Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

BACKGROUND: Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death. AIMS: To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention. METHOD: We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care). RESULTS: We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve. CONCLUSIONS: It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.

The epidemiology and clinical features of personality disorders in later life; a study of secondary care data.

OBJECTIVES: Personality disorders (PDs) are often conceptualised as impacting individuals throughout their life. However, there has been limited study of the disorders in those over the age of 65. We have used the psychiatric secondary care medical records of 21,971 individuals over the age of 65 from Cambridgeshire, UK, who received care between 2014 and 2021 to characterise older patients with a PD diagnosis. METHODS: The data from all patients >65 with a diagnosis of personality disorder (PD) was extracted (n = 217) along with two comparison groups (n = 2170); patients <65 with a diagnosis of PD and patients >65 with a psychiatric diagnosis other than PD or dementia. RESULTS: Compared to younger patients with PD, older patients were more likely to be male, married, suffering from a mixed PD and live in less deprived areas. Compared to patients >65 with diagnoses other than PD, older patients were more likely to be female, single or divorced and had a higher level of social deprivation. Our most striking finding was that older patients with PDs were more likely to experience polypharmacy. A mean of 18.48 different drugs had been prescribed over their lifetime, compared to 9.51 for patients >65 with other mental health diagnoses. CONCLUSION: Here we present the largest ever description of this group of patients and provide insights that could inform clinical practice and future research.

Trazodone and patient outcomes in dementia-Limitations of naturalistic cohort data.

The unfolded protein response has been increasingly implicated as an important pathological pathway and target for therapeutic intervention in neurodegeneration. The licensed antidepressant trazodone is one drug which has been proposed to act on this pathway and may therefore be a potential therapy. Previous examination of existing data for patients with dementia prescribed trazodone did not find a signal suggesting a disease modifying effect. Here we add to that literature by examining the electronic patient record of patients with dementia in Cambridgeshire UK. We found that trazodone is rarely prescribed and where it is used it is at a dose less than half that predicted to be disease modifying. We also found that patients prescribed trazodone had higher levels of neuropsychiatric symptoms and were relatively late in the disease course, likely beyond the optimal point for therapeutic intervention. We suggest it is therefore premature to discard potential therapies based on observational data alone, particularly when experimental medicine approaches to examine the effects of trazodone are feasible.

Targeting the Unfolded Protein Response as a Disease-Modifying Pathway in Dementia.

Dementia is a global medical and societal challenge; it has devastating personal, social and economic costs, which will increase rapidly as the world's population ages. Despite this, there are no disease-modifying treatments for dementia; current therapy modestly improves symptoms but does not change the outcome. Therefore, new treatments are urgently needed-particularly any that can slow down the disease's progression. Many of the neurodegenerative diseases that lead to dementia are characterised by common pathological responses to abnormal protein production and misfolding in brain cells, raising the possibility of the broad application of therapeutics that target these common processes. The unfolded protein response (UPR) is one such mechanism. The UPR is a highly conserved cellular stress response to abnormal protein folding and is widely dysregulated in neurodegenerative diseases. In this review, we describe the basic machinery of the UPR, as well as the evidence for its overactivation and pathogenicity in dementia, and for the marked neuroprotective effects of its therapeutic manipulation in murine models of these disorders. We discuss drugs identified as potential UPR-modifying therapeutic agents-in particular the licensed antidepressant trazodone-and we review epidemiological and trial data from their use in human populations. Finally, we explore future directions for investigating the potential benefit of using trazodone or similar UPR-modulating compounds for disease modification in patients with dementia.

Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom.

The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.

Case report: delayed response after electroconvulsive therapy in a patient with major depressive disorder.

