Self-perceived learning outcomes of virtual and in-person academic detailing among general practitioners in Norway.

Self-perceived learning outcomes of virtual academic detailing (AD) are poorly studied. We compared self-perceived learning outcomes of virtual and in-person AD among general practitioners (GPs). GPs from the Western region of Norway received a questionnaire before and after AD concerning rational pharmacotherapy of migraine in the autumn 2022. Five statements addressing specific knowledge and two statements addressing general knowledge and skills in pharmacotherapy of migraine were rated in both questionnaires. A 7-point Likert scale ranging from 1: Strongly disagree to 7: Strongly agree was applied to all the statements. Histograms that showed the difference in the mean composite scores before and after AD were used to compare learning outcomes of virtual and in-person AD. Positive self-perceived learning outcomes were observed among 80%-88% of the GPs. No significant differences between virtual and in-person AD were observed.

Can academic detailing reduce opioid prescriptions in chronic non-cancer pain?

BACKGROUND: One measure to support optimal opioid prescription is academic detailing (AD) with one-to-one visits by trained professionals (academic detailers) to general practitioners (GPs). OBJECTIVE: To investigate the usefulness of AD visits on GPs' opioid prescribing patterns in Norway, and academic detailers