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With the increasing application of Natural Language Processing (NLP) in Medicine at large, medical educators are urged to gain an understanding and implement NLP techniques within their own education programs to improve the workflow and make significant and rapid improvements in their programs. This paper aims to provide twelve essential tips inclusive of both conceptual and technical factors to facilitate the successful integration of NLP in medical education program evaluation. These twelve tips range from advising on various stages of planning the evaluation process, considerations for data collection, and reflections on preprocessing of data in preparation for analysis and interpretation of results. Using these twelve tips as a framework, medical researchers, educators, and administrators will have an understanding and reference to navigating applications of NLP and be able to unlock its potential for enhancing the evaluation of their own medical education programs.
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Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
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BACKGROUND: Recovery Colleges (RCs) are education-based centres providing information, networking, and skills development for managing mental health, well-being, and daily living. A central principle is co-creation involving people with lived experience of mental health/illness and/or addictions (MHA). Identified gaps are RCs evaluations and information about whether such evaluations are co-created. AIMS: We describe a co-created scoping review of how RCs are evaluated in the published and grey literature. Also assessed were: the frameworks, designs, and analyses used; the themes/outcomes reported; the trustworthiness of the evidence; and whether the evaluations are co-created. METHODS: We followed Arksey and O'Malley's methodology with one important modification: "Consultation" was re-conceptualised as "co-creator engagement" and was the first, foundational step rather than the last, optional one. RESULTS: Seventy-nine percent of the 43 included evaluations were peer-reviewed, 21% grey literature. These evaluations represented 33 RCs located in the UK (58%), Australia (15%), Canada (9%), Ireland (9%), the USA (6%), and Italy (3%). CONCLUSION: Our findings depict a developing field that is exploring a mix of evaluative approaches. However, few evaluations appeared to be co-created. Although most studies referenced co-design/co-production, few described how much or how meaningfully people with lived experience were involved in the evaluation.
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Transtornos Mentais , Humanos , Transtornos Mentais/terapia , Saúde Mental , Austrália , Canadá , ItáliaRESUMO
INTRODUCTION: Recovery colleges (RCs) are mental health centres aimed at equipping people with skills to live a meaningful life despite the presence of mental distress. Unique to them is the aspect of cocreation; RCs are designed collaboratively with people of lived experiences of mental health and addictions and care providers. Despite established benefits, there remains a lack of empirical evidence on how RCs work and on their impact. AIMS: We aim to address this gap by designing a cocreated evaluation framework for RCs. This will be accomplished by engaging RC student/facilitators to provide perspectives on RCs/RC evaluation and cocreate a scoping review identifying evaluation gaps in the literature. Themes identified through these processes will form the evaluation framework. METHODS AND ANALYSIS: Two methodologies will be used to explore RC evaluation: student/facilitator engagement and a scoping review of current published and grey literature on RC evaluation. Engagement will be achieved using a participatory action research approach consisting of informant interviews of ~25 RC students/facilitators across Canada, which will be thematically analysed. The scoping review will follow methodology described by Arksey and O'Malley modified to support cocreation. Concurrent conducting of the engagement process and scoping review will allow RC students and peer facilitators the opportunity to shape RC evaluations, address gaps in the literature and codesign an evaluation framework focused on recovery-oriented processes and outcomes mattering most to RCs students/facilitators. ETHICS AND DISSEMINATION: Ethics approval was received for the RC student/facilitator engagement component from the Centre for Addictions and Mental Health Research Ethics Board (#042-2020) and Ontario Shores Centre for Mental Health Sciences (#20-013-B). Scoping review results will be copresented through national and international medical education conferences and published in open-access peer-reviewed journals. Furthermore, a dissemination strategy on evaluation for the national RC community will be created.
