Comprehensive Geriatric Assessment for younger outpatients with severe mental illness: protocol for a feasibility study.

INTRODUCTION: Individuals with severe mental illness are at risk of becoming prematurely frail. There is a critical unmet need for an intervention that reduces the risk of frailty and minimises the associated negative outcomes in this population. This study aims to provide novel evidence on the feasibility, acceptability and preliminary effectiveness of Comprehensive Geriatric Assessment (CGA) to improve health outcomes among people with co-occurring frailty and severe mental illness. METHODS AND ANALYSIS: Twenty-five participants with frailty and severe mental illness, aged 18-64 years, will be recruited from Metro South Addiction and Mental Health Service outpatient clinics and provided with the CGA. Primary outcome measures will include the feasibility and acceptability of the CGA embedded in routine healthcare. Other variables of interest will include frailty status, quality of life, polypharmacy, and a range of mental and physical health factors. ETHICS AND DISSEMINATION: All procedures involving human subjects/patients were approved by Metro South Human Research Ethics Committee (HREC/2022/QMS/82272). Study findings will be disseminated through peer-reviewed publications and conference presentations.

Frailty and Treatment-Resistant Schizophrenia: A Retrospective Cohort Study.

Frailty, a state of reduced physiological reserve, has not been studied in consumers with treatment-resistant schizophrenia, despite known elevated rates of comorbidity and psychosocial impairment. This study applies a frailty index to the electronic medical records of 78 adults with treatment-resistant schizophrenia, aged 18-64 years, to determine the prevalence and characteristics of frailty (defined as a frailty index score > 0.21). The mean frailty index score was 0.24 (SD = 0.091, range = 0.061-0.54), with 52.6% of the population categorised as frail (40.0% in those aged 18-39 years). Frailty was positively correlated with age and psychiatric illness severity. This study provides novel evidence that individuals with treatment-resistant schizophrenia have a high rate of frailty and become frail at a younger age. Routine frailty assessments could be used to trigger the delivery of appropriate interventions, which have the potential to improve life expectancy and quality of life.

Frailty and solid-organ transplant candidates: a scoping review.

BACKGROUND: There is currently no consensus as to a standardized tool for frailty measurement in any patient population. In the solid-organ transplantation population, routinely identifying and quantifying frailty in potential transplant candidates would support patients and the multidisciplinary team to make well-informed, individualized, management decisions. The aim of this scoping review was to synthesise the literature regarding frailty measurement in solid-organ transplant (SOT) candidates. METHODS: A search of four databases (Cochrane, Pubmed, EMBASE and CINAHL) yielded 3124 studies. 101 studies (including heart, kidney, liver, and lung transplant candidate populations) met the inclusion criteria. RESULTS: We found that studies used a wide range of frailty tools (N = 22), including four 'established' frailty tools. The most commonly used tools were the Fried Frailty Phenotype and the Liver Frailty Index. Frailty prevalence estimates for this middle-aged, predominantly male, population varied between 2.7% and 100%. In the SOT candidate population, frailty was found to be associated with a range of adverse outcomes, with most evidence for increased mortality (including post-transplant and wait-list mortality), post-operative complications and prolonged hospitalisation. There is currently insufficient data to compare the predictive validity of frailty tools in the SOT population. CONCLUSION: Overall, there is great variability in the approach to frailty measurement in this population. Preferably, a validated frailty measurement tool would be incorporated into SOT eligibility assessments internationally with a view to facilitating comparisons between patient sub-groups and national and international transplant services with the ultimate goal of improved patient care.

A systematic review of frailty education programs for health care professionals.

OBJECTIVES: To identify and examine the reported effectiveness of education programs for health professionals on frailty. METHODS: A systematic review was conducted of articles published up to June 2021, examining the evaluation of frailty training or education programs targeting health professionals/students. The participant demographics, program content and structure, effectiveness assessment methodology and outcomes, as well as participant feedback, were recorded with narrative synthesis of results. RESULTS: There were nine programs that have evaluated training of health professionals in frailty. These programs varied with respect to intensity, duration, and delivery modality, and targeted a range of health professionals and students. The programs were well-received and found to be effective in increasing frailty knowledge and self-perceived competence in frailty assessment. Common features of successful programs included having multidisciplinary participants, delivering a clinically tailored program and using flexible teaching modalities. Of note, many programs assessed self-perceived efficacy rather than objective changes in patient outcomes. CONCLUSIONS: Despite increasing attention on frailty in clinical practice, this systematic review found that there continues to be limited reporting of frailty training programs.

Tardive Seizures After Electroconvulsive Therapy.