BACKGROUND: Major depressive disorder and associated mood syndromes are amongst the most common psychiatric disorders. To date, electroconvulsive therapy (ECT) is considered the most effective short-term treatment for patients with severe or treatment-resistant depression. In clinical practice, there is considerable variation in the ECT dosing schedule, with the number of sessions typically ranging from 6 to 12, with early antidepressant effects being predictive of increased positive outcomes. We describe here an unusual case of a female patient with severe depression who did not respond to ECT until the 11th session, after which she had shown a drastic improvement in her mental state. CASE PRESENTATION: A 75-year-old female presented to the old age psychiatry inpatient unit with new onset dysphoric mood, anhedonia, and severe negativity. She scored 23 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and was rated 6 on Clinical Global Impression severity (CGIS) by the responsible clinician. She suffered from post-natal depression fifty years ago and was successfully treated with ECT. She was therefore initiated on a course of ECT treatment. Her condition initially deteriorated, displaying features of catatonia and psychosis, unresponsive to ECT treatment or concurrent psychotropic medications. After 11th ECT session, she started to show signs of clinical improvement and returned close to her baseline mental state after a total of 17 ECT sessions. She remained well 3 months post-treatment, scoring 4 on HAM-D, Clinical Global Improvement or change (CGI-C) rated as 1 (very much improved). The diagnosis was ICD-10 F32.3 severe depressive episode with psychotic symptoms. CONCLUSIONS: we describe here an unusual case of delayed response to electroconvulsive therapy in the treatment of severe depressive disorder. Studies have shown the number of acute ECT treatments to be highly variable, affected by a number of factors including treatment frequency, condition treated and its severity, the ECT technical parameters, as well as concurrent use of pharmacological treatment. This may call for re-consideration of the current ECT treatment guidelines, requiring more research to help stratify and standardize the treatment regime.

The Nomenclature of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is an established but stigmatized psychiatric treatment. The term ECT reflects the treatment's modality and action. Several authors proposed different names for ECT to deal with stigma; however, available literature that promoted different names did not address the risk/benefit ratio or offer evidence-based approach to the efficacy of this approach. We aim to examine proposed names for their specificity, accuracy, understandability, and popularity. In addition, we aim to find evidence-based methods to combat the ECT-related stigma. We reviewed the literature relating to the proposed names using snowballing technique for literature search. Known ECT alternative names were used for search, and whenever another name appears, it was added to our search list. We conducted Medline, PsycINFO, Google Scholar, and PubMed search to check for popularity and cross examine whether proposed terms refer back to ECT. We searched for ECT and stigma, to find evidence for methods to tackle ECT-related stigma. Once, the search stopped yielding newer ideas, we stopped the search at a point of saturation, where no more ideas where generated. Our name search yielded 14 terms. Nine names avoided "electricity" and "convulsion," because of perceived associated stigma. Presence of different terminology can affect the clarity of patient-doctor communication, with no evidence of added benefit. Alternative names may affect doctor-doctor communication about this treatment. We concluded that it is safer to retain the term ECT for the sake of consistency and clarity of communication. Education and experience are evidence-based effective methods of tackling ECT-related stigma.

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

BACKGROUND: Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. METHODS: Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. RESULTS: Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. LIMITATIONS: Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. CONCLUSIONS: This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings.

Patients' Perspectives on Stigma of Mental Illness (an Egyptian Study in a Private Hospital).

The present study is concerned with the stigma of mental illness. It examines the subjective element of the experience of stigma among a sample of in-patients with different mental disorders. The sample was taken from consecutive admissions of in-patients meeting International Classification of Diseases, 10th revision (ICD-10) criteria for mental disorders who had capacity to decide on participation in the study and were willing to respond to the structured interview. The study was undertaken in an Egyptian private psychiatric hospital. The structured clinical interview included aspects of the emotional, behavioral, and cognitive effects of having a psychiatric diagnosis on in-patients with various diagnostic labels in an Egyptian psychiatric hospital. It also studied whether this effect changes with specific disorders, total duration of illness, or sociodemographic variables as gender, age, or educational level. The study illustrated the core items of stigmatization attached to the diagnosis of mental illness (1), which more than half of the participants responded affirmatively. The study aimed to explore the most prevailing aspects of stigma or social disadvantage; hoping that this may offer a preliminary guide for clinicians to address these issues in their practice.