bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Audit of Rapid Tranquilisation in Mental Health Services for Older People (MHSOP)
Authors: Hern Daniel , Salim Tahir , Oduma Mabel , Langford Wren 
Published: August 2024

AimsRapid Tranquilisation (RT) is the parenteral (intramuscular) administration of medication to calm or sedate an agitated, violent or aggressive patient in a timely and safe manner. This audit specifically looks at the clinical practice in the use of rapid tranquilisation in inpatient MHSOP against trust policy. The aim of this audit is to assess the effectiveness of RT and if other methods of de-escalation are being utilized first to provide better care for patients and utilize the least restrictive management options possible.MethodsThe audit was registered, and care was taken to uphold ethics, access patient information appropriately, and to ensure that data collected was both relevant and ensured confidentiality. All incidents of RT were identified across both wards of Auckland Park Hospital from the period of August to October 2023. DATIX numbers were identified to show incidents of RT from the specified period, these numbers were used to identify patient ID with liaison with relevant staff members. Patient ID was used to review the incident, specifically to investigate de-escalation techniques documented and effectiveness of RT. Only parenteral RT incidents were included to assess if appropriate measures were taken beforehand.ResultsA total of six Incident reports were identified over the three-month period. In all cases the choice and dose of the medication was within the current recommendations. 33% of incidents utilised promethazine 25mg while the other 66% utilised lorazepam either 1mg or 500mcg. All patients had baseline observations recorded on NEWS chart prior to the incident, however only 33% of incidents involved full recordings of observations at appropriate intervals on the NEWS chart. The reason for this in all cases was due to patient refusing observations which was documented. There were no documented side effects but 33% of incidents involved a raised NEWS score post RT. In all cases the NEWS score resolved spontaneously within the post RT monitoring period. In 100% of incidents de-escalation techniques were utilised and documented and evidence of post RT debrief with the patient was shown. 66% of incidents involved a medication review post RT as per recommendations.ConclusionGuidelines are being followed with good effect regarding RT in MHSOP. It is important to always undertake nonpharmacological de-escalation methods prior to considering RT which is reflected in the low numbers of RT during this period. Recommendations are made to follow local guidance as well as to exhaust nonpharmacological de-escalation methods to reduce the need for RT.
Challenges and Delay in Treatment With Clozapine Due to Thrombocytopenia: A Case Study
Authors: Thapaliya Suresh , Boutell Glenda , Firdosi Mudasir 
Published: August 2024

AimsClozapine is the most effective antipsychotic medication for patients with treatment-resistant psychotic disorders. Its discontinuation can precipitate relapse that can be often challenging to treat.MethodsThis is a case study of a female patient in her early 40s who is known to the mental health services with a diagnosis of schizoaffective disorder. She was admitted to acute psychiatric inpatient unit due to relapse characterised by psychotic, catatonic features and poor physical health condition due to refusal to eat and drink. She was stable on clozapine for more than a decade and had become unwell after discontinuation of clozapine in the community due to platelet count below 50 × 109/L with normal other parameters. Low platelet count was detected during routine monthly blood monitoring after a few years of commencing clozapine.Whilst an inpatient, there were several trials of re-titration of clozapine which had to be withheld because of ambiguity regarding the cause of persistent thrombocytopenia. Other treatment options including alternative antipsychotics and 12 sessions of ECT were tried without any success. Haematologist opinion was sought at early stage of admission and blood investigations were done but there was delay in bone marrow biopsy due to practical issues.The treating team re-commenced oral clozapine to which she remained initially non-compliant due to catatonic features. With advice from the specialist psychosis services a few doses of intramuscular clozapine was used to facilitate re-titration. Following regular compliance and optimisation of oral clozapine, there was significant remission of clinical symptoms, with patient returning to her baseline mental state and functioning. During the period of admission, platelet counts were closely monitored which kept fluctuating reaching sometimes below 30 × 109/L without any clear association with clozapine dose. No bleeding symptoms or signs were ever reported.ResultsClozapine is a medication with haematological side effects; however, low platelet count is very rare. This patient ultimately underwent bone marrow biopsy which established Immune thrombocytopenia. She was discharged to the community with a plan of continuing clozapine, close monitoring of blood count and regular follow-up with haematology services for further clinical management.ConclusionCareful clinical evaluation and timely investigation is important to establish the cause for side effects before associating it with clozapine and discontinuing the treatment. This helps in ensuring continuity of clozapine in patients who clearly benefit from long-term use of clozapine.
Systematic Literature Review and Meta-Analysis of Anti-Psychotic Use in Parkinson's Disease Psychosis
Authors: McKeown Christopher , Salmoiraghi Alberto 
Published: August 2024

