Medication errors in hospitalised patients. / Legemiddelavvik hos pasienter innlagt i sykehus.

BACKGROUND: Errors in the use and administration of medicinal drugs are not uncommon. There is little up-to-date information available on medication errors in Norwegian hospitals. MATERIAL AND METHOD: It is compulsory to report all adverse events internally at St Olav's Hospital via an electronic form. For the three-year period 2015-2017 we have reviewed all medication errors in the database where the reports are stored and compared them with figures from a similar study conducted in the period 2002-2006. RESULTS: Altogether 1604 medication errors were registered, distributed among 1587 reports. Dosing errors were most common (n=1070; 67 %), followed by administration of another drug than prescribed (n=175; 11 %). Most errors were of an insignificant or low degree of severity. There was a preponderance of reporting among the youngest and the oldest patients. 79 % of the errors were reported by nurses. Inattention/forgetfulness (15 %), stress/high workload (12 %), sloppy documentation in drug charts (10 %) and erroneous/unclear prescribing (10 %) were reported as the most frequent causes. INTERPRETATION: The number of reports of medication errors is increasing, but the extent of underreporting is uncertain. The types of errors and their distribution are similar to previous studies. The underlying causes are also well known; the challenge is to prevent these situations from arising.

Safety with use of long-acting ß2-selective agonists for asthma. / Sikkerhet ved bruk av langtidsvirkende ß2-agonister ved astma.

BACKGROUND: Since their introduction more than 50 years ago, use of ß-agonists for inhalation has been associated with increased mortality. Since the turn of the century, particular concern has been voiced regarding long-acting ß2-selective agonists. Our purpose was to investigate the evidence from recently published randomised trials of possible increased risks of death and serious adverse events related to exposure to these drugs. MATERIAL AND METHOD: A PubMed search identified ten clinical trials which fulfilled predefined inclusion criteria. RESULTS: The ten trials encompassed 66 664 patients. A total of 16 asthma-related deaths after exposure to long-acting ß2-selective agonists were recorded among 33 043 actively treated patients, whereas four such deaths were recorded among the 33 621 patients in the control groups. A single, large, pragmatic trial accounts for a majority of these fatalities. INTERPRETATION: Exposure to long-acting ß2-selective agonists is associated with a small increase in mortality. Whether concomitant use of inhalation steroids fully reverses this effect is not clear.

Overgangen fra digitoksin til digoksin i årene 2011­13.

BACKGROUND: The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to follow individual patients during the switch. MATERIAL AND METHOD: Serum concentrations of digitoxin and digoxin, measured at the Department of Clinical Pharmacology at St Olavs University Hospital in the period 1 January 2011-31 December 2013 were reviewed. Patients who had switched from digitoxin to digoxin and whose serum concentrations of both drugs had been measured during this period were included. RESULTS: A total of 304 patients, 1686 samples and 1858 serum concentration analyses were included in the study. Therapeutic serum concentrations were measured in 171 patients (56.3 %) before the switch and 176 (57.9 %) after this had taken place. Altogether 108 patients (35.5 %) had therapeutic concentrations both before and after the change. For 58.9 % of the patients, the change resulted in a reduction in serum concentration of digitalis, calculated as digoxin equivalents. The proportion of patients with assumed supratherapeutic concentrations fell from 43.1 % to 33.9 %; however, the proportion of patients with toxic serum concentrations rose from 0.3 % to 3.0 %. INTERPRETATION: Although the switch led to a reduction in dose and serum concentration for many, a significant number of patients may have been put in harm's way.

The antipsychotic agent quetiapine is increasingly not used as such: dispensed prescriptions in Norway 2004-2015.

PURPOSE: The antipsychotic agent quetiapine was introduced in Norway in 2003. We have assessed changes in dispensed prescriptions, including dosing, of quetiapine in Norway from 2004 to 2015. METHODS: Data on the sales of antipsychotics and antidepressants were drawn from the Norwegian Prescription Database. A total of 47,474 outpatients filled 195,622 prescriptions of quetiapine. Reimbursement codes, use of antipsychotics or antidepressants 12 months prior to the first prescription of quetiapine and estimated mean volume used measured as defined daily doses (DDDs) per day were used as proxies for diagnoses. We conducted a regression analysis with DDD per day as a function of possible explanatory variables. RESULTS: The number of users filling at least two prescriptions of quetiapine per year increased from 584 in 2004 to 8506 in 2015 and the mean dose declined from 1.58 DDD per day (SD 8.00) to 0.48 DDD per day (SD 2.27). The latter is much lower than recommended for treatment of psychoses. In 2015, 60.1% of the 8506 quetiapine users did not seek reimbursement for the treatment of a major psychiatric disorder and only 2.6% of the patients were prescribed 1 DDD or more per day and reimbursed in accordance with the drug's primary indication, psychosis. A reported diagnosis of psychosis was not associated with higher quetiapine doses. CONCLUSIONS: In 2015, the pattern of quetiapine dispensing in Norway most likely reflects predominant off-label use. This is unsettling considering poorly documented effects in non-psychotic disorders, profound side effects, significant toxicity and growing concern regarding abuse.

