Clinical components and associated behavioural aspects of a complex healthcare intervention : Multi-methods study of selective decontamination of the digestive tract in critical care

Copyright © 2013 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.Peer reviewedPostprin

Medication errors: a prospective cohort study of hand-written and computerised physician order entry in the intensive care unit

INTRODUCTION: The study aimed to compare the impact of computerised physician order entry (CPOE) without decision support with hand-written prescribing (HWP) on the frequency, type and outcome of medication errors (MEs) in the intensive care unit. METHODS: Details of MEs were collected before, and at several time points after, the change from HWP to CPOE. The study was conducted in a London teaching hospital's 22-bedded general ICU. The sampling periods were 28 weeks before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist prospectively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods, during the course of his normal chart review. RESULTS: The total proportion of MEs was significantly lower with CPOE (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036 prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time following the introduction of CPOE (p < 0.001). Two errors with CPOE led to patient harm requiring an increase in length of stay and, if administered, three prescriptions with CPOE could potentially have led to permanent harm or death. Differences in the types of error between systems were noted. There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined (p = 0.01). The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods (19.4 versus 20.0, respectively, p = 0.71). CONCLUSION: Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score (if intercepted errors were included). Moderate and major errors, however, remain a significant concern with CPOE

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients

BACKGROUND: It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% fT>1-4×MIC). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes. OBJECTIVES: The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobactam with a hollow-fibre infection model (HFIM). The second aim was to predict whether these PK/PD targets are currently achieved in critically ill patients through PK/PD model simulation. PATIENTS AND METHODS: A dose-fractionation study comprising 21 HFIM experiments was performed against a range of Gram-negative bacterial pathogens, doses and infusion times. Clinical data and dose histories from a case series of nine patients with a known bacterial infection treated with piperacillin/tazobactam in the ICU were collected. The PK/PD index and predicted plasma concentrations and therefore target attainment of the patients were simulated using R version 4.2.1. RESULTS: fT >MIC was found to be the best-fitting PK/PD index for piperacillin/tazobactam. Bactericidal activity with 2 log10 cfu reduction was associated with 77% fT>MIC. Piperacillin/tazobactam therapy was defined as clinically 'ineffective' in ∼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2  log10 cfu reduction was not attained. CONCLUSIONS: Our dose-fractionation study indicates an optimal PK/PD target in piperacillin/tazobactam therapies should be 77% fT>MIC for 2 log10 kill. Doses to achieve this target should be considered when treating patients in ICU

Selective decontamination of the digestive tract in critically ill patients treated in intensive care units: a mixed-methods feasibility study (the SuDDICU study)

Background: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Critically ill patients in intensive care units (ICUs) are particularly susceptible to these infections. One intervention that has gained much attention in reducing HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of intravenous (i.v.) antibiotics. SDD may reduce infections and improve mortality, but has not been widely adopted in the UK or internationally. Hence, there is a need to identify the reasons for low uptake and whether or not further clinical research is needed before wider implementation would be considered appropriate. Objectives: The project objectives were to (1) identify and describe the SDD intervention, (2) identify views about the evidence base, (3) identify acceptability of further research and (4) identify feasibility of further randomised controlled trials (RCTs). Design : A four-stage approach involving (1) case studies of two ICUs in which SDD is delivered including observations, interviews and documentary analysis, (2) a three-round Delphi study for in-depth investigation of clinicians' views, including semi-structured interviews and two iterations of questionnaires with structured feedback, (3) a nationwide online survey of consultants in intensive care medicine and clinical microbiology and (4) semistructured interviews with international clinical triallists to identify the feasibility of further research. Setting : Case studies were set in two UK ICUs. Other stages of this research were conducted by telephone and online with NHS staff working in ICUs. Participants : (1) Staff involved in SDD adoption or delivery in two UK ICUs, (2) ICU experts (intensive care consultants, clinical microbiologists, hospital pharmacists and ICU clinical leads), (3) all intensive care consultants and clinical microbiologists in the UK with responsibility for patients in ICUs were invited and (4) international triallists, selected from their research profiles in intensive care, clinical trials and/or implementation trials. Interventions : SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of i.v. antibiotics. Main outcome measures: Levels of support for, or opposition to, SDD in UK ICUs; views about the SDD evidence base and about barriers to implementation; and feasibility of further SDD research (e.g. likely participation rates). Results : (1) The two case studies identified complexity in the interplay of clinical and behavioural components of SDD, involving multiple staff. However, from the perspective of individual staff, delivery of SDD was regarded as simple and straightforward. (2) The Delphi study (n = 42) identified (a) specific barriers to SDD implementation, (b) uncertainty about the evidence base and (c) bimodal distributions for key variables, e.g. support for, or opposition to, SDD. (3) The national survey (n = 468) identified uncertainty about the effect of SDD on antimicrobial resistance, infection rates, mortality and cost-effectiveness. Most participants would participate in further SDD research. (4) The triallist interviews (n = 10) focused largely on the substantial challenges of conducting a large, multinational clinical effectiveness trial. Conclusions : There was considerable uncertainty about possible benefits and harms of SDD. Further large-scale clinical effectiveness trials of SDD in ICUs may be required to address these uncertainties, especially relating to antimicrobial resistance. There was a general willingness to participate in a future effectiveness RCT of SDD. However, support was not unanimous. Future research should address the barriers to acceptance and participation in any trial. There was some, but a low level of, interest in adoption of SDD, or studies to encourage implementation of SDD into practice