AimsPsychosis is a common neuropsychiatric symptom associated with Parkinson's disease (PD), with prevalence rates of up to 75%. Parkinson's disease psychosis (PDP) is associated with increased morbidity, caregiver burden, depression, poorer quality of life and progression of dementia. It has also been shown to be a strong predictive factor for long term care placement, and results in up to 71% increase in risk of mortality compared with PD patients free from psychotic symptoms. Use of antipsychotics for PDP is common, with up to 35% of PD patients prescribed at least one antipsychotic within 7 years of PD diagnosis. This systematic literature review aims to search, appraise and synthesise the best available and most up-to-date evidence for the use of antipsychotics in the treatment of PDP, and their effects on PD motor symptoms.MethodsWe carried out a comprehensive literature review and meta-analysis following the PRISMA statement for systematic reviews.ResultsFour studies investigated quetiapine, three investigated olanzapine, two investigated clozapine and a further two investigated pimavanserin. Both quetiapine and olanzapine showed no significant improvement for PDP over placebo, however meta-analysis of olanzapine groups showed significant motor worsening, UPDRS +2.89 (95% CI 1.22 to 4.56) compared with placebo. Clozapine showed a significant improvement in psychosis vs placebo in both studies, with a large effect size in their primary outcome measure; -0.82 (95% CI -1.37 to -0.26), -0.89 (95% CI -1.42 to - 0.36). Pimavanserin showed significant improvement in psychosis vs placebo -0.48 (95% CI -0.77 to -0.18). Quetiapine, clozapine and pimavanserin showed no significant worsening in motor scores vs placebo group.ConclusionAlthough Olanzapine and Quetiapine are commonly used to treat psychotic symptoms in Parkinson's Disease, the only medication with robust evidence is Clozapine. This finding may have implications for service delivery.
Modulating N-Methyl D-Aspartate Receptors to Enhance Learning of Safety Memories in a Rodent Model of Exposure Therapy
Authors: Thursby Alice , Sherman Emily , Cahill Emma 
Published: August 2024

AimsOveractive negative memories are thought to contribute to the core symptoms of psychiatric conditions such as anxiety disorders or post-traumatic stress disorder (PTSD). For talking therapies, such as exposure therapy, there are high rates of relapse demonstrating the necessity for innovative new treatments. It is thought that enhancing the ability to extinguish fear responses to the reactivation of these memories in patients with pharmacological adjunct treatments will enhance the efficacy of interventions.N-methyl D-aspartate receptors (NMDARs) regulate the process of memory formation and consolidation. It is hypothesised that increasing the function of NMDARs would augment the consolidation of safety learning, during treatment sessions. NMDARs require the co-agonists glycine or d-serine to function. Bitopertin, a GlyT-1 inhibitor, increases the availability of glycine. Bitopertin has been studied in the context of schizophrenia, and therefore has been demonstrated to be safe for use in humans. In this preclinical study, we aim to determine if bitopertin can enhance safety learning, so-called extinction, in rodent models.Methods24 Lister Hooded rats (male, n = 12) will undergo aversive Pavlovian conditioning to form an associative memory. Rats will then be administered with saline or bitopertin systemically, prior to a session to extinguish fear responses. The strength of the extinction of responses will be measured the following day with a rapid re-acquisition test.ResultsThis study is being carried out as part of an intercalated master's degree, so the final results will be available in spring 2024. Given pilot data, it is expected that we will observe that the rats administered with bitopertin exhibit lower levels of fear responses on the rapid reacquisition test than the rats administered with saline. We do not predict any sex difference in responses. This would demonstrate bitopertin has the potential to enhance and safety memory consolidation in rats.ConclusionThis is an exciting area of research for which results could provide a break-through in improving talking therapies and adjunct treatments offered to patients with anxiety disorders. Negative results would be informative as this allows neurobiologists to refine the search for a pharmacological agent which could be used as a cognitive enhancer in this manner.
Review of Rapid Tranquillisation Guidelines Across NHS Trusts in England
Authors: Chavasse Claudia , O'Neill James , Romeu Daniel , Graham Alex 
Published: August 2024