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Transtornos Mentais , Participação dos Interessados , Humanos , Transtornos Mentais/terapia , Saúde Mental , Ontário , Projetos de Pesquisa , Literatura de Revisão como AssuntoRESUMO
Patients with schizophrenia have exceedingly high rates of metabolic comorbidity including type 2 diabetes and lose 15-20 years of life due to cardiovascular diseases, with early accrual of cardiometabolic disease. In this study, thirty overweight or obese (Body Mass Index (BMI) > 25) participants under 40 years old with schizophrenia spectrum disorders and early comorbid prediabetes or type 2 diabetes receiving antipsychotic medications were randomized, in a double-blind fashion, to metformin 1500 mg/day or placebo (2:1 ratio; n = 21 metformin and n = 9 placebo) for 4 months. The primary outcome measures were improvements in glucose homeostasis (HbA1c, fasting glucose) and insulin resistance (Matsuda index-derived from oral glucose tolerance tests and homeostatic model of insulin resistance (HOMA-IR)). Secondary outcome measures included changes in weight, MRI measures of fat mass and distribution, symptom severity, cognition, and hippocampal volume. Twenty-two patients (n = 14 metformin; n = 8 placebo) completed the trial. The metformin group had a significant decrease over time in the HOMA-IR (p = 0.043) and fasting blood glucose (p = 0.007) vs. placebo. There were no differences between treatment groups in the Matsuda index, HbA1c, which could suggest liver-specific effects of metformin. There were no between group differences in other secondary outcome measures, while weight loss in the metformin arm correlated significantly with decreases in subcutaneous, but not visceral or hepatic adipose tissue. Our results show that metformin improved dysglycemia and insulin sensitivity, independent of weight loss, in a young population with prediabetes/diabetes and psychosis spectrum illness, that is at extremely high risk of early cardiovascular mortality. Trial Registration: This protocol was registered with clinicaltrials.gov (NCT02167620).
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Metformina , Esquizofrenia , Adulto , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Método Duplo-Cego , Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Esquizofrenia/tratamento farmacológicoRESUMO
Introduction: Antipsychotic-induced dyslipidemia represents a common adverse effect faced by patients with schizophrenia that increases risk for developing further metabolic complications and cardiovascular disease. Despite its burden, antipsychotic-induced dyslipidemia is often left untreated, and the effectiveness of pharmacological interventions for mitigating dyslipidemia has not been well-addressed. This review aims to assess the effectiveness of pharmacological interventions in alleviating dyslipidemia in patients with schizophrenia. Methods: Medline, PsychInfo, and EMBASE were searched for all relevant English articles from 1950 to November 2020. Randomized placebo-controlled trials were included. Differences in changes in triglycerides, HDL cholesterol, LDL cholesterol, and VLDL cholesterol levels between treatment and placebo groups were meta-analyzed as primary outcomes. Results: Our review identified 48 randomized controlled trials that comprised a total of 3,128 patients and investigated 29 pharmacological interventions. Overall, pharmacological interventions were effective in lowering LDL cholesterol, triglycerides, and total cholesterol levels while increasing the levels of HDL cholesterol. Within the intervention subgroups, approved lipid-lowering agents did not reduce lipid parameters other than total cholesterol level, while antipsychotic switching and antipsychotic add-on interventions improved multiple lipid parameters, including triglycerides, LDL cholesterol, HDL cholesterol, and total cholesterol. Off label lipid lowering agents improved triglycerides and total cholesterol levels, with statistically significant changes seen with metformin. Conclusion: Currently available lipid lowering agents may not work as well in patients with schizophrenia who are being treated with antipsychotics. Additionally, antipsychotic switching, antipsychotic add-ons, and certain off label interventions might be more effective in improving some but not all associated lipid parameters. Future studies should explore novel interventions for effectively managing antipsychotic-induced dyslipidemia. Registration: PROSPERO 2020 CRD42020219982; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219982.