OBJECTIVES: Seizures that occur spontaneously after termination of an electroconvulsive therapy (ECT) seizure are termed tardive seizures. They are thought to be a rare complication of ECT, influenced by risk factors that affect seizure threshold. However, there has been limited review of tardive seizures with modified ECT. We aimed to review the literature to provide clinical guidance for the use of ECT after tardive seizures. METHODS: PubMed, EMBASE, PsycInfo, and CINAHL databases were searched from inception to May 2021 to identify cases of modified ECT, with evidence of a seizure occurring within 7 days of a terminated ECT seizure. Data for demographic, medical, pharmacological, anesthetic, and ECT variables as well as management strategies were collected. RESULTS: There have been 39 episodes of modified ECT-related tardive seizures published over a period of 40 years. In 97.4% of cases, there was at least 1 identified potential risk factor for seizures, including use of a seizure-lowering medication and/or preexisting neurological injury. Major complications were uncommon (<15% of cases); however, 1 fetal death and 1 subsequent suicide were reported. No case was diagnosed with epilepsy, although around 20% continued on antiepileptic medications. More than half of the included patients were retrialed on ECT, with only 15% developing further tardive seizures. CONCLUSIONS: Seizures that occurred spontaneously after the termination of an ECT seizure are a rare complication of modified ECT. Recommencing ECT after a tardive seizure may occur after review of modifiable seizure risk factors and with consideration of antiepileptic medication and extended post-ECT monitoring.

Frailty and severe mental illness: A systematic review and narrative synthesis.

OBJECTIVE: Emerging evidence suggests that people with severe mental illness (SMI) have an increased risk of frailty. We conducted a systematic review to investigate the prevalence and correlates of frailty, as well as the efficacy of frailty interventions, in this population. METHODS: We searched databases from inception to 21 September 2021 for studies that assessed or intervened for frailty in relation to an SMI diagnosis. A narrative synthesis explored the characteristics and adverse health outcomes associated with frailty and the efficacy of interventions. The prevalence of frailty was investigated, and its relationship with age was analysed by a meta-regression. RESULTS: Twenty-five studies involving 2499 patients, primarily older adults, were included in the narrative synthesis. Frailty was associated with higher rates of physical comorbidity, cognitive deficits, falls and mortality among those with SMI. The efficacy of a yoga intervention was investigated in one study, without sustained reductions in frailty. The prevalence of frailty varied between 10.2 and 89.7% and was high in comparison to the general population. CONCLUSIONS: The prevalence of frailty was high in those with SMI and ranged widely due to heterogeneity of study populations. Assessing frailty enables the identification of patients who could benefit from interventions and assists in treatment-related decision making. Further research is required to develop appropriate frailty interventions for this population.

The lethal heat dose for 50% primary human fibroblast cell death is 48 °C.

Understanding the effect of heat on skin cells is important for the prevention of burn injury. Knowledge of the heat dose required to kill cells can be used to study the cellular mechanisms involved in thermal injury cell death, to assist with the development of novel burn treatments. In this study, primary human skin dermal fibroblasts were exposed to temperatures from 37 to 54 °C for 1 h and the relative cell viability of heat-treated and control cells was assessed. Cell damage and viability were assessed by light microscopy, MTT assay and live/dead staining. The LD50 for 1 h of heat exposure was 48 °C for primary fibroblasts; and there was evidence that thermal damage to cells begins to occur at 43 °C. This study presents a reproducible method for examining the effect of heat on primary human cells grown in culture on a cellular level and can be used in the future to study the mechanisms behind heat-induced cell death, to inform burn injury prevention efforts and effective post-burn treatment.

Clozapine levels as a predictor for therapeutic response: A systematic review and meta-analysis.

OBJECTIVES: Clozapine levels may be a more useful predictor of therapeutic response than the dose, given the variability in clozapine metabolism between individuals. We therefore systematically reviewed and meta-analysed the impact of clozapine levels on response and/or relapse to provide guidance on optimal clozapine levels. METHODS: We systematically searched PubMed, PsycInfo and Embase for studies exploring clozapine levels and response and/or relapse. Our primary meta-analysis was rates of response above and below clozapine level thresholds of 350 ng/ml and 600 ng/ml. Secondary analyses were undertaken of mean clozapine levels, dose and concentration/dose (C/D) ratio and response and/or relapse. A meta-regression by study duration was conducted. RESULTS: Twenty studies met inclusion criteria. Clozapine levels above 350 ng/ml were associated with statistically significantly higher rates of response (OR 2.27 95% CI 1.40-3.67, p < 0.001), but not above 600 ng/ml (OR 1.40 95% CI 0.85-2.31, p = 0.19). Higher mean clozapine levels were associated with better rates of response (SMD 0.24, 95% CI 0.00-0.49, p = 0.05), and lower rates of relapse (SMD -0.72, 95% CI -1.26 to -0.19, p = 0.008). By contrast, neither clozapine dose nor C/D ratio was associated with differing rates of response. Similarly, study duration did not affect outcome. CONCLUSIONS: Our findings are in keeping with current guidelines that recommend targeting clozapine levels above 350 ng/ml before augmentation is considered. As some clozapine associated ADRs are dose dependent, levels above 600 ng/ml may have an unfavourable risk-benefit ratio.