Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures

An organ-on-chip platform equipped with microsensors for long-term microfluidic cultivation and metabolic monitoring (O2, Glu, Lac) of 3D tumour organoid cultures grown from patient-derived single cancer stem cells.

Quality prescribing in early psychosis: key pharmacotherapy principles

Objective: To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis. Method: Identification and explanation of key principles relating to evidence-based pharmacotherapy for people with early psychosis. These were derived from the literature, practice guidelines and clinical experience. Results: Key principles include (1) medication choice informed by adverse effects; (2) metabolic monitoring at baseline and at regular intervals; (3) comprehensive and regular medication risk–benefit assessment and psychoeducation; (4) early consideration of long-acting injectable formulations (preferably driven by informed patient choice); (5) identification and treatment of comorbid mood disorders and (6) early consideration of clozapine when treatment refractory criteria are met. Conclusions: Current prescribing practices do not align with the well-established evidence for quality pharmacotherapy in early psychosis. Adopting evidence-based prescribing practices for people with early psychosis will improve outcomes.

The Therapeutic Potential and Limitations of Ketones in Traumatic Brain Injury

Traumatic brain injury (TBI) represents a significant health crisis. To date, no FDA approved pharmacotherapies are available to prevent the neurological deficits caused by TBI. As an alternative to pharmacotherapy treatment of TBI, ketones could be used as a metabolically based therapeutic strategy. Ketones can help combat post-traumatic cerebral energy deficits while also reducing inflammation, oxidative stress, and neurodegeneration. Experimental models of TBI suggest that administering ketones to TBI patients may provide significant benefits to improve recovery. However, studies evaluating the effectiveness of ketones in human TBI are limited. Unanswered questions remain about age- and sex-dependent factors, the optimal timing and duration of ketone supplementation, and the optimal levels of circulating and cerebral ketones. Further research and improvements in metabolic monitoring technology are also needed to determine if ketone supplementation can improve TBI recovery outcomes in humans.

Cellular NADH and NADPH Conformation as a Real-Time Fluorescence-Based Metabolic Indicator under Pressurized Conditions

Cellular conformation of reduced pyridine nucleotides NADH and NADPH sensed using autofluorescence spectroscopy is presented as a real-time metabolic indicator under pressurized conditions. The approach provides information on the role of pressure in energy metabolism and antioxidant defense with applications in agriculture and food technologies. Here, we use spectral phasor analysis on UV-excited autofluorescence from Saccharomyces cerevisiae (baker’s yeast) to assess the involvement of one or multiple NADH- or NADPH-linked pathways based on the presence of two-component spectral behavior during a metabolic response. To demonstrate metabolic monitoring under pressure, we first present the autofluorescence response to cyanide (a respiratory inhibitor) at 32 MPa. Although ambient and high-pressure responses remain similar, pressure itself also induces a response that is consistent with a change in cellular redox state and ROS production. Next, as an example of an autofluorescence response altered by pressurization, we investigate the response to ethanol at ambient, 12 MPa, and 30 MPa pressure. Ethanol (another respiratory inhibitor) and cyanide induce similar responses at ambient pressure. The onset of non-two-component spectral behavior upon pressurization suggests a change in the mechanism of ethanol action. Overall, results point to new avenues of investigation in piezophysiology by providing a way of visualizing metabolism and mitochondrial function under pressurized conditions.

Biomarkers of Glyco-Metabolic Control in Hemodialysis Patients: Glycated Hemoglobin vs. Glycated Albumin

Background and Objectives: Glycated hemoglobin (HbA1c) dosage is considered the gold standard in glycol-metabolic monitoring, but it presents limits, which can underestimate the glycemia trend. In this regard, it was introduced the glycated albumin (GA). The aim of the study is to verify the predictivity of the GA compared to HbA1c in identifying glyco-metabolic alterations in non-diabetic and diabetic hemodialysis (HD) patients. Materials and Methods: For this purpose, we conducted a multicenter study involving one analysis laboratory and six dialysis centers in the Lazio region (Rome, Italy). Both diabetic and non-diabetic HD patients represent the study population, and the protocol included five time points. Results: The analyzed data highlighted the ability of GA to predict changes in glycemic metabolism in HD patients, and GA values are not significantly influenced, like HbA1c, by dialysis therapy itself and by comorbidities of the uremic state, such as normochromic and normocytic anemia. Thus, GA seems to reflect early glyco-metabolic alterations, both in patients with a previous diagnosis of diabetes and in subjects without diabetes mellitus. As part of this study, we analyzed two HD patients (one diabetic and one non-diabetic) in which GA was more predictive of glycol-metabolic alterations compared to HbA1c. Our study confirms the need to compare classical biomarkers used for the monitoring of glyco-metabolic alterations with new ones, likely more reliable and effective in specific subgroups of patients in which the classic biomarkers can be influenced by the preexisting pathological conditions. Conclusions: In conclusion, our evidence highlights that in uremic patients, GA shows a better ability to predict glyco-metabolic alterations allowing both an earlier diagnosis of DM and a prompt modulation of the hypoglycemic therapy, thus improving the clinical management of these patients.