[Cardiovascular safety of non-steroidal anti-inflammatory drugs]. / Hjerte, smerte - kardiovaskulær sikkerhet og ikke-steroide antiinflammatoriske midler.

BACKGROUND: The selective cyclooxygenase (COX)-2 inhibitor rofecoxib was withdrawn from the market in 2004 due to cardiovascular toxicity. We have evaluated data on adverse cardiovascular effects caused by COX-2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) since 2004. MATERIAL AND METHOD: Searches in PubMed (2004-2014) identified 243 relevant articles. Following a selection process, 63 articles were reviewed and evaluated in light of Norwegian practice. RESULTS: The results from the studies reviewed are heterogenous. A majority of data indicate that all the selective COX-2 inhibitors, diclofenac and high-dose ibuprofen cause adverse cardiovascular effects to a problematic extent, whereas naproxen consistently exhibits low or no risk. For most NSAIDs high dosage is related to increased risk, and the increase in risk appears to be present from the start of treatment. The effects of length of treatment and predisposition for cardiovascular disease are less clear. INTERPRETATION: Adverse cardiovascular effects is as a group effect that applies to all the NSAIDs studied, except for naproxen and low-dose ibuprofen. The traditional classification of NSAIDs as COX-2 selective and non-selective drugs is unsuited for risk stratification. The current pattern of consumption of NSAIDs in the population does not correspond to our knowledge of the increased risk to which patients are exposed.

[Patient reporting of adverse drug reactions in Norway 2010-13]. / Melding av legemiddelbivirkninger fra pasienter 2010-13.

BACKGROUND: Since 1 March 2010, patients in Norway have had the opportunity to report adverse reactions to The Norwegian Medicines Agency. The purpose of this study was to review these reports. MATERIAL AND METHOD: The content of adverse reaction reports received from patients in the period from 1 March 2010 to 31 December 2013 was classified based on age, gender, suspected drug and suspected adverse reactions. The patient reports were compared to the adverse reaction reports received from health care professionals in the same period. RESULTS: A total of 755 reports from patients and 9629 reports from health care professionals were received during the period in question. The 20-39-year age group was most frequently represented in the patient reports. In the reports from health care professionals, the main age group was 0-9 years, followed by the 60-69-year age group. The drug group most often mentioned in the patient reports was drugs acting on the nervous system, and above all psychotropic drugs and analgesics, while vaccines dominated in the reports from health care professionals. Adverse mental and neurological reactions were most frequently reported by patients, while general symptoms and local reactions were most common in the reports from health care professionals. A total of 74 different adverse reactions were reported only by patients and not by the health care professionals. INTERPRETATION: Adverse drug reaction reports from patients are different from reports by health care professionals. Our findings indicate that the system with patient reporting functions as a supplement to reporting from health care professionals.

[The polypill as cardiovascular prophylactic: clinical trials]. / Polypillen som kardiovaskulær profylakse--kliniske studier.

BACKGROUND: Cardiovascular disease dominates globally as the most common cause of death. This challenge may be countered by employing a combination pill (the «polypill¼) for prophylaxis by everybody above a certain age. The polypill normally contains two to three low-dose antihypertensives, a statin and aspirin. Clinical trials with the polypill are reviewed. METHOD: The databases PubMed and ClinicalTrials.gov were accessed for published, ongoing and planned randomised clinical trials with a polypill, and studies available per June 2013 were identified and evaluated. RESULTS: Six randomised clinical trials with different variations of a polypill have been published. In these, the polypill has been compared either with placebo (n = 3) or other cardiovascularly active pharmacotherapeutic strategies (n = 3). So far, no data on hard endpoints such as morbidity and mortality are available. On the basis of reductions in blood pressure and cholesterol levels, estimated risk reductions for ischemic heart disease and stroke were in the 33-72% and 21-64% ranges, respectively. INTERPRETATION: Additional studies of longer duration and with larger numbers of patients are required to assess the polypill's proposed effects on cardiovascular morbidity and mortality, as well as safety issues.

