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.

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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.

ObjectivesSeizures 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.MethodsPubMed, 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.ResultsThere 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.ConclusionsSeizures 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.

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