Hospital pharmacists' opinions on a risk prediction tool for medication-related harm in older people.

AIM: Older adults are particularly affected by medication-related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk-prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME-RPT. METHODS: Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case-vignettes each with a calculated PRIME-RPT score to help guide discussion. Case-vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a "framework" approach. RESULTS: Seven themes emerged in relation to the PRIME-RPT: (1) providing a medicine-prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow-up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations. CONCLUSION: Hospital pharmacists found the PRIME-RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.

Characterising older adults' risk of harm from blood-pressure lowering medications: a sub-analysis from the PRIME study.

AIM: Cardiovascular disease (CVD) is common amongst frail older people. The evidence base for CVD commonly excludes older adults with multimorbidity or chronic conditions. Most cardiovascular drugs have the potential to lower blood pressure (BP) and therefore cause medication-related harm (MRH). We aimed to identify key clinical and sociodemographic characteristics associated with MRH in older people taking BP-lowering drugs for whatever indication they were prescribed. METHODS: The PRIME (prospective study to develop a model to stratify the risk of MRH in hospitalised elderly patients in the UK) study investigating the incidence and cost of MRH in older people across Southern England. Adults ≥65 years were recruited from five teaching hospitals at hospital discharge and followed up for 8 weeks. Telephone interviews with study participants, review of primary care records and hospital readmissions were undertaken to identify MRH. PRIME study participants taking BP-lowering drugs (as defined by National Institute for Health and Care Excellence hypertension guidelines) were included in this analysis. RESULTS: One hundred and four (12%) study patients experienced a total of 153 MRH events associated with BP-lowering drugs. Patients on four BP-lowering drugs were five times more likely to experience MRH compared to those taking one medication (OR 4.96; 95%CI 1.63-15.13; P = 0.01). Most MRH events were classified 'serious' (80%, n = 123), requiring dose change or treatment cessation. Almost half of MRH were potentially preventable (49%, n = 75). CONCLUSION: Polypharmacy from BP-lowering drugs in older people is associated with preventable harm. Decisions around cardiovascular risk reduction should be carefully considered in view of MRH arising from BP-lowering drugs.

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy.

OBJECTIVES: To determine the association between frailty and medication-related harm requiring healthcare utilisation. DESIGN: Prospective observational cohort study. SETTING: Six primary and five secondary care sites across South East England, September 2013-November 2015. PARTICIPANTS: One thousand and two hundred and eighty participants, ≥65 years old, who were due for discharge from general medicine and older persons' wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained. MAIN OUTCOME MEASURES: Medication-related harm requiring healthcare utilisation (including primary, secondary or tertiary care consultations related to MRH), including adverse drug reactions, non-adherence and medication error determined via the review of data from three sources: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of readmission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing number of medicines and frailty. RESULTS: Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06-49.26, P = 0.004), independent of age, gender, and number of medicines. With increasing frailty, the need for healthcare use as a result of MRH increases from a probability of around 0.2-0.4. This is also the case for the number of medicines. CONCLUSIONS: Frailty is associated with MRH, independent of polypharmacy. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.

The Association of a Single-Nucleotide Polymorphism in the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene With Adverse Drug Reactions, Multimorbidity, and Frailty in Older People.

Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human aging, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates a cell's response to stressors, including the expression of enzymes involved in drug metabolism. Its expression has been shown to decline in animal aging models. In this study, we tested the hypothesis that Nrf2 gene (NFE2L2) transcription/translation decline in human aging and that single-nucleotide polymorphisms (SNPs) in the NFE2L2 gene are associated with increased ADR risk, multimorbidity, and frailty in older people. Gene expression and protein levels were measured in peripheral blood mononuclear cells donated from healthy patients aged 18-80 years old. NFE2L2 genotypes were determined at three loci in a subpopulation of patients recruited to the PRIME study (a multicenter prospective cohort study that followed older adults for 8 weeks post-discharge to determine ADR). Both NFE2L2 gene and Nrf2 protein expression declined significantly with age in human peripheral blood mononuclear cells. In the PRIME substudy population, the rs35652124 NFE2L2 SNP was associated with increased ADR risk and decreased frailty and multimorbidity scores.