AimsRapid tranquillisation – the parenteral administration of a sedating psychotropic – is frequently utilised to manage acute behavioural disturbances. Each mental health trust in England utilises independent guidelines for rapid tranquillisation, which vary geographically in both recommendations for therapeutic agents, as well as the format in which this information presented. Audits have identified that there is currently poor adherence to rapid tranquillisation protocol guidelines; this may be due to a lack of guideline clarity allowing for personal interpretation. This service evaluation aims to determine the clarity and uniformity of protocols outlined in mental health trust guidelines, in addition to analysing the outcomes of guideline testing to identify if there is consistency between policies, or whether outcomes varied depending on the trust guidelines used.MethodsFive reviewers (of differing positions throughout clinical training) utilised 52 guidelines from each mental health trust in England, as well as Maudsley and NICE. These were assessed using the same fictional scenario, which simulated a common presentation in which the use of rapid tranquillisation is required. Reviewers deduced the most appropriate therapeutic agent according to the guideline, rated the clarity of each guideline and were invited to leave comments highlighting the guideline's useability.ResultsSeven different management plans were generated by the majority of respondents from the 52 guidelines. Lorazepam was the most frequently selected therapeutic agent. Guidelines with better subjective ratings of clarity had more agreement between reviewers, but full agreement between reviewers was only present for 10 out of 52 guidelines. For 11 guidelines, consensual agreement between reviewers was not reached. Qualitative analysis of comments identified the inclusion of past medical history, drug history and flow charts as positive sub-themes. Redundant language, contradictions and the suggestion to seek senior intervention before trialling a second agent were viewed negatively. Many guidelines did not sufficiently emphasise the need for performing an ECG before administering therapeutic agents, such as haloperidol, which may lead to potentially fatal arrhythmias.ConclusionThere is no national consensus on the most appropriate rapid tranquillisation agents, with the available evidence being interpreted variously by different trusts and organisations. Poor guideline comprehensibility impacts clinician adherence and allows for personal preference to influence choice of drug. Clear guidelines utilising flow charts to succinctly outline relevant doses and absolute contraindications were viewed favourably by reviewers. The findings of this project highlights to relevant stakeholders the attributes that should be implemented when improving guidelines for the future.
Paraneoplastic Neurologic Disorders
Authors: Zekeridou Anastasia 
Published: August 2024

ABSTRACT

OBJECTIVE
This article reviews the clinical presentations, neural antibody associations, and oncologic accompaniments of paraneoplastic neurologic syndromes and neurologic autoimmunity in the context of immune checkpoint inhibitor (ICI) cancer immunotherapy.

LATEST DEVELOPMENTS
Neural antibody discovery has improved the diagnosis of paraneoplastic neurologic syndromes. Neural antibodies also delineate the underlying disease pathophysiology and thus inform outcomes and treatments. Neural antibodies specific for extracellular proteins have pathogenic potential, whereas antibodies specific for intracellular targets are biomarkers of a cytotoxic T-cell immune response. A recent update in paraneoplastic neurologic syndrome criteria suggests high- and intermediate-risk phenotypes as well as neural antibodies to improve diagnostic accuracy in patients with paraneoplastic neurologic syndromes; a score was created based on this categorization. The introduction of ICI cancer immunotherapy has led to an increase in cancer-related neurologic autoimmunity with distinct clinical phenotypes.