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Clozapine (CLZ), the sole antipsychotic with superior efficacy for ultra-treatment resistant schizophrenia (TRS), is limited by adverse effects, including metabolic dysregulation. Clozapine's main metabolite, N-desmethylclozapine (NDMC), has potent 5-HT2C antagonist properties which may explain this metabolic dysfunction, thus the CLZ:NDMC ratio is of particular interest. High insulin resistance states could be associated with CYP1A2 induction and lower CLZ:NDMC ratios. Additionally, lower CLZ:NDMC ratios have been associated with better cognitive, but worse metabolic functioning. This study investigated associations between metabolic and cognitive parameters with the CLZ/NDMC ratio. Primary outcomes included relationships between the CLZ:NDMC ratio to the homeostatic model assessment for insulin resistance (HOMA-IR) and Brief Assessment of Cognition in Schizophrenia (BACS) composite z-scores. Secondary outcomes assessed relationships between CLZ:NDMC ratios to fasting insulin, BMI, weight, fasting glucose, and BACS digit sequencing z-scores. 38 patients who were overweight or obese with schizophrenia or schizoaffective disorder completed fasting bloodwork, anthropometric, psychopathological, and cognitive assessments. Multivariate regressions found a statistically significant inverse association between the CLZ/NDMC ratio and HOMA-IR (B = - 1.028, SE B = .473, ß = - 0.348 p = 0.037), which may have been driven by fasting insulin levels (B = - 27.124, SE B = 12.081, ß = - 0.351 p = 0.031). The CLZ/NDMC ratio may predict insulin resistance/metabolic comorbidity among patients with TRS receiving clozapine.
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Obesidade Mórbida/tratamento farmacológico , Obesidade/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Clozapina/análogos & derivados , Clozapina/sangue , Cognição/fisiologia , Feminino , Humanos , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/complicações , Transtornos Psicóticos/patologia , Esquizofrenia/complicações , Esquizofrenia/patologia , Adulto JovemRESUMO
Introduction: Clozapine remains the most effective antipsychotic for treatment-refractory schizophrenia. However, ~40% of the patients respond insufficiently to clozapine. Clozapine's effects, both beneficial and adverse, have been proposed to be partially attributable to its main metabolite, N-desmethylclozapine (NDMC). However, the relation of the clozapine to norclozapine ratio (CLZ:NDMC; optimally defined as ~2) to clinical response and metabolic outcomes is not clear.Areas covered: This narrative review comprehensively examines the clinical utility of the CLZ:NDMC ratio to reduce metabolic risk and increase treatment efficacy. The association of the CLZ:NDMC ratio with changes in psychopathology, cognitive functioning, and cardiometabolic burden will be explored, as well as adjunctive treatments and their effects.Expert opinion: The literature suggests a positive association between the CLZ:NDMC ratio and better cardiometabolic outcomes. Conversely, the CLZ:NDMC ratio appears inversely associated with better cognitive functioning but less consistently with other psychiatric domains. The CLZ:NDMC ratio may be useful for predicting and monitoring cardiometabolic adverse effects and optimizing potential cognitive benefits of clozapine. Future studies are required to replicate these findings, which if substantiated, would encourage examination of adjunctive treatments aiming to alter the CLZ:NDMC ratio to best meet the needs of the individual patient, thereby broadening clozapine's clinical utility.
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Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Clozapina/efeitos adversos , Clozapina/análogos & derivados , Clozapina/sangue , Clozapina/farmacocinética , Cognição/efeitos dos fármacos , Monitoramento de Medicamentos/métodos , HumanosRESUMO
Insulin signaling in the central nervous system is at the intersection of brain and body interactions, and represents a fundamental link between metabolic and cognitive disorders. Abnormalities in brain insulin action could underlie the development of comorbid schizophrenia and type 2 diabetes. Among its functions, central nervous system insulin is involved in regulation of striatal dopamine levels, peripheral glucose homeostasis, and feeding regulation. In this review, we discuss the role and importance of central nervous system insulin in schizophrenia and diabetes pathogenesis from a historical and mechanistic perspective. We describe central nervous system insulin sites and pathways of action, with special emphasis on glucose metabolism, cognitive functioning, inflammation, and food preferences. Finally, we suggest possible mechanisms that may explain the actions of central nervous system insulin in relation to schizophrenia and diabetes, focusing on glutamate and dopamine signaling, intracellular signal transduction pathways, and brain energetics. Understanding the interplay between central nervous system insulin and schizophrenia is essential to disentangling this comorbid relationship and may provide novel treatment approaches for both neuropsychiatric and metabolic dysfunction. This article is part of the issue entitled 'Special Issue on Antipsychotics'.
