Graham Davies

Pharmacokinetics of opioids in renal dysfunction

SummaryPatients with renal insufficiency commonly require the administration of an opioid analgesic to provide adequate pain relief. The handling of morphine, pethidine (meperidine) and dextropropoxyphene in patients with renal insufficiency is complicated by the potential accumulation of metabolites. While morphine itself remains largely unaffected by renal failure, accumulation, as denoted by an increase in both mean peak concentrations and the area under the concentration-time curve, of both the active metabolite (morphine-6-glucuronide) and the principal metabolite (morphine-3-glucuronide, thought to possess opiate antagonist properties) have been reported. The increased elimination half-lives of the toxic metabolites norpethidine and norpropoxyphene in patients with poor renal function administered pethidine and dextropropoxyphene, respectively, makes their routine use ill advised.Case reports of prolonged narcosis associated with the use of both codeine and dihydrocodeine in patients with renal insufficiency call for care to be used when prescribing these agents under such conditions. Although the pharmacokinetics of buprenorphine, alfentanil, sufentanil and remifentanil change little in patients with renal failure, the continuous administration of fentanyl can lead to prolonged sedation.

Complimentary and alternative medicine use among patients starting warfarin

The use of complimentary and alternative medicines (CAM) among the UK population is on the increase. For patients requiring warfarin therapy, it is important to maintain an adequate and safe level of anticoagulation. As some forms of CAM can interact with warfarin, it is imperative that any patient considered for warfarin, is asked about their use of CAM. Our report describes the incidence and type of CAM usage among patients about to start or recently commenced on warfarin therapy attending our outpatient anticoagulant clinic. All patients attending clinic for the first time were seen by a pharmacist. A retrospective analysis of the pharmaceutical care plans for all patients seen during 2003 were analysed regarding the degree of CAM usage. Of 631 care plans reviewed, 170 (26·9%) patients were taking some form of CAM. Ninety‐nine (58% of all CAM users) were taking a CAM that could interact with warfarin; the commonest forms were cod‐liver oil capsules and garlic capsules. We conclude that many patients new to warfarin therapy were significant users of CAM, many of which had the potential to interact with warfarin. By taking a full drug history, potential CAM/warfarin interactions could be avoided.

Use of oral clonidine for sedation in ventilated paediatric intensive care patients

Objectives We aimed to document our experience with oral clonidine when used as a sedative in combination with intravenous morphine and lorazepam in a group of mechanically ventilated children with single-organ, respiratory failure. In particular, our objectives were to establish the relationship between oral dose, plasma concentration, and sedative effect, and second, to document the side-effect profile.Design Prospective, cohort study over a 72-h period.Setting Regional paediatric intensive care unit.Patients and participants Twenty-four children were enrolled (median age 3xa0months) of whom ten were excluded (six due to extubation before 72xa0h, three sedation failures, one protocol violation).Measurements and results Plasma clonidine was measured using gas chromatography mass spectrometry, and sedation assessed using the COMFORT score. Using a dose of 3–5xa0μg/kg every 8xa0h, plasma concentrations appeared to plateau at approximately 41xa0h giving a mean value of 1.38xa0ng/ml (95% confidence interval 1.0–1.8). Adequate sedation was achieved during 82% (837/1022xa0h) of the study period; however, this decreased to 70.3% when analysed on an intention-to-treat basis. There was a concomitant overall decrease in the average hourly requirements for both morphine (P = 0.02) and lorazepam (P = 0.003). There were no documented episodes of bradycardia, hypotension or hyperglycaemia.Conclusions Oral clonidine may be a safe and effective sedative in combination with morphine and lorazepam for young children with single-organ, respiratory failure. This agent may also exhibit opioid and benzodiazepine sparing effects in this patient group. A full pharmacokinetic study is warranted.

Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model

Background Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. Methods We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). Results Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. Conclusions We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.

Immune Reconstitution and Recovery of FOXP3 (Forkhead Box P3)-Expressing T Cells After Transplantation for IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked) Syndrome

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is a rare X-linked disorder that usually presents in early childhood with immune enteropathy, diabetes mellitus, and other autoimmune complications. The disease is caused by mutations in the forkhead box P3 gene, a transcription factor that is essential for the development and function of regulatory T cells. This population of cells plays an essential role in controlling immune responses and preventing autoimmunity. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is often initially treated with immunosuppressive drugs, but only allogeneic hematopoietic stem cell transplantation has offered the possibility of cure. We recently performed an unrelated donor transplant in a child with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome by using a reduced-intensity conditioning regimen. This transplant provided a rare opportunity to gain valuable insight into the regeneration of the immune system after transplantation. Clinical recovery was associated with the emergence of regulatory T cell populations, the majority of which expressed memory phenotype markers and raised important questions about the origin and longevity of the FOXP3+ regulatory T cell pool.