Medication-related harm: a geriatric syndrome.

The WHO Global Patient Safety Challenge: Medication Without Harm recognises medication-related harm (MRH) as a global public health issue. Increased life-expectancy coupled with multimorbidity and polypharmacy leads to an increased incidence of MRH, especially in older adults: at a cost of approximately £400 million to the National Health Service (NHS) in England. Harm from medicines has long been recognised by geriatricians, and strategies have been developed to mitigate harm. In general, these have focused on the challenges of polypharmacy and appropriateness of medicines, but impact on the quality of life, clinical and economic outcomes has been variable and often disappointing. The problem of MRH in older adults will continue to grow unless a new approach is adopted. Emerging evidence suggests that we need to take a broader approach as described in our conceptual model, where well-recognised physiological changes are incorporated, as well as other rarely considered psychosocial issues that influences MRH. Parallels may be drawn between this approach and the management of geriatric syndromes. We propose there must be a greater emphasis on MRH, and it, of itself, should be considered as a geriatric syndrome, to bring the spotlight onto the problem and to send a clear signal from geriatric experts that this is an important issue that needs to be addressed using a co-ordinated and tailored approach across health and social care boundaries. This requires a more proactive approach to monitor and review the medicines of older adults in response to their changing need.

Do the 2015 Beers Criteria predict medication-related harm in older adults? Analysis from a multicentre prospective study in the United Kingdom.

PURPOSE: To investigate whether inappropriate prescribing, defined by the Beers Criteria, is associated with medication-related harm (MRH), hospital admission, and mortality in older adults in England. METHODS: A multicentre, prospective cohort study recruited 1280 patients (median age 82 years) at hospital discharge. Patients were followed-up in the community by pharmacists for 8 weeks to identify MRH (harm from adverse drug reactions, non-adherence, and medication errors) and hospital admissions. One-year mortality was determined using hospital records. Potentially inappropriate medications (PIMs) were determined using the 2015 version of the Beers criteria. Logistic regression was used to investigate the relationship between patients prescribed PIMs and adverse outcomes. RESULTS: Two hundred and seventy-six patients (22%) were prescribed one or more PIMs at hospital discharge. The main PIM classes prescribed at hospital discharge were benzodiazepines and related drugs (30%) and antidepressants (27%). 1116 out of 1280 patients completed follow-up and 413 (37%) experienced MRH. In 51 cases (12%), MRH was attributable to a PIM. There was no significant relationship between patients prescribed PIMs and overall MRH, hospital readmission or all-cause one-year mortality. Multiple PIMs at discharge was independently associated with an increased risk of ADR (OR 2.32, 95% CI 1.03-5.23). CONCLUSION: The prescribing of PIMs is common at hospital discharge of older adults in England. The 2015 Beers criteria have a limited clinical value to predict adverse outcomes following hospital discharge in this setting.

Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

Supply of unlicensed medicines to children: semi-structured interviews with carers.

OBJECTIVES: To explore the experiences of parents and carers relating to the supply of unlicensed medicines for their child after discharge from hospital. METHODS: Semi-structured interviews were conducted with 15 parents and carers of children who were newly prescribed an unlicensed medicine. Interviews were conducted at least 4 weeks after the child's discharge from hospital. Qualitative thematic analysis of the data was carried out. RESULTS: Problems were frequently encountered by parents when attempting to obtain further supplies of their child's unlicensed medicine. Problems included general practitioners (GPs) refusing to prescribe the medicine, GPs prescribing a dose or formulation that differed to what had been prescribed previously, pharmacists who were unable to source a suitable medicine, medicines that were not labelled with administration instructions and delays in obtaining the medicine. Action or intervention by the parent was often required to overcome the problems faced. The necessity of these actions or interventions, and the implication of not succeeding, frequently caused parents anxiety, frustration and dissatisfaction. CONCLUSIONS: Strategies for improving the process of medicine supply during the transition between secondary and primary care are necessary and must involve greater communication among healthcare professionals and carers. GPs and community pharmacists should have access to greater support and guidance to facilitate the safe prescribing and supply of unlicensed medicines. Parents and carers should be informed about the process to ensure understanding, create empowerment and to build relationships between them and the professionals responsible for the care of their child.

Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

BACKGROUND: Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67-0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks. CONCLUSIONS: DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.

Dosing regimen of meropenem for adults with severe burns: a population pharmacokinetic study with Monte Carlo simulations.

OBJECTIVES: To develop a population model to describe the pharmacokinetics (PK) of intravenous meropenem in adult patients with severe burns and investigate potential relationships between dosage regimens and antimicrobial efficacy. PATIENTS AND METHODS: A dose of 1 g every 8 h was administered to adult patients with total body surface area burns of ≥15%. Doses for subsequent courses were determined using results from the initial course and the patient's clinical condition. Five plasma meropenem concentrations were typically measured over the dosage interval on one to four occasions. An open, two-compartment PK model was fitted to the meropenem concentrations using NONMEM and the effect of covariates on meropenem PK was investigated. Monte Carlo simulations investigated dosage regimens to achieve a target T>MIC for ≥40%, ≥60% or ≥80% of the dose interval. RESULTS: Data comprised 113 meropenem concentration measurements from 20 dosage intervals in 12 patients. The parameters were CL (L/h) = 0.196 L/h/kg × [1 - 0.023 × (age - 46)] × [1 - 0.049 × (albumin - 15)], V1 = 0.273 L/kg × [1 - 0.049 × (albumin - 15)], Q = 0.199 L/h/kg and V2 = 0.309 L/kg × [1 - 0.049 × (albumin - 15)]. For a target of ≥80% T>MIC, the breakpoint was 8 mg/L for doses of 1 g every 4 h and 2 g every 8 h given over 3 h, but only 4 mg/L if given over 5 min. CONCLUSIONS: Although 1 g 8 hourly should be effective against Escherichia coli and CoNS, higher doses, ideally with a longer infusion time, would be more appropriate for empirical therapy, mixed infections and bacteria with MIC values ≥4 mg/L.

What do healthcare providers know about nutrition support? A survey of the knowledge, attitudes, and practice of pharmacists and doctors toward nutrition support in Malaysia.

BACKGROUND AND AIMS: Malnutrition is one of the health problems that can be prevented by appropriate nutrition care provided by healthcare providers. However, this practice is still lacking possibly because of the providers' inadequate knowledge. The aim of this study was to evaluate the self-reported knowledge, attitudes, and practices of pharmacists and doctors toward nutrition support in a tertiary care hospital setting. METHODS: A validated questionnaire was distributed to all the doctors and pharmacists working in a tertiary hospital in Penang, Malaysia. Seven individuals including academics, general surgeons, and pharmacists performed the face and content validity. The questionnaire was piloted using 24 healthcare providers at a different hospital. RESULT: Of 400 surveyed, 158 doctors and 72 pharmacists from various grades completed the questionnaire. More doctors (31.6%) than pharmacists (15.3%) reported adequate knowledge to perform patients' nutrition screening. However, in the knowledge assessment, pharmacists had a higher mean score (6.07 ± 1.77) than the doctors did (4.59 ± 1.87; P < .001), and most (70.4%) of them were grouped in the "average" score range. In addition, both pharmacists and doctors have ambivalent attitudes toward nutrition support. Only 31.3% stated that they perform nutrition screening on admission, and half of them performed nutrition assessment during hospitalization. CONCLUSION: Inappropriate nutrition care might be due to the lack of guidelines and insufficient knowledge among doctors and pharmacists. Special nutrition training and education for both pharmacists and doctors should be established.

Changes in thrombin generation and D-dimer concentrations in women injecting enoxaparin during pregnancy and the puerperium.