Management algorithms and artificial intelligence systems for cardiopulmonary bypass

This article introduces management algorithms to support operators in choosing the best strategy for metabolic management during cardiopulmonary bypass using artificial intelligence systems. We developed algorithms for the identification of the optimal way for assessing metabolic parameters. Different management algorithms for extracorporeal procedures interfaced with metabolic monitoring systems already exist on the market and are applied in clinical practice. These algorithms could provide guidance for selecting the best metabolic strategy with the aim at reducing human error and optimizing management.

High-level psychotropic polypharmacy: a retrospective comparison of children in foster care to their peers on Medicaid

Background The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits. Methods A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration. Results High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015–2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate. Conclusions Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.

Clinical audit of cardio-metabolic monitoring in people with intellectual disability (PWID) taking antipsychotic medication

AimsTo ensure close monitoring of physical health parameters when antipsychotics are prescribed and to liaise with primary care to ensure appropriate interventions are implemented.BackgroundAntipsychotics are the most frequently prescribed psychotropic medication for PwID. Treatment with antipsychotic agent is associated with cardio-metabolic risks such as obesity, diabetes, and dyslipidemia. A strong association is well documented between antipsychotic use and the risk of stroke in schizophrenia although the magnitude of this association has yet to be studied in PwID.PwID have an increased risk of premature death. Cardio-metabolic monitoring and appropriate intervention to this vulnerable cohort will improve the preventable cardio-metabolic multi-morbidity. The NICE guideline (CG11) recommends antipsychotic medication should only be initially prescribed and monitored by the secondary care professionals for at least 12 months. They also should work together with primary care to ensure appropriate interventions are arranged where necessary.MethodA retrospective audit was performed for 40 service users, taking antipsychotic medication. Quota sampling was used to identify 10 cases each from the caseload of 4 consultant psychiatrists, within the Intellectual Disability community setting, between September 2019 and October 2019.An audit tool was designed, in accordance with cardio-metabolic measures (smoking status, height, weight, Blood Pressure, HbA1c, Lipid profile), based on physical health CQUIN targets and the Lester adaptation tool. Collection of data was performed from electronic case records and electronic blood results service. The work was performed with the approval of local clinical audit team and analysed by using Microsoft Excel.ResultBaseline cardio-metabolic assessment was observed in over a half of the sample population (50–65%) whilst only less than 15% was noted at 3–6 months. Documentation Evaluation of physical health assessments for new admissions to the Oleaster during the first wave of COVID-19 on body weight and blood pressure was seen only in 15% and 2.5% of population respectively at 3–6 months. Collaboration with GP for annual health check was observed in 78–100% of population.Intriguingly, our finding indicates a significant improvement in all required compliance when nursing team is involved.ConclusionImproving physical healthcare is essential to reduce the cardio metabolic outcome in PwID taking antipsychotic medication. Better involvement of community nurses as well as availability of Sphygmomanometers at every outpatient clinic will determine the successful implementation of cardio metabolic monitoring and effective collaboration with primary care clinicians.Once the action plan is disseminated to the teams, the impact of change will be reassessed by a re-audit in one year's time.

Audit on prolactin monitoring for patients on oral risperidone, intramuscular risperidone, and intramuscular paliperidone

AimsThe aim of this audit was to investigate whether sufficient Prolactin monitoring was completed in a patient sample in the Torfaen area of Aneurin Bevan University Health Board. This audit targetted patients an oral or intra-muscular formulation of Risperidone in the year 2018 with the hypothesis that Prolactin monitoring is done less frequently than recommended.BackgroundRisperidone is the anti-psychotic drug most frequently associated with hyperprolactinemia which is often asymptomatic but can present with symptoms of oligomenorrhea, amenorrhea, galactorrhea, decreased libido, infertility, and decreased bone mass in women. Men with hyperprolactinemia may present with erectile dysfunction, decreased libido, infertility, gynecomastia, decreased bone mass, and rarely galactorrhea. The BNF advises monitoring of Prolactin at baseline, after 6 months, and then annually.MethodRetrospective review of 150 patients’ clinical letters to identify if they are on the above medications, using the local digital records system EPEX. Emails were also sent to community psychiatric nurses asking them if they could highlight any patients they were caseholding on the above medication. Depot clinic lists were also examined. Patients identified as being on the above medication had their blood tests reviewed on the online system Clinical Workstation (CWS) to determine whether they had their Prolactin level tested. A single spot sample of all patients on Talygarn ward in January 2019 was also included.Result1. 28 Risperidone2. 23 of 28 never had any Prolactin measurements3. 2 of 28 patients had the appropriate level of monitoring done for the year of 2018a. One patient complained of Galacotorrheab. Another patient had baseline done while on the ward and isn't due for any further monitoring at the time of writing.ConclusionThe above results identify that Prolactin monitoring is not being routinely completed for patients on the studied medication at an acceptable compliance level. Limitations around utitlity of prolactin monitoring may be the contributing factors; eg. Prolactin levels or medication dose may not be positively associated with adverse effects.. Further efforts were made to highlight the importance of baseline prolactin monitoring, as well as including a baseline Prolactin as an admission blood test for patients presenting with psychotic symptoms or on an anti-psychotic. A complete audit of metabolic monitoring and Prolactin levels for all patients on anti-psychotics would be an appropriate next step.