Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

BACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.

Haematological point of care testing for clozapine monitoring.

BACKGROUND: Clozapine treatment requires regular full blood counts (FBC) because of the risk of agranulocytosis. Traditionally, FBCs use venous blood samples but the need for frequent venepuncture adversely affects adherence. We investigated the utility of a point of care testing (POCT) finger prick method for clozapine patients. METHOD: Patients being treated with clozapine, who were having a venous blood sample taken for haematological monitoring, also provided a fingerprick capillary blood sample. The PixCell HemoScreen® POCT analyser was used to test both the capillary and venous samples, and the venous sample was also tested using a standard laboratory method. RESULTS: We completed FBCs on 226 patients. We found strong correlations between the results from the standard laboratory venous method and the POCT capillary and venous assays for WBC (R = 0.96 & R = 0.99), neutrophils (R = 0.96 & R = 0.97) and eosinophils (R = 0.94 & R = 0.94). Compared with the standard laboratory venous blood method, mean biases for capillary blood POCT method were -0.56 × 109/L for WBC, -0.39 × 109/L for neutrophils, and -0.01 × 109/L for eosinophils. Mean biases for venous blood POCT method were -0.004 × 109/L for WBC, -0.28 × 109/L for neutrophils, and 0.01 × 109/L for eosinophils. Of the 226 patients tested, 10 (4.4%) had levels below clozapine monitoring thresholds (WBC <3.5 × 109/L and Neutrophils <1.5 × 109/L) by capillary blood, and 4 (1.8%) by venous blood by POCT. The standard laboratory method showed 3 of these to be sub-threshold. All cases of neutropenia were identified by capillary and venous POCT. CONCLUSION: The PixCell HemoScreen® POCT analyser provided results that were comparable with those from a standard venous blood laboratory method for WBC, neutrophil and eosinophil counts. The availability of an accurate capillary monitoring method may result in increased clozapine uptake and better clozapine adherence.