BACKGROUND: It is well accepted that the gravid state is hypercoagulable and a significant cause of both maternal morbidity and mortality in the Western world. Although thrombin generation is reported to be increased in pregnant women, uncertainty exists on the pattern of thrombin generation change during this time. The aim of this study is to describe thrombin generation changes and D-dimer concentrations in women injecting enoxaparin during pregnancy the postnatal period. METHODS: One hundred and twenty-three women injecting enoxaparin had their thrombin generation, as measured by Calibrated Automated Thombinography (CAT), repeatedly assayed during pregnancy, once in each trimester, at delivery and 8 weeks post-partum. Furthermore, to understand the impact enoxaparin has on D-dimer concentrations during pregnancy, D-dimer concentrations were measured monthly in the recruited women. RESULTS: Thrombin generation was found to increase in the first trimester (mean endogenous thrombin potential (ETP): 1391 nmol/L.min), further increasing during the second trimester (mean ETP: 1757 nmol/L.min), after which it plateaued through to delivery, where it peaked (mean ETP: 1857 nmol/L.min) and then fell back at 8 weeks post-partum (ETP: 1293 nmol/L.min). In contrast D-dimer concentrations increased exponentially during the antenatal period, despite the enoxaparin prescription. CONCLUSION: Our results provide further evidence on alterations of thrombin generation during pregnancy and the postnatal period.

Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models.

Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR.

Population pharmacokinetics of enoxaparin during the antenatal period.

BACKGROUND: The optimal dosing strategy of low-molecular-weight heparins for the treatment of antenatal venous thromboembolism is not known. The physiological changes associated with pregnancy alter the pharmacokinetic profile of low-molecular-weight heparins, which has led to controversy and subsequent variation in practice, when pregnant women with venous thromboembolism are treated with low-molecular-weight heparins. Our objective was to develop a robust pharmacokinetic model of enoxaparin during the antenatal period to address this problem. METHOD AND RESULTS: Women prescribed antenatal enoxaparin were eligible to enroll in the study. Recruited women were reviewed monthly and had up to 3 anti-Xa activities (trough and 1 and 3 hours after dose) drawn at each clinic attendance. Compartmental pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling. One hundred twenty-three patients contributed 795 anti-Xa activities for pharmacokinetic modeling purposes. Both enoxaparin clearance and volume of distribution were increased during pregnancy. Simulations of once- versus twice-daily enoxaparin administration demonstrated that both dosing regimens would reach target 3-hour plasma concentrations throughout the duration of the pregnancy. When trough anti-Xa activity was simulated, both once- and twice-daily regimens exhibited an increase in trough anti-Xa activity with the progression of pregnancy. This is explained by the significant increase in volume of distribution observed during pregnancy. CONCLUSIONS: The half-life of enoxaparin is prolonged with the progression of pregnancy, and our work provides compelling evidence for prescribing once-daily enoxaparin for the treatment of antenatal venous thromboembolism. National and international guideline recommendations should be reconsidered.

Adverse drug reactions in a population of hospitalized very elderly patients.

OBJECTIVES: The aims of the study were to determine the rates, types, severity and preventability of adverse drug reactions (ADRs) in a hospitalized population of very elderly patients (over 80 years of age) and to identify factors that predispose the very elderly to an ADR. METHODS: An observational study was conducted in patients over 80 years of age admitted to four care of the elderly wards in Brighton and Sussex University Hospitals NHS Trust. The main outcome measures were the incidence of ADRs during inpatient stay in older patients and the identification of the major drug classes involved and the risk factors contributing to the occurrence of ADRs. RESULTS: A total of 560 very elderly patients were recruited, 74 of whom experienced one or more ADR (83 in total), representing an incidence of 13.2% (95% CI 10.4, 16). Sixty-three percent of all ADRs were considered preventable, with 57 classified as serious and three as life threatening. The drug classes frequently implicated in ADRs were cardiovascular agents (34%), analgesic medications (18%) and anti-diabetic drugs (10%). Five variables were established as independent predictors of ADRs: number of medications, use of hypoglycaemic agents, history of hyperlipidaemia, raised white cell count on admission, and length of stay. CONCLUSIONS: The ADR incidence reported in this population was no greater than that seen in other studies for both general medical patients and those elderly patients over 65 years of age. A significant proportion of ADRs were preventable, and this suggests that closer monitoring of high-risk elderly patients is needed to address this problem.

An evaluation of using multi-source feedback (MSF) among junior hospital pharmacists.

