Although intestinal metabolism plays an important role in drug disposition, early predictions of human outcomes are challenging, in-part due to limitations of available in vitro models. To address this, we have evaluated three in vitro models of human intestine (microsomes, permeabilized enterocytes, and cryopreserved intestinal mucosal epithelium) as tools to assess intestinal metabolism and estimate the fraction escaping gut metabolism (f g) in drug discovery. The models were tested with a chemically diverse set of 32 compounds, including substrates for oxidoreductive, hydrolytic, and conjugative enzymes. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) was used to quantify substrate disappearance (CL int) and qualify metabolite formation (QuanQual). Fraction unbound in the incubation (f u,inc) was determined by rapid-equilibrium dialysis (RED). Measured in vitro results [intrinsic clearance (CL int) and f u,inc ] were supplemented with literature data [passive Caco-2 A→B permeability, enterocyte blood flow (Q ent), and intestinal surface area (A)] and combined using a midazolam-calibrated Q gut model to predict human f g values. All three models showed reliable cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) activities, but enterocytes and mucosa may offer advantages for low clearance compounds and alternative pathways (e.g. sulfation, hydrolases, and flavin-containing monooxigenases). Early predictions of human f g values were acceptable for the high f g compounds (arbitrarily f g >0.7). However, predictions of low and moderate f g values (arbitrarily f g <0.7) remain challenging, indicating that further evaluation is needed (e.g. saturation effects and impact of transporters), but not immediate compound avoidance. Results suggest that tested models offer an additional value in drug discovery, especially for drug design and chemotype evaluation.

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The National Institute of Clinical Excellence (NICE) released new fluid guidelines following data suggesting 20% of patients receiving fluids suffer adversely (2013). This quality improvement group assessed fluid prescribing in a tertiary teaching centre and introduced a new fluid- prescribing chart to align practice with NICE recommendations.Notes and corresponding fluid prescription charts were reviewed for evidence of (1) indication, (2) co-morbidities, and (3) further management as surrogate markers of safe prescribing in accordance with NICE. Overall, the data showed practice fell short and prompted a redesign of the Trust fluid prescription chart. Three different variations of the chart were issued consecutively using a PDSA method (plan, do, study, act) over a 6-month period. They all included indication, co-morbidities and further management plans as constant design features. Suggestions from interested parties were incorporated and an educational programme was implemented to promote awareness.Prior to our intervention, an indication for fluids was documented in 26% of notes, it took an average of 4.6 minutes to find co-morbidities, and further management plans were rarely documented. Following the new prescription chart, an indication was recorded in 72% of cases, co-morbidities noted on 63% of charts with 93.1% accuracy, and further management documented in 100% of cases.The new fluid prescription chart encourages prescribers to incorporate NICE recommendations when prescribing fluids. The new fluid prescription design has since been rolled out Trust wide.

Clinicians can enable patients to actively participate in their care but communication with patients is often poor and highly variable. The aim of this study was to explore patients’ understanding of their current illness while in hospital and using a codesign process to create prototype tools to facilitate better communication during ward rounds.A mixed-methods, multistep design with step 1: Application of a questionnaire addressing domains of care in the acute medical unit; step 2: Development of communication aids that were codesigned with active help of patients, students and a specialist in user centric design to address patient needs and step 3: Evaluation of tools with patients in four Plan–Do–Study–Act cycles.In the initial survey of 30 patients 12 (40%) patients did not know what their diagnosis was and 5 (17%) did not know the results of recent key tests. 20 (67%) patients felt that staff communication and coordination could be improved.An intervention was prototyped with four variations: (1) An A6 ward-round summary sheet completed by doctors during ward rounds. The system worked well but was highly person dependent. (2) An A4 patient-owned diary (‘How to Hospital’) that contained information about key processes in hospital and space to document conversations from rounds and prompts for questions. 10 patients read the diary and commented favourably but did not complete any pages. (3) ‘Diary-cards’: a basic set of information cards was given to patients on admission to hospital. (4) Patient specific ‘diary-cards’ were completed by clinicians—10 forms were piloted during rounds and improved subsequent day information retention of diagnosis to 80%.Our study identified interventions that were feasible but remained person-dependent. The patients’ ownership of information in relation to their care might facilitate retention and satisfaction but the optimal format for these interventions for enhancing communication remains unclear.