ESSENTIAL POINTS
Paraneoplastic neurologic syndromes reflect an ongoing immunologic response to cancer mediated by effector T cells or antibodies. Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis, and neural antibodies aid diagnosis, focus cancer screening, and inform prognosis and therapy. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. ICI therapy has led to immune-mediated neurologic complications. Recognition and treatment lead to improved outcomes.
The Neurologist’s Guide to Drug Pricing in the United States
Authors: Nair Kavita V. , Santoro Jonathan D. 
Published: August 2024

ABSTRACT
As newer, innovative neurology drugs enter the US health care system, neurologists should consider the cost of these treatments in addition to their efficacy, safety, and tolerability. To do so thoughtfully requires an understanding of how prescription drugs are priced in the United States. The process of drug pricing is linked to the distribution supply chain and the many stakeholders involved. Stakeholders include pharmaceutical manufacturers; wholesalers; pharmacies; pharmacy benefit managers; payers, including health insurers; hospital systems; neurologists and other clinicians; and patients. Drug pricing has taken center stage as the Inflation Reduction Act of 2022 has set maximum out-of-pocket expenses for Medicare beneficiaries for the first time in the program’s history and limits drug price increases for a select group of Medicare Part D drugs. This article describes the US drug distribution supply chain and its stakeholders and introduces key drug pricing terms; a brief description of how rebates are generally estimated will also be discussed. Finally, as newer neurology outpatient drugs enter the market, the “value” of drugs will be described through cost-effectiveness terminology and their utility for the clinical neurologist.
Therapeutic Approach to Autoimmune Neurologic Disorders
Authors: Clardy Stacey L. , Smith Tammy L. 
Published: August 2024

ABSTRACT

OBJECTIVE
Autoimmune neurologic disorders encompass a broad category of diseases characterized by immune system attack of the central, peripheral, or autonomic nervous systems. This article provides information on both acute and maintenance immunotherapy used to treat autoimmune neurologic disorders as well as a review of symptomatic management and special considerations when caring for patients with these diseases.

LATEST DEVELOPMENTS
Over the past 20 years, more than 50 antibodies have been identified and associated with autoimmune neurologic disorders. Although advances in diagnostic testing have allowed for more rapid diagnosis, the therapeutic approach to these disorders has largely continued to rely on expert opinion, case series, and case reports. With US Food and Drug Administration (FDA) approval of biologic agents to treat neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis as well as ongoing clinical trials for the treatment of autoimmune encephalitis, the landscape of immunotherapy options continues to expand. Consideration of the unique pathogenesis of individual autoimmune neurologic disorders as well as the mechanism of action of the diverse range of treatment options can help guide treatment decisions today while evidence from clinical trials informs new therapeutics in the future.

ESSENTIAL POINTS
Recognizing patients who have a clinical history and examination findings concerning for autoimmune neurologic disorders and conducting a thorough and directed imaging and laboratory evaluation aimed at ruling out mimics, identifying specific autoimmune syndromes, and screening for factors that may have an impact on immunotherapy choices early in the clinical course are essential to providing optimal care for these patients. Providers must consider immunotherapy, symptomatic treatment, and a multidisciplinary approach that addresses each patient’s unique needs when treating patients with autoimmune neurologic disorders.
Electroencephalogram-Based Anesthesia Indices Differently React to Modulations of Alpha-Oscillatory Activity
Authors: Kinateder Thomas , Kratzer Stephan , Husemann Cornelius , Hautmann Hubert , García Paul S. , Schneider Gerhard , Kreuzer Matthias 
Published: August 2024

BACKGROUND:
The electroencephalographic (EEG) provides the anesthesiologist with information regarding the level of anesthesia. Processed EEG indices are available that reflect the level of anesthesia as a single number. Strong oscillatory EEG activity in the alpha-band may be associated with an adequate level of anesthesia and a lower incidence of cognitive sequelae. So far, we do not know how the processed indices would react to changes in the alpha-band activity. Hence, we modulated the alpha-oscillatory activity of intraoperative EEG to assess possible index changes.