OBJECTIVE: The mini Peer Assessment Tool (mini-PAT) for pharmacists was introduced in 2006 as a formative method of assessing junior hospital pharmacists in the workplace and is the first widespread application of multi-source feedback (MSF) specifically within a pharmacy setting. The aim of this study was to evaluate the feasibility and measurement characteristics of the assessment method, in order to guide its future application. METHODS: At the time of the study (September 2008) the assessment had been in place for 3 years. All assessment data from the first 3 years were analysed retrospectively. KEY FINDINGS: We evaluated 633 mini-PAT assessments. Over the study period, the assessor response rate remained relatively consistent at 77% and compared favourably with applications of MSF within medicine. Members of the pharmacy team (pharmacists and pharmacy technicians) dominated the assessor nomination lists. It was encouraging to see completed assessment forms returned from nominated doctors and nurses with whom the junior pharmacist had been working. Differences were found between how different occupational groups rated the junior pharmacists against the 16 items on the assessment form (Kruskal-Wallis, df=3, P<0.001). Pharmacist assessors rated the junior pharmacists lowest against all 16 items on the mini-PAT assessment form, whereas nominated doctors rated them the highest. CONCLUSION: This study demonstrates that an MSF assessment method can successfully be applied to a wide range of junior hospital pharmacists, and that the majority of junior hospital pharmacists assessed meet expectations.

Understanding vs. competency: the case of accuracy checking dispensed medicines in pharmacy.

Ensuring the competence of healthcare professionals' is core to undergraduate and post-graduate education. Undergraduate pharmacy students and pre-registration graduates are required to demonstrate competence at dispensing and accuracy checking medicines. However, competence differs from understanding. This study determined the competence and understanding of undergraduate students and pharmacists at accuracy checking dispensed medicines. Third year undergraduate pharmacy students and first year post-graduate diploma pharmacists participated in the study, which involved an accuracy checking task and concept mapping exercise. Participants accuracy checked eight medicines which contained 13 dispensing errors and then constructed a concept map illustrating their understanding of the accuracy checking process. The error detection rates and types of dispensing errors detected by undergraduates and pharmacists were compared using Mann-Whitney and chi-square, respectively. Statistical significance was p ≤ 0.05. Concept maps were qualitatively analysed to identify structural typologies. Forty-one undergraduates and 78 pharmacists participated in the study. Pharmacists detected significantly more dispensing errors (85%) compared to the undergraduates (77%, p ≤ 0.001). Only one undergraduate and seven pharmacists detected all dispensing errors. The majority of concept maps were chains (undergraduates = 46%, n = 19; pharmacists = 45%, n = 35) and spokes (undergraduates = 54%, n = 22; pharmacists = 54%, n = 42) indicating surface learning. One pharmacist, who detected all dispensing errors in the accuracy checking exercise, created a networked map characteristic of deep learning. Undergraduate students and pharmacists demonstrated a degree of operational competence at detecting dispensing errors without fully understanding the accuracy checking process. Accuracy checking training should be improved at undergraduate and post-graduate level so that pharmacists are equipped with the knowledge and understanding to accurately check medicines and detect dispensing errors, thereby safeguarding patient safety.

Inflammatory cytokine removal by an activated carbon device in a flowing system.

A prototype in-line filtration/adsorption device has been developed using novel synthetic pyrolysed carbon monoliths with controlled mesoporous domains of 2-50nm. Porosity was characterized by SEM and porosimetry. Removal of inflammatory cytokines TNF, IL-6, IL-1beta and IL-8 was assessed by filtering cytokine spiked human plasma through the walls of the carbon modules under pressure. The effect of carbon filtration on plasma clotting response and total plasma protein concentration was also assessed. Significant removal of the cytokines IL-6, IL-1beta and IL-8 was observed. Initially marked TNF removal diminished over time. The coagulation studies indicated that the carbon device does not exacerbate the propensity of blood plasma to clot. The total plasma protein concentration remained constant. The device offers a broader approach to the treatment of systemic inflammatory response syndrome (SIRS) by the removal of inflammatory mediators central to its progression.

The in vitro adsorption of cytokines by polymer-pyrolysed carbon.

This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.