The design and evaluation of a simulated‐patient teaching programme to develop the consultation skills of undergraduate pharmacy students

Objectives: This study aimed to identify the key skills and knowledge required for the delivery of an ideal patient consultation in order to develop a training programme (using simulated-patients) to teach consultation skills to undergraduate pharmacy students. Methods:Participants included all third year undergraduate Pharmacy students (MPharm, level III) at the School of Pharmacy & Biomolecular Sciences, University of Brighton (from October 1999 to March 2000). Working in groups of 12, students participated in two 4 hour seminars. A structured questionnaire was designed to assess students perceptions of the difficulty of conducting a consultation and their confidence in delivering a structured consultation. Main outcome measures: Questionnaires were administered before and after delivery of the teaching programme to assess changes in students confidence and ability to consult with patients.Results:Twelve volunteers satisfied the criteria set to serve as simulated patients and then received appropriate training. Six scenarios were developed which focused on the key skills and knowledge identified from the adherence and consultation skills literature. A total of 91 students participated in the programme (mean age=23 years, SD=4.5). Following participation in the programme students perceived confidence for conducting an effective consultation significantly increased (t=-5.9,p<0.01) while a statistically significant decrease was seen in students perceived level of difficulty when conducting a consultation (t=4.0, p<0.01).Conclusion: This study has shown that the use of a structured teaching programme improves students perceptions of their ability and confidence in conducting an effective consultation. Providing skills training around the consultation process, using simulated patients, provides pharmacists with a good framework around which to practice pharmaceutical care.

Differentiating midazolam over-sedation from neurological damage in the intensive care unit

IntroductionMidazolam is used routinely to sedate patients in the intensive care unit (ICU). We suspected that midazolam over-sedation was occurring in the ICU of the Guys and St. Thomas Trust and that it could be difficult to differentiate this from underlying neurological damage. A sensitive assay for detecting midazolam and 1-hydroxymidazolam glucuronide (1-OHMG) in serum was developed and applied in the clinical setting.MethodsIn the present study we evaluated a series of cases managed in a mixed medical, surgical and trauma ICU. Serum was collected from 26 patients who received midazolam, were slow to wake and in whom there was suspicion of neurological damage. Patient outcome was followed in terms of mortality, neurological recovery and neurological damage on discharge.ResultsOut of 26 patients, 13 had detectable serum levels of midazolam and/or 1-OHMG after a median of 67 hours (range 36–146 hours) from midazolam cessation. Of these 13 patients in whom midazolam/1-OHMG was detectable, 10 made a full neurological recovery. Of the remaining 13 patients with no detectable midazolam/1-OHMG, three made a full neurological recovery; 10 patients were subsequently found to have suffered neurological damage (P < 0.002), eight of whom died and two were discharged from the ICU with profound neurological damage.ConclusionThese findings confirm that prolonged sedation after midazolam therapy should be considered in the differential diagnosis of neurological damage in the ICU. This can be reliably detected by the assay method described. The effects of midazolam/1-OHMG persist days after administration of midazolam has ceased. After prolonged sedation has been excluded in this patient group, it is highly likely that neurological damage has occurred.

Improvement in Pharmacist's Performance Facilitated by an Adapted Competency-Based General Level Framework

The General Level Framework (GLF) is a tool for evaluating pharmacists performance, providing tailored feedback and training, and guiding professional development.

Evaluating clinical skills of undergraduate pharmacy students using objective structured clinical examinations (OSCEs)

Introduction: The objective structured clinical examination (OSCE) has been used for the competency assessment of clinical skills within the 4th year MPharm programme at the University of Brighton since 1999. Aim: To evaluate the clinical performance of 4th year MPharm students, through two academic years. Methods: Final year pharmacy undergraduate students were divided into 16 groups and completed an OSCE exam following a 1 week placement in a hospital. Each OSCE exam comprised of six workstations. Results: Significant differences were found between the students’ performances at the individual OSCE stations (Chi-square 1⁄4 40.7; df 1⁄4 5; p , 0.01). Students performed best on patient counselling stations and least on calculation and problem identification and resolution type stations. Conclusion: This study demonstrates that final year pharmacy undergraduates perform poorly in activities which demand an element of clinical problem identification and resolution or when performing a clinical calculation. These results suggest that a lack of clinical exposure may be, in part, responsible for the students’ perceived inability to deal with “real life” situations which involve clinical problem solving.

Academic Dishonesty Among Pharmacy Students

In previous studies, academic dishonesty was found to be common among pharmacy students. The aim of this investigation was to find the reasons for dishonest behaviour among pharmacy students. Twelve semi- structured interviews were carried out with first and fourth year pharmacy students, chosen to represent a broad spectrum of views about academic dishonesty. Five principle themes were identified as the motivations for student academic dishonesty: institutional environment, study skills, assessment employed, personal qualities and course specific factors. The results show that the motivational themes for dishonesty varied between the first year students and the fourth year students. The first year students interviewed, when compared to the fourth year students, were generally more uncertain about the definition of academic dishonestly, and consequently the behaviours associated with it. The first year students also appeared to possess poorer study skills and complained that the university failed to provide enough academic support. In contrast, the fourth year students interviewed were more sophisticated in their approach to academic dishonesty. They frequently mentioned pressure and stress as motivational factors leading some students to resort to dishonest behaviours. They were also more aware of the opportunities to engage in dishonest academic behaviour than first year students and generally believed engaging in dishonest behaviour was an institutional culture. All the students interviewed stated that engaging in dishonest behaviour could be motivated by peer pressure, fulfilling their social and esteem needs. Dishonest behaviour could be a way to increase social acceptance and to fit into a group. Students from both years were found to be goal orientated with poor study skills appearing to motivate dishonest behaviour.