Stig Ejdrup Andersen

Insufficient communication about medication use at the interface between hospital and primary care

Background: Lack of updated and uniform medication lists poses a problem for the continuity in patient care. The aim of this study was to estimate whether hospitals succeed in making accurate medication lists congruent with patients’ actual medication use. Subsequently, the authors evaluated where errors were introduced and the possible implications of incongruent medication lists. Methods: Patients were visited within one week after discharge from surgical or medical department and interviewed about their use of prescription-only medication (POM). Stored drugs were inspected. Medication lists in hospital files and discharge letters were compared with the list obtained during the interview. The frequency of incorrect medication use and the potential consequences were estimated. Results: A total of 83 surgical and 117 medical patients were included (n = 200), 139 patients (70%) were women. Median age was 75 years. Six patients stored no POM, 194 patients stored 1189 POM. Among the 955 currently-used POM, 749 POM (78%) were registered at some point during hospitalisation but only 444 (46%) were registered in discharge letters. 66 POM users had no medication list in their discharge letter. Local treatments (skin, eyes, airways) were registered less frequently than drugs administered orally. In total, 179 of the currently-used POM (19%) were not mentioned anywhere in hospital files, probably because of insufficient medication lists made at admission, and the prescribed regimen was unclear. At least 63 POM (7% of currently-used POM) were used in disagreement with the prescribed regimen. Discussion: Approximately one fifth of used POM is unknown to the hospital and only half of used POM registered in discharge letters. Insufficient medication lists hamper clarifying whether or not patients use medication according to prescription. In order to prevent medication errors a systematic follow-up after discharge focusing on making an updated medication list might be needed.

Does Pharmacogenetic Testing for CYP450 2D6 and 2C19 Among Patients with Diagnoses within the Schizophrenic Spectrum Reduce Treatment Costs

The effect of pharmacogenetic testing for CYP450 2D6 and 2C19 on treatment costs have not yet been documented. This study used Danish patient registers to calculate healthcare costs of treating patients with diagnoses within the schizophrenic spectrum for 1 year with or without pharmacogenetic testing for polymorphisms in the genes for the CYP2D6 and CYP2C19 enzymes. In a randomized, controlled trial, stratified with respect to metabolizer genotype, 104 patients were assigned to treatment based on pharmacogenetic testing and 103 patients to treatment as usual. Random exclusion of extensive and intermediate metabolizers was used to increase the frequency of extreme metabolizers (poor metabolizers and ultrarapid metabolizers for CYP2D6) to 20% in both groups. Cost differences were analysed at several levels including (i) overall healthcare expenditure, (ii) psychiatric hospital cost (iii) nonpsychiatric hospital cost, (iv) primary care spending and (v) pharmaceuticals. Statistically significant differences in costs of psychiatric care dependent on metabolizer status were found between intervention groups. Pharmacogenetic testing significantly reduced costs among the extreme metabolizers (poor metabolizers and ultrarapid metabolizers) to 28%. Use of primary care services and pharmaceuticals was also affected by the intervention.This study confirms earlier findings that extreme metabolizers (poor and ultrarapid metabolizers) incur higher costs than similar patients with a normal metabolizer genotype. However, this study shows that these excess costs can be reduced by pharmacogenetic testing. Pharmacogenetic testing for CYP2D6 and CYP2C19 could thus be considered as a means of curtailing high psychiatric treatment costs among extreme metabolizers.

The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these patients. A total of 104 APAP-poisoned patients were genotyped for deletion polymorphisms in the GSTT1 and GSTM1 genes and for the GSTP1 Ile105Val polymorphism. We found a borderline association (p = 0.05) between the GSTT1 homozygous deletion genotype and high trough PT (a marker of prognosis in APAP poisoning) compared to carrying two functioning copies of the gene. No significant association was found between any of the GSTM1 and GSTP1 genotypes and PT. The frequency of GSTP1 Val/Val genotypes was significantly lower in the patients than in the background population (p = 0.047). The results suggest that the GSTT1 homozygous deletion genotype may be associated with a better prognosis after APAP poisoning and that carriers of the GSTP1 homozygous variant genotype may have a decreased risk of being APAP poisoned.