METHODS:
We performed our analyses based on data from 2 studies. Intraoperative EEG was extracted, and we isolated the alpha-band activity by band-pass filtering (8–12 Hz). We added or subtracted this activity to the original EEG in different steps with different amplifications of the alpha signal. We then replayed these signals to the bispectral index (BIS), the Entropy Module (state entropy [SE]), the CONOX (qCON), and the SEDLine (patient state index [PSI]); and evaluated the alpha-band modulation’s impact on the respective index.

RESULTS:
The indices behaved differently to the modulation. In general, indices decreased with stronger alpha-band activity, but the rate of change was different with SE showing the strongest change (9% per step) and PSI and BIS (<5% per step) showing the weakest change. A simple regression analysis revealed a decrease of 0.02 to 0.09 index points with increasing alpha amplification.

CONCLUSIONS:
While the alpha-band in the intraoperative EEG seems to carry information regarding the quality of anesthesia, changes in the alpha-band activity do neither strongly nor uniformly influence processed EEG indices. Hence, to assess alpha-oscillatory activity’s strength, the user needs to focus on the raw EEG or its spectral representation also displayed on the monitoring systems.
Percutaneous Achilles tendon tenotomy in clubfoot with a blade or a needle: a single-centre randomized controlled noninferiority trial
Authors: Pigeolet Manon , Ghufran Syed Jabbar , Ahmed Sadia , Chinoy Muhammad A. , Khan Mansoor A. 
Published: August 2024

AimsThe gold standard for percutaneous Achilles tendon tenotomy during the Ponseti treatment for idiopathic clubfoot is a tenotomy with a No. 15 blade. This trial aims to establish the technique where the tenotomy is performed with a large-bore needle as noninferior to the gold standard.MethodsWe randomized feet from children aged below 36 months with idiopathic clubfoot on a 1:1 basis in either the blade or needle group. Follow-up was conducted at three weeks and three months postoperatively, where dorsiflexion range, Pirani scores, and complications were recorded. The noninferiority margin was set at 4° difference in dorsiflexion range at three months postoperatively.ResultsThe blade group had more dorsiflexion at both follow-up consultations: 18.36° versus 18.03° (p = 0.115) at three weeks and 18.96° versus 18.26° (p = 0.001) at three months. The difference of the mean at three months 0.7° is well below the noninferiority margin of 4°. There was no significant difference in Pirani scores. The blade group had more extensive scar marks at three months than the needle group (8 vs 2). No major complications were recorded.ConclusionThe needle tenotomy is noninferior to the blade tenotomy for usage in Ponseti treatment for idiopathic clubfoot in children aged below 36 months.Cite this article: Bone Joint J 2024;106-B(8):871–878.
Protocol for a cluster randomized study to compare the effectiveness of a self-report distress tool and a mental health referral service to usual case management on program completion among vulnerable youth enrolled in a vocational training program
Authors: Bailey Shawna , Stoner Carrie , Cruise Kelly , DiDiodato Giulio 
Published: August 2024

Objectives
1) To compare the effect of the self-report distress tool (DT) and rapid mental health referral process (MH) on vocational training program attendance.
2) To compare the effect of the DT and MH on vocational training program completion.
3) To compare the effect of the DT an MH on post-vocational training program employment.

Design
Pragmatic, multi-centre, 2x2 factorial, cluster randomized, superiority study with 4 parallel groups and primary endpoints of vocational program attendance and completion at 12 weeks and post-program employment at 24 months. Cluster randomization of each training cohort will be performed with a 1:1:1:1 allocation ratio using a site stratified, permuted-block group schema. Final sample size is expected to be 400 participants (100 per group).

Participants
Students enrolled in Community Builder’s Trades & Diversity Training Program in either the city of Barrie or Sudbury (in Ontario, Canada) will be eligible for enrollment if they have an active Ontario Health Insurance Plan number and Canadian Social Insurance Number and provide written informed consent prior to Training program commencement.

Outcomes
The primary outcome includes:
1) Difference in proportion of absence-free program days from date of randomization, where absence-free days are defined as being present in class or work setting for ≥ 8 hours from Monday to Thursday during the 12-week program duration.

Trial registration
ClinicalTrials.gov NCT05626374 (November 23, 2022).