Fentanyl patches: Use and Misuse.

Transdermal fentanyl is a well-used and highly effective form of opioid analgesia for patients suffering with severe chronic pain. It is also an opioid that is widely abused. Acute clinicians need to be aware of the methods by which fentanyl patches may be used both therapeutically and illicitly as well as the impact this can have in managing a patient's period of intoxication.

The medico-legal significance of pharmacokinetic interactions with ethanol.

In the UK, the maximal permitted ethanol concentration for driving is 80 mg ethanol/100 mL blood, 35 µg ethanol/100 mL breath or 107 mg ethanol/100 mL urine. Drivers exceeding the prescribed limit face severe penalties, which they are often anxious to avoid, either by acquittal or by putting forward 'special reasons' why they should not be disqualified from driving. One frequently explored defence is that the accused was taking prescribed medication. Defence solicitors often ask the question whether the prescribed medication could have caused significantly altered blood ethanol concentrations. This paper reviews the impact of various medications and how they can influence the blood ethanol concentration. Although many drugs can interact with ethanol at a pharmacodynamic level, causing increased impairment, relatively few drugs interact with ethanol pharmacokinetically leading to significantly altered blood ethanol concentrations.

A patient's perspective: the impact of adverse drug reactions on patients and their views on reporting.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions to prescribed medication are relatively common events. However, the impact such reactions have on patients and their attitude to reporting such events have only been poorly explored. Previous studies relying on self-reporting patients indicate that altruism is an important factor. In the United Kingdom, patient reporting started in 2005; though, numbers of serious reports remain low. METHOD: A purposive sample of fifteen patients who had been admitted to an inner city hospital with an adverse drug reaction were interviewed using a semi-structured questionnaire. Patients were asked to relate in their own words their experience of an adverse drug reaction. Patient's reactions to the information leaflet, adherence to treatment and use of other sources of information on medication were assessed. Interviews were recorded, and a thematic analysis of patients' responses was performed. RESULTS AND DISCUSSION: Analysis of the patient interviews demonstrated the reality of being admitted to hospital is often a frightening process with a significant emotional cost. Anger, isolation, resentment and blame were common factors, particularly when medicines had been prescribed for acute conditions. For patients with chronic conditions, a more phlegmatic approach was seen especially with conditions with a strong support networks. Patients felt that communication and information should have been more readily available from the health care professional who prescribed the medication, although few had read the patient information leaflet. Only a minority of patients linked the medication they had taken to the adverse event, although some had received false reassurance that the drug was not related to their illness creating additional barriers. In contrast to previous studies, many patients felt that adverse drug reporting was not their concern, particularly as they obtained little direct benefit from it. The majority of patients were unaware of the Yellow Card Scheme in the UK for patient reporting. Even when explained, the scheme was felt too cold and impersonal and not a patient's 'job'. WHAT IS NEW AND CONCLUSION: Patients having a severe adverse drug reaction following an acute illness felt negative emotions towards their health care provider. Those with a chronic condition rationalized the event and coped better with its impact. Neither group felt that reporting the adverse reaction was their responsibility. Encouraging patients to report remains important but expecting patients to report solely for altruistic purposes may be unrealistic.

Therapeutic misadventure.

Therapeutic misadventure can be defined as an injury or an adverse event caused by medical management rather than by an underlying disease. Within the National Health Service there were over 86,000 reported adverse incidents in 2007. In the USA medication errors have been rated as the fourth highest cause of death. Unfortunately one of the greatest contributors to iatrogenic injury is human error. The potential types of misadventure are infinite. Medication errors are a major part of this, being responsible for over 70% of cases that cause serious harm. However, many medication errors caused by slips, lapses, technical errors and mistakes are preventable; intentional violations of safe operating procedures are not. While medication errors were tolerated by society in the past, the readiness to institute criminal proceedings against health-care professionals has increased greatly in the UK over the last decade. The medication process consists of writing prescriptions, dispensing the product, administering it and monitoring its effects. Prescription errors arise owing to incomplete information, lack of appropriate labelling, environmental factors and human blunders. Even with a perfect prescription the right medication must be dispensed and appropriately labelled. Dispensing errors are not uncommon and may be compounded by non-clinical considerations. Administration of a drug by injection is one of the most dangerous aspects of the medication process, especially in inexperienced hands. The final component of medication supply is monitoring the effect of the medication. With short courses of medication such monitoring is easy, but with long-term medication, particularly with potent drugs where the margin between efficacy and toxicity is small, active procedures may be required to ensure toxicity does not ensue. Despite the endeavour of health-care professions to stick to the rule of 'first, do no harm', in reality this is difficult to achieve all of the time. When errors occur the natural thoughts of wanting to blame an individual at the sharp end (active error) should be tempered. Identifying and correcting system (latent) errors will, in the end, provide a safer health-care system.

Ethnicity and other risk factors for acute lower limb cellulitis: a U.K.-based prospective case-control study.