Adverse effects associated with high-dose olanzapine therapy in patients admitted to inpatient psychiatric care

Context. In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units. Methods. The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population. Results. The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death. Conclusion. Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

General Practitioners' and Hospital Physicians' Preference for Morphine or Oxycodone as First‐Time Choice for a Strong Opioid: A National Register–Based Study

The aim of this study was to characterize first‐time oxycodone and morphine prescriptions in outpatients by type of prescriber and naivety in regard to strong opioids. All prescriptions for morphine and oxycodone in Denmark reported to the National Register of Medicinal Product Statistics in 2010 were analysed. If a patient had not had a prescription filled for the same drug within the last 2 years, the prescription was defined as a first‐time prescription. Patients who had not received a prescription for strong opioids for 6 months prior to the date of redemption were classified as strong opioid naive. The odds ratio (OR) was calculated to investigate whether general practitioners (GPs) and hospital physicians had similar preferences for oxycodone over morphine for strong opioid–naive patients. We included 69,110 first‐time prescriptions, of which 59,316 (86%) were for strong opioid–naive patients. Opioid‐naive patients received 79% of the first‐time prescriptions for morphine and 91% of the prescriptions for oxycodone. Hospital physicians had a greater preference for oxycodone over morphine than GPs (OR 1.34, 95% CI 1.29–1.39). However, GPs were responsible for approximately 61% of all first‐time prescriptions for both oxycodone and morphine for strong opioid–naive patients. In conclusion, oxycodone is to a great extent prescribed as the first‐choice strong opioid, and both GPs and hospital physicians seem to contribute to this prescribing pattern of strong opioids to outpatients.

The quality and quantity of patients' own drugs brought to hospital during admission

Objectives Patients’ own drugs (PODs) are the medicines that patients have obtained in the community setting and bring to hospital. Little is known about the frequency with which patients bring PODs when admitted to hospital and the quality of these drugs has not been well investigated. The purpose of this study was to evaluate the quantity and quality of the PODs brought to hospital during admission. Methods Clinical pharmacists in four wards at three different hospitals evaluated the quantity and quality of PODs. The quantity of PODs relates to the number of patients who brought one or more of their medicines to hospital and the total number of PODs. The quality of PODs was evaluated by assessing the appearance, container, labelling, identification of contents, storage conditions and expiration, and thereby the usability of the POD. Results From March 2010 to July 2011, 4600 drugs from 529 patients were assessed. In total, 59% of patients took PODs to hospital and 43% (n=1985) of drugs from patients’ medication histories were brought to the hospital. The majority of PODs were usable (58.6%, n=1164) but most were unnecessary (52.3%, n=1039) because substitution was possible. In total, 92.5% (n=1836) of all PODs were not used during admission, although 33.5% (n=615) of these added information to the patients’ medication history. Conclusions More than half of patients brought PODs to hospital which gave the advantage of providing medication history. The majority of PODs were suitable for use in hospital. Only 7.5% of all PODs were actually used because substitution to generic or equivalent drugs from the hospitals formulary was preferred.

The prescribing pattern of a new antipsychotic: a descriptive study of aripiprazole for psychiatric in-patients.

In June 2004, aripiprazole was marketed as a second-generation antipsychotic with an entire new mechanism of action. The objective of this descriptive study is to examine the day-to-day prescriptions of aripiprazole to an unselected population of psychiatric in-patients. From 1 February to 1 May 2006, present and former in-patients treated with aripiprazole were identified. Prescriptions of aripiprazole and psychoactive comedication were collected retrospectively from the patient records. Seventy-one patients, mainly schizophrenic, received aripiprazole 2.5 to 55 mg/day for median 350 days. The median average exposure was 18.9 mg/day (range 2.5-45 mg/day) and exceeded 15 and 30 mg/day in 63% and 4.2% of the patients, respectively. Generally, aripiprazole was either added to the existing antipsychotic treatment or replaced other antipsychotics; only 17% of the patients were treatment-naïve. In 25% aripiprazole, monotherapy was commenced whereas aripiprazole-antipsychotic combinations were initially prescribed in 75%. Overall, 85% of the patients received periods of antipsychotic polypharmacy and aripiprazole was combined with 17 different antipsychotics. Each patient received median three (range 0-8) psychoactive drugs parallel with aripiprazole. This study demonstrates reality in psychopharmacology and quote aripiprazole as example. In day-to-day practice, aripiprazole is used as part of highly individualized regimens comprising polypharmacy and excessive dosing. Although theoretically appropriate for some patients, this approach also implies conducting unblinded and uncontrolled mini-experiments. Sparse evidence supports this practice and effectiveness studies of aripiprazole that takes into account the true complexity of clinical prescribing are urgently needed.

