Observational cohort study of the triggers, diagnoses and outcomes of the medical emergency team (MET) response in adult psychiatry inpatients colocated with acute medical services in Australia

ObjectivesMedical emergencies in psychiatric inpatients are challenging due to the model of care and limited medical resources. The study aims were to determine the triggers and outcomes of a medical emergency team (MET) call in psychiatric wards, and the risk factors for MET activation and mortality.DesignRetrospective multisite cohort study.SettingPsychiatry units colocated with acute medical services at three major metropolitan hospitals in Melbourne, Australia.ParticipantsWe studied 487 adult inpatients who experienced a total of 721 MET calls between January 2015 and January 2020. Patients were relatively young (mean age, 45 years) and had few medical comorbidities, but a high prevalence of smoking, excessive alcohol intake and illicit drug use.Outcome measuresWe performed a descriptive analysis of the triggers and outcomes (transfer rates, investigations, final diagnosis) of MET calls. We used logistic regression to determine the factors associated with the primary outcome of inpatient mortality, and the secondary outcome of the need for specific medical treatment compared with simple observation.ResultsThe most common MET triggers were a reduced Glasgow Coma Scale, tachycardia and hypotension, and 49% of patients required transfer. The most frequent diagnosis was a drug adverse effect or toxidrome, followed by infection and dehydration. There was a strong association between a leave of absence and MET calls, tachycardia and the final diagnosis of drug adverse effects. Mortality occurred in 3% after MET calls. Several baseline and MET clinical variables were associated with mortality but a model with age (per 10 years, OR 1.61, 95% CI 1.29 to 2.01) and hypoxia (OR 3.59, 95% CI 1.43 to 9.04) independently predicted mortality.ConclusionVigilance is required in patients returning from day leave, and drug adverse effects remain a challenging problem in psychiatric units. Hypoxic older patients with cardiovascular comorbidity have a higher risk of death.

Partial regression of foveoschisis following vitamin B6 supplementary therapy for gyrate atrophy in a Chinese girl

Background To report a case of genetically confirmed gyrate atrophy (GA) of choroid and retina, who showed partial regression of foveoschisis following vitamin B6 supplementary therapy. Case presentation A 6-year-old Chinese girl complained about night blindness and progressive decreased vision in both eyes. Her best corrected visual acuity (BCVA) was 20/63 OD and 20/100 OS. Fundus examination showed bilateral multiple, sharply demarcated, scallop-shaped chorioretinal atrophy areas in the midperipheral and peripheral of the fundus. Spectral domain optical coherence tomography (SD-OCT) showed increased central macular thickness (CMT) with multiple intraretinal cystic spaces in the both eyes. There was no leakage or staining in the macular area in late phase of fluorescein angiography (FA). Blood tests confirmed hyperornithinemia and genetic analysis revealed two heterozygous mutations on ornithine aminotransferase (OAT) gene. Based on clinical presentation and genetic test, the patient was diagnosed as GA of the choroid and retina and further treated with vitamin B6 supplementary for three weeks. Her serum ornithine levels did not change but CMT on SD-OCT declined with partial regression of intraretinal cystic spaces. Then, the patient discontinued the drug because of severe muscle pain, and foveoschisis increased to initial level a month later. Conclusions Foveoschisis is a rare complication of GA. Vitamin B6 supplementation may alleviate foveoschisis, but its effort for reducing serum ornithine level might be limited. Potential drug adverse effects should be noted in pediatric patients.

Cannabidiol Use as Treatment for Refractory Epilepsies

Introduction: Refractory epilepsies have a great impact in patients’ quality of life. Thus, studies with alternative drugs are extremely important to seek for effective treatments to control the condition, and cannabidiol (CBD) has shown promising results. Objectives: To analyze CBD’s efficacy as an alternative treatment of patients with refractory epilepsy. Design and setting: this study is a literature review from Universidade Federal da Bahia. Methods: We searched the following formula on PubMed: [cannabidiol] AND [epilepsy]. The inclusion criteria were clinical trials published from 2016-2021. Results: 25 articles were found, from which 18 were selected and, from those, 1092 patients were analyzed. All studies pointed to a reduction in frequency and/or intensity of epileptic crisis in adults and children with refractory epilepsy using CBD, independently of the etiology. In Laux’s study, they noted reductions of 50% and 44% in motor and total seizures (respectively). Moreover, Birnbaum’s study showed that using CBD with a meal may cause variability of exposure of patients to the drug. Adverse effects were dose dependent, mainly diarrhea, sleepiness and less appetite. The interaction between CBD and anticonvulsants was not shown to have a prejudicial or neutralizing effect. Conclusion: CBD was shown to be capable of attenuating attacks in patients with refractory epilepsy. However, more randomized clinical trials are needed to analyze the efficacy and the safety of these medications in the short and long term.