BACKGROUND: Acute lower limb cellulitis is a common yet potentially serious condition. Previous studies have identified risk factors in the non-U.K. population. Ethnicity has been postulated as a possible risk factor but has not previously been investigated. OBJECTIVES: To identify risk factors for acute lower limb cellulitis in the U.K. population. METHODS: One hundred and fifty consecutive patients with cellulitis requiring hospital admission and 300 controls were recruited to this prospective case-control study. Controls were matched for age and sex. RESULTS: Strongly predictive risk factors for acute lower limb cellulitis in the U.K. include being of white ethnicity and preceding episodes of injury to the affected leg. No systemic illnesses were identified as increasing an individual's risk of presenting with cellulitis. CONCLUSIONS: This study has identified that patients of white ethnicity are at higher risk of developing acute lower limb cellulitis compared with other ethnic groups. The importance of local risk factors has also been shown in the U.K. population.

Changes in the chemical form of selenium observed during the manufacture of a selenium-enriched sourdough bread for use in a human nutrition study.

High-performance liquid chromatography interfaced with inductively coupled plasma mass spectrometry, and hydride generation-inductively coupled plasma mass spectrometry were used, respectively, to investigate changes in both the chemical form and the concentration of selenium during its bio-incorporation and bio-accumulation into rye seedlings. A 60-fold increase in the total level of selenium in the seedlings ('control' biomass = 0.99 mg kg(-1), 'enriched' biomass = 55.27 mg kg(-1)) was accompanied by a change from selenite to several organo-selenium forms, with more than 40% being present as selenomethionine. The seedling biomass was dried, ground and used as an ingredient in the production of a fermented sourdough bread (popular in Poland and many Eastern European countries). The selenium in the resulting bread was also characterized in terms of its speciation, as well as its total selenium content ('control' bread = 0.06 mg kg(-1), 'enriched' bread = 3.56 mg kg(-1)). The breads were then fed to 24 volunteers as part of a human intervention study designed to establish the efficacy of this mode of selenium supplementation. The human study data subsequently showed the bread was a good source of dietary selenium.

Deep vein thrombosis assessment clinic: Evaluation of a new working practice.

Suspected deep vein thrombosis (DVT) is a common reason for medical referral to hospital. We evaluated our new approach to assessment of DVT using combined automated strain gauge plethysmography and pretest probability score in comparison with venous ultrasonography in 100 consecutive patients with suspected DVT referred to the nurse-led clinic. The combined plethysmography and pretest probability score produced a negative predictive value of 99%, positive predictive value 53%, sensitivity 94% and specificity 83% for detection of a DVT. We conclude that our new working practice for DVT assessment is both safe and cost effective and can lead to a reduction in venous ultrasonography of approximately 70%.

BANs to rINNS.

Medical errors are increasingly being highlighted as an unnecessary cause of morbidity and mortality. Such situations are increasingly likely to occur if each country has its own improved name for each individual drug, particularly as healthcare staff are becoming increasingly mobile across the world. Standardization of drug names will help reduce the risk of such errors. However because of the change between BANs and rINNS there is potential for short-term problems. Healthcare staff need to be aware of such problems to try and minimize the damage they could potentially cause. In the longer term these name changes will hopefully prevent errors from occurring.

Testing the practical aspects of therapeutics by objective structured clinical examination.

Medical students need to have a sound theoretical knowledge of pharmacology and a training in the practical aspects of therapeutics in order to prescribe effectively, safely and rationally when they qualify. Students have traditionally sat written exams and the practical aspects have been largely ignored. At the University of Birmingham we set up an objective structured clinical examination (OSCE) style examination to test the practical aspects of therapeutics. Over the last 2 years, 434 students have been examined in this way to determine competency in various clinical skills including, for example prescription writing, the drawing up and giving of injections, setting up nebulizers, and patient counselling about drug effects. Over that time we found the therapeutics OSCE to be feasible and useful. It has demonstrated serious practical deficiencies that were not apparent from written examinations in some students' ability to prescribe and administer drugs. Since its introduction, performance in the OSCE has improved. Whether this will result in safer and more effective prescribing in the preregistration house officer year has not been formally evaluated but it appears that they approach this aspect of patient care with greater confidence than graduates from other schools.

Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes.