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Encéfalo/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Insulina/fisiologia , Esquizofrenia/fisiopatologia , Animais , Encéfalo/metabolismo , Sistema Nervoso Central/metabolismo , Transtornos Cognitivos/fisiopatologia , Dopamina/metabolismo , Metabolismo Energético , Glucose/metabolismo , Homeostase , Humanos , Insulina/metabolismo , Obesidade/metabolismo , Receptor de Insulina/metabolismo , Esquizofrenia/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Insulin action in the central nervous system is a major regulator of energy balance and cognitive processes. The development of central insulin resistance is associated with alterations in dopaminergic reward systems and homeostatic signals affecting food intake, glucose metabolism, body weight and cognitive performance. Emerging evidence has highlighted a role for antipsychotics (APs) to modulate central insulin-mediated pathways. Although APs remain the cornerstone treatment for schizophrenia they are associated with severe metabolic complications and fail to address premorbid cognitive deficits, which characterize the disorder of schizophrenia. In this review, we first explore how the hypothesized association between schizophrenia and CNS insulin dysregulation aligns with the use of APs. We then investigate the proposed relationship between CNS insulin action and AP-mediated effects on metabolic homeostasis, and different domains of psychopathology, including cognition. We briefly discuss a potential role of CNS insulin signaling to explain the hypothesized, but somewhat controversial association between therapeutic efficacy and metabolic side effects of APs. Finally, we propose how this knowledge might inform novel treatment strategies to target difficult to treat domains of schizophrenia. This article is part of the issue entitled 'Special Issue on Antipsychotics'.
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Antipsicóticos/uso terapêutico , Encéfalo/imunologia , Resistência à Insulina/fisiologia , Insulina/imunologia , Esquizofrenia/tratamento farmacológico , Animais , Antipsicóticos/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Glucose/imunologia , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Humanos , Esquizofrenia/imunologia , Esquizofrenia/metabolismoRESUMO
OBJECTIVE: Bariatric surgery is an empirically supported treatment for severe obesity; however, it does not directly target underlying behavioural and psychological factors that potentially contribute to obesity. Mounting evidence supports the efficacy of cognitive behavioural therapy (CBT) for improving eating psychopathology and psychological distress among bariatric patients, and telephone-based CBT (Tele-CBT) is a novel delivery method that increases treatment accessibility. METHODS: This study aimed to identify demographic and clinical predictors of response to Tele-CBT among 79 patients who received Tele-CBT in 3 previous studies. Listwise deletion was applied, after which 58 patients were included in a multivariate linear regression adjusted for age, sex and education status, to evaluate patient rurality index (urban or nonurban), and baseline binge eating, emotional eating and depression symptoms, as predictors of tele-CBT response. RESULTS: The predictors explained 31% of the observed variance [R2=0.312, F(4,57)=3.238, p<0.01]. Patient rurality index (beta=0.341, p<0.01) was the only statistically significant predictor of Tele-CBT response. CONCLUSIONS: Given the limited psychosocial resources available in many bariatric surgery programs, the findings suggest that Tele-CBT may be particularly beneficial for patients residing in nonurban communities with limited access to other health-care services.
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Cirurgia Bariátrica/psicologia , Terapia Cognitivo-Comportamental/métodos , Telemedicina/métodos , Adulto , Bulimia/prevenção & controle , Bulimia/psicologia , Depressão/prevenção & controle , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Fatores Socioeconômicos , Telefone , Resultado do Tratamento , População UrbanaRESUMO
Antipsychotic (AP) medications are associated with an increased risk of developing metabolic side effects including weight gain, type 2 diabetes (T2D), dyslipidemia, and hypertension. In the majority of clinical studies, females on APs are noted to gain more weight, and are more likely to be diagnosed with metabolic syndrome when compared to males. However, the data is less clear when comparing sex disparities associated with other specific AP-induced metabolic risk factors. Accumulating evidence has demonstrated a role for AP-induced adipose tissue accumulation as well as whole body glucose dysregulation in male models that is independent of changes in body weight. The purpose of this narrative review is to explore the susceptibility of males and females to changes in adiposity and glucose metabolism across clinical and preclinical models of AP treatment. It is important that future research examining AP-induced metabolic side effects analyzes outcomes by sex to help clarify risk and identify the mechanisms of adverse event development to improve safe prescribing of medications.
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Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics-particularly the second generation, or "atypical" antipsychotics-can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health.