467 - A narrative review of the deprescribing process in patients with dementia

Deprescribing, an integral component of a continuum of good prescribing practices, is the process of medication withdrawal or dose reduction to correct or prevent medication-related complications, improve outcomes, and reduce costs. Deprescribing can be a challenge in patients with dementia. In this narrative review we evaluate topics related with deprescribing: what constitutes deprescribing, the importance to deprescribing for patients with dementia, the potential benefits, barriers and enablers of deprescribing and the deprescribing process.Patients with dementia often have multiple comorbidities and have complex medication regimens. Also, they face challenges with medication adherence because of the nature of the disease. Proper medication adherence is important to prevent progression of these comorbidities and decline in overall health. However, as dementia progresses, the risk of taking certain medications may outweigh the benefits. In addition, older people, especially those with physical and mental decline, tend to experience lower efficacy of these medications along with a higher risk of drug adverse effects. As with prescribing or continuing medications, deprescribing brings with it the potential for harm as well as benefit. Other barriers to deprescription include concerns from the patients or the family, worries and doubts from the physician and some issues related to each health system. Many challenges for its execution have been described.Recent studies report benefits and safety in the prescription of patients with dementia, reinforcing the importance of considering prescription in the reevaluation of the patient. Advance care planning is the cornerstone of palliative care, and prescription should be considered in this process.

Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects

Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects. Impact statement Cardiac and hepatic adverse drug effects are among the leading causes of attrition in preclinical and clinical drug development programs as well as marketing withdrawals. The insufficiency of animal testing models has led to considerable interest in the employment of cardiac and hepatic models using human-induced pluripotent stem cells (iPSCs) for drug toxicity testing. However, current batches of iPSC-derived cardiomyocytes and hepatocytes are variable and not matured as adult primary tissues, which limit their prediction of drug effects. This article discusses how the use of microfluidics can create microenvironments to better control differentiation protocols and increase the physiological relevance of iPSC-derived cardiomyocytes and hepatocytes. Development and standardization of technologies will enable evaluation of the potential value of cellular microsystems to improve the in vitro models used in drug development programs. Future steps in this field include controlled connections of organ systems to better recreate clinical metabolism and pharmacokinetics.

Non-Tuberculous Mycobacterial Diseases in Children

Non-tuberculous mycobacteria (NTMs) are ubiquitous and opportunistic emerging bacteria with the potential to colonize and eventually infect either immunocompromised or immunocompetent individuals. In the last three decades, the prevalence of disease caused by NTMs has increased in several countries. The increased prevalence of NTM infection can be explained by an ageing population with rising comorbidities, HIV infection, the common use of immunosuppressive drugs, and improved diagnostic methods. The aim of this review is to demonstrate the clinical relevance of NTMs in children, describing their features and manifestations, diagnostic tools, and therapeutic approaches. We collected data from the literature about NTM infections in young patients over the past five years (2014–2019) using the keywords “non-tuberculous”, “mycobacteria”, “paediatric”, “NTM”, “cystic fibrosis”, and “children”. Recent literature points out that NTMs are ubiquitous, with several species including both those that are pathogens for humans and those that are not. This means that, if a mycobacterium is isolated from a patient’s specimen, we have to distinguish between a simple colonization and an NTM-related disease. The start of treatment depends on many factors that are necessary to consider, such as clinical and imaging features, patient comorbidity and immunocompetence, drug adverse effects, and compliance with a very long therapy that can last many months. Due to the increasing prevalence and clinical relevance of NTMs, guidelines for their optimal management, especially in the presence of chronic underlying disease, are urgently needed.