[Drug-drug interactions in nursing home patients]. / Legemiddelinteraksjoner hos pasienter i sykehjem.

BACKGROUND: Patients in nursing homes are often treated with many drugs concurrently (polypharmacy), which increases the risk of drug-drug interactions. The purpose of this study was to assess the incidence of such interactions in nursing home patients. MATERIAL AND METHOD: The study was based on medication lists collected from all nursing home patients in Trondheim Municipality in the course of one day in 2010. Data from the medication lists was linked to the Norwegian interaction database, Druid. RESULTS: The study included 1241 nursing home patients. Patients used an average of 9.8 drugs regularly or as needed, with a variation of from 0 to 30. In all, 15 patients (1.2%) used drug combinations that are classified in Druid as «should not be combined¼, while 592 (47.7%) used combinations classified as «take precautions¼. There was a clear relationship between the number of drugs prescribed and the risk of interactions. The three most common drug combinations in the group «should not be combined¼ were warfarin and non-steroidal anti-inflammatory drugs, clopidogrel and proton pump inhibitors, and anti-Parkinson medication and dopamine antagonists. CONCLUSION: The incidence of serious drug-drug interactions among nursing home patients in Trondheim Municipality is low. Polypharmacy is widespread, and the incidence of drug interactions where precautions should be taken is high. As nursing home patients are a vulnerable group with respect to drug interactions, the risk of interactions should be carefully considered when treatment with a new drug is started.

[Written pharmaceutical advertising--still unreliable?]. / Skriftlig legemiddelreklame--fremdeles ikke til å stole på?

BACKGROUND: Marketing by the pharmaceutical industry affects doctors' prescribing habits. MATERIAL AND METHOD: All pharmaceutical advertising received by nine doctors in two GP offices over a period of three months was collected. The advertising material was sorted by compound. For each compound, the advert with the highest number of references was selected. The cited references were obtained, and the claims in the adverts were assessed in terms of their consistency with the source data based on the provisions in the Norwegian regulations on pharmaceuticals. The references were also assessed with regard to the incidence of conflicts of interest among authors. RESULTS: The doctors received a total of 270 shipments of advertising for 46 different compounds. Altogether 95% of the 173 references cited in the 46 selected adverts could be obtained. The adverts contained a total of 156 claims. Of these, 56% were assessed as correct when compared to the source data and as having clinical relevance. Altogether 75% of the journal articles reported relevant conflicts of interest for the authors. INTERPRETATION: About half the claims in the adverts were found to be correct and clinically relevant. These results concur with those from a methodologically identical study based on advertising material collected in 2004. The cited literature was of varying quality and often funded by the pharmaceutical companies. The findings indicate that the target group should be sceptical of this type of marketing.

Retrospective screening of new psychoactive substances (NPS) in post mortem samples from 2014 to 2021.

Systematic retrospective processing of previously analysed biological samples has been proven to be a valuable tool in the search for new drugs (e.g. new psychoactive substances (NPS)) and for quality assessment in clinical and forensic toxicology. In a previous study, we developed a strategy for retrospective data-analysis using a personalized library of synthetic cannabinoids, designer benzodiazepines and synthetic opioids obtained from the crowdsourced database HighResNPS (https://highresnps.com). In this study, the same strategy was employed for the compounds within the groups of NPS that were not previously included such as synthetic cathinones, phenethylamines, aminoindanes, arylalkylamines, piperazine derivates, piperidines, pyrrolidines, indolalkylamines and arylcyclohexylamines. Synthetic opioids and designer benzodiazepines, which were not part of the previous study, were also included. To enhance the effectiveness of the retrospective analysis, a predicted retention time was included for all entries. Data files from the analysis of 2186 forensic post mortem samples with an Agilent Technologies 6540 ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in the laboratory from January 2014 to December 2021 were retrospectively processed with the up-to-date library. Tentative findings were classified in two groups: The findings where MS/MS data was acquired for library match (category 1) and the less certain findings where such data lacked (category 2). Five compounds of category 1 (three synthetic cathinones and two indolalkylamines) were identified in 12 samples. Only one of the findings, 4-MEAPP (4-methyl-α-ethylaminopentiophenone), was deemed plausible after reviewing case information. As many as 501 presumably positive category 2 findings were detected. Using the predicted retention time as an additional criterion the number was significantly reduced but still too high for a manual review. This work has demonstrated that the strategy developed in the previous study can be applied to other NPS groups. However, it is important to note the limitations such a method may have in detecting compounds at very low concentrations.