OBJECTIVE: To measure the bioavailability of selenium from cooked and raw fish in humans by estimating and comparing apparent absorption and retention of selenium in biosynthetically labelled fish with labelled selenate and biosynthetically labelled selenium in brewers yeast. DESIGN: The intervention study was a parallel, randomised, reference substance controlled design carried out at two different centres in Europe. SETTING: The human study was carried out at the Institute of Food Research, Norwich, UK and at TNO Nutrition and Food Research, Zeist, The Netherlands. SUBJECTS: In all, 35 male volunteers aged 18-50 y were recruited; 17 subjects were studied in Norwich (UK) and 18 in Zeist (Netherlands). All of the recruited subjects completed the study. INTERVENTIONS: Biosynthetically labelled trout fish (processed by two different methods), biosynthetically labelled brewers yeast and isotopically labelled selenate were used to estimate selenium apparent absorption and retention by quantitative analysis of stable isotope labels recovered in faeces and urine. Subjects consumed the labelled foods in four meals over two consecutive days and absorption was measured by the luminal disappearance method over 10 days. Urinary clearance of isotopic labels was measured over 7 days to enable retention to be calculated. RESULTS: Apparent absorption of selenium from fish was similar to selenate and there was no difference between the two processing methods used. However, retention of fish selenium was significantly higher than selenate (P<0.001). Apparent absorption and retention of yeast selenium was significantly different (P<0.001) from both fish selenium and selenate. CONCLUSION: Fish selenium is a highly bioavailable source of dietary selenium. Cooking did not affect selenium apparent absorption or retention from fish. Selenium from yeast is less bioavailable.

Quinine intoxications reported to the Scottish Poisons Information Bureau 1997-2002: a continuing problem.

Quinine is widely prescribed in the UK for night cramps. Its potential toxicity in overdose is well known. We have reviewed the Scottish experience of enquiries regarding quinine overdose to the poisons information service responsible for Scotland over a 6-year period. Between 1997 and 2002 there were 96 reports of suspected quinine toxicity from Scotland (population 5.2 million), 19 of which were in children. The largest quantities of drug ingested were in patients between the ages of 11 and 30. In comparison with older studies the pattern of quinine poisoning does not appear to have changed in the UK over 20 years, despite recognition that it is a toxic agent in overdose, and particularly in children.

Paracetamol poisoning--impact of pack size restrictions.

BACKGROUND: Pack sizes of paracetamol available to the public were reduced by legislation in 1998. OBJECTIVE: To study the effect of the legislation on paracetamol poisoning related admissions to an accident and emergency department and to a tertiary referral liver unit. METHOD: Data were obtained from the University Hospitals, Birmingham, UK (UHB) Trust Information Service and the Queen Elizabeth Hospital liver unit records on (a) the number of patients admitted to hospital because of paracetamol overdose and (b) the number of patients admitted to the liver unit with parcetamol-induced hepatotoxicity. RESULTS: Prior to legislation, an average of 360 people a year were admitted to UHB. However, following the change in legislation the number of admissions has fallen to an average of 250 people per year. This represents a reduction of 31%. Prior to legislation, an average of 76 people per year were admitted to the liver unit. Post-legislation this number has dropped to an average of 38 per year representing a reduction of 50%. CONCLUSION: Legislation restricting paracetamol pack-size reduced the incidence and severity of poisoning.

Alternative venlafaxine kinetics in overdose.

UNLABELLED: The pharmacokinetics of venlafaxine in therapeutic doses is well established. It is metabolized by the cytochrome P450 enzymes including CYP2D6. The toxicokinetics in overdose is less well known. CASE REPORT: A 33-year-old Caucasian female who ingested 3.0 g venlafaxine, and 210 mg zolpidem. The patient remained symptomatic for the following 24 h. Plasma pharmacokinetic analysis demonstrated a prolonged elimination half-life of venlafaxine, estimated to be 15.3 h. We postulate that the patient was a slow metabolizer of substrates for CYP2D6, an enzyme known to exhibit polymorphism.

Random and systematic medication errors in routine clinical practice: a multicentre study of infusions, using acetylcysteine as an example.

AIMS: The nature and incidence of errors in prescribing and giving medicines have previously been estimated by trained observers, or by retrospective analysis of incidents in which patients have come to harm. We have examined prospectively in routine clinical practice the concentrations of intravenous infusions of a drug (acetylcysteine) which is given according to a complicated dosing schedule. METHODS: We prospectively collected samples before and, where possible, after the infusion of acetylcysteine in 66 anonymous patients requiring treatment for acetaminophen (paracetamol) overdose in four centres in the United Kingdom. We measured the concentration in each infusion bag, and deduced from the weight of the patient the percentage of the anticipated dose that had actually been given. RESULTS: The experimentally determined dose was within 10% of the anticipated dose in 68 of 184 individual bags (37%), and within 20% of the anticipated dose in 112 bags (61%). Doses in 17 bags were more than 50% from the anticipated doses. In three patients, values in all three bags appeared to be systematically wrong by 50% or more; in a further seven cases, individual bags differed by 50% or more from the anticipated value. The median difference between pre- and post-infusion samples was 0% [interquartile range -5.2% to +14.6%], but 9% showed a disparity of greater than +/- 50%. CONCLUSIONS: Our data suggest that there is large random variation in administered dosage of intravenous infusions. Systematic calculation errors occur in about 5% [95% confidence interval 2, 8%] of cases, and major errors in drawing up in a further 3% [1, 7%], with inadequate mixing in 9% [4, 14%]. While we have no evidence that patients were adversely affected, and while the regime of administration of the drug studied (acetylcysteine) is complicated, these data suggest that the delivered dose often deviates from the intended dose, and that methods of quality control are needed.