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Reducing medication errors in critical care patients:pharmacist key resources and relationship with medicines optimisation

Abstract Background Medication errors are the most common type of medical errors critical care patients experience. Critical care units utilise a variety of resources to reduce medication errors; it is unknown which resources or combinations thereof are most effective in improving medication safety. Objectives To obtain UK critical care pharmacist group consensus on the most important interventions/resources that reduce medication errors. To then classify units that participated in the PROTECTED UK study to investigate if there were significant differences in the reported pharmacist prescription intervention type, clinical impact and rates according to unit resource classification. Methods An e-Delphi process (three rounds) obtained pharmacist consensus on which interventions/resources were most important in the reduction of medication errors in critical care patients. The 21 units involved in the PROTECTED UK study (multicentre study of UK critical care pharmacist medicines interventions), were categorised as high-, medium- and low-resource units based on routine delivery of the final Top 5 interventions/ resources. High and low units were compared according to type, clinical impact and rate of medication interventions reported during the PROTECTED UK study. Key findings Consensus on the Top 5 combined medication error reduction resources was established: advanced-level clinical pharmacist embedded in critical care being ranked most important. Pharmacists working on units with high resources made significantly more clinically significant medicines optimisations compared to those on low-resourced units (OR 3.09; P = 0.035). Conclusions Critical care pharmacist group consensus on the most important medication error reduction resources was established. Pharmacists working on high-resourced units made more clinically significant medicines optimisations. </jats:sec

An analysis of medicine costs of adult patients on a critical care unit

PurposeTo evaluate the costs of medicines used to treat critically ill patients in an intensive care environment and to correlate this with severity of illness and mortality.Materials and MethodsThe study was conducted at a London Teaching Hospital Critical Care Unit. Data were collected for patients who were either discharged or died during September 2011 and stayed longer than 48 hours. The drug cost was related to 150 drugs that were then related to patient's acuity and outcome.ResultsThe median daily drug cost of the 85 patients was £26. The highest cost patients in the 85th percentile had significantly higher daily drug costs (median, £403) and higher scores for patient acuity. Patients with hematologic malignancy had a median daily drug cost (£561) more than 20 times higher than those without. A regression analysis based on patient's diversity explained 93% of the variance in the daily drug cost.ConclusionsAlthough the median daily drug cost for an adult critically ill patient was low, this cost significantly escalated with patient acuity and hematologic malignancy. A reference method has been designed for an in-depth evaluation of daily drug cost that could be used to compare expenditure in other units

Medication issues experienced by patients and carers after discharge from the intensive care unit

Purpose: Medication-related problems (MRPs) frequently occur at the interfaces of care settings. We examined this further because little has been published about MRPs experienced by patients/carers after discharge from the intensive care unit (ICU). Methods and Materials: Medication history data were collected before, during, and after ICU admission and by face-to-face semistructured interviews with 21 patients and 13 carers attending the ICU Follow-up Clinic (FC) of our 35-bed adult ICU. Results: A total of 122 drugs were prescribed regularly before ICU admission, 168 on ICU discharge, 132 at hospital discharge, and 128 at the FC. Medication-related problems were identified with hypnotics/anxiolytics, antidepressants, proton pump inhibitors, and analgesics. Good follow-up was observed in all 4 cases where the antidysrhythmic agent amiodarone was initiated on ICU. Patients/carers described 20 cases of difficulty in obtaining appropriate and timely supplies and 19 of insufficient information. Conclusions: These results show that our incidence of MRPs after ICU discharge was encouragingly infrequent, in which we attribute it to targeted medicine reconciliation and the availability of our FC. However, MRPs were perceived to stem from inadequate communication at the interfaces of care and the lack of opportunity for patients/carers to obtain relevant information. We recommend that FC should focus on MRPs during their consultation and that further research in this area should be performed to examine our observations further. © 2013 Elsevier Inc