will determine how online, randomised trials with children are conducted. The objectives of the review are: (a) to determine what methods and tools have been used to create and conduct online trials with children and (b) to identify the gaps in the knowledge in this field. Over the last decade, randomised trials employing online methods have gained traction. Decentralised methods lend themselves to certain types of trials and can offer advantages over traditional trial methods, potentially increasing participant reach and diversity and decreasing research waste. However, decentralised trials that have all aspects of the trial exclusively online are not yet common, and those involving children even less so. This scoping review will describe and evaluate the methods used in these trials to understand how they may be effectively employed. Methods: Methods are informed by guidance from the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. The search strategy was developed in consultation with an information specialist for the following databases: MEDLINE, CENTRAL, CINAHL, and Embase. Grey literature searches will be completed with the consultation of experts in decentralised trials and digital health using internet searches and suitable trial registries. Once identified, included full-text studies’ references will be manually searched for any trials that may have been missed. We will include randomised and quasi-randomised trials conducted exclusively online with participants under the age of 18 published in English. We will not limit by country of conduct or date of publication. Data will be collected using a data charting tool and presented in text, graphical, and tabular formats. Ethics and Dissemination: Ethical approval is not needed since all data sources used are publicly available. The review will be available as a preprint before publication in an open-access, peer-reviewed journal.