Does the medication pattern reflect the CYP2D6 genotype in patients with diagnoses within the schizophrenic spectrum

Background Cytochrome P450 2D6 enzyme (CYP2D6) is an important metabolic pathway for many antipsychotics. Its genetic polymorphism causes pharmacokinetic variability that might lead to adverse drug reactions or treatment failure unless countered by appropriate dose adjustments or shift to CYP2D6-independent antipsychotics. Purpose To investigate the clinical impact of CYP2D6 genotype in patients with a diagnosis within the schizophrenic spectrum using medication pattern as proxy for therapeutic and side effect. Methods The study was conducted in patients genotyped during an inpatient stay (N = 576). Continuous antipsychotic, adjuvant, and anticholinergic drug regimens were registered retrospectively in a cross-sectional manner before genotyping. Antipsychotics were divided into CYP2D6 dependent and independent, and dose equivalents were calculated as chlorpromazine equivalents (CPZEq). Results Poor metabolizers and ultrarapid metabolizers were treated with significantly higher median CPZEq doses (625.8; inter quartile range [IQR], 460.4–926.7; and 550; IQR, 199.8–1049) than extensive metabolizers (EMs) and intermediate metabolizers (IMs) (384; IQR, 150–698; and 446; IQR, 150–800) (P = 0.018). Logistic regression showed no association between anticholinergic treatment and CYP2D6 genotype or concomitant treatment with CYP2D6 inhibitors (P = 0.79 and P = 0.46, respectively). Conclusions Our results indicate that CYP2D6 genotype has no sufficient clinical impact that poor metabolizers and ultrarapid metabolizers are easily clinically identified with.

Drug dispensing errors in a ward stock system.

The aim of this study was to determine the frequency of drug dispensing errors in a traditional ward stock system operated by nurses and to investigate the effect of potential contributing factors. This was a descriptive study conducted in a teaching hospital from January 2005 to June 2007. In five wards, samples of dispensed solid drugs were collected prospectively and compared with the prescriptions. Data were evaluated using multivariable logistic regression. Overall, 2173 samples were collected, 95.5% of which were correctly dispensed (95% CI 94.5-96.2). In total, 124 errors in 6715 opportunities for error were identified; error rate of 1.85 errors per 100 opportunities for error (95% CI 1.54-2.20). Omission of a dose was the predominant type of error while vitamins and minerals, drugs for acid-related diseases and antipsychotic drugs were the drugs most frequently affected by errors. Multivariable analysis showed that surgical and psychiatric settings were more susceptible to involvement in dispensing errors and that polypharmacy was a risk factor. In this ward stock system, dispensing errors are relatively common, they depend on speciality and are associated with polypharmacy. These results indicate that strategies to reduce dispensing errors should address polypharmacy and focus on high-risk units. This should, however, be substantiated by a future trial.

Clinical Effects of a Pharmacist Intervention in Acute Wards - A Randomized Controlled Trial.

The purpose of the study was to investigate the clinical effect of a clinical pharmacist (CP) intervention upon admission to hospital on inpatient harm and to assess a potential educational bias. Over 16 months, 593 adult patients taking ≥4 medications daily were included from three Danish acute medicine wards. Patients were randomized to either the CP intervention or the usual care (prospective control). To assess a potential educational bias, a retrospective control group was formed by randomization. The CP intervention comprised medication history, medication reconciliation, medication review and entry of proposed prescriptions into the electronic prescribing system. The primary outcome of inpatient harm was identified using triggers from the Institute of Healthcare Improvement Global Trigger Tool. Harms were validated and rated for severity by two independent and blinded outcome panels. Secondary end‐points were harms per patient, length of hospital stay, readmissions and 1‐year mortality. Harm affected 11% of the patients in the intervention group compared to 17% in the combined control group, odds ratio (OR) 0.57 (CI 0.32–1.02, p = 0.06). The incidence of harm was similar in the intervention and prospective control groups, OR 0.80 (CI 0.40–1.59, p = 0.52) but occurred less frequently in the intervention than in the retrospective control group OR 0.46 (CI 0.25–0.85, p = 0.01). An educational bias from the intervention to the control group might have contributed to this negative outcome. In conclusion, the CP intervention at admission to hospital had no statistically significant effect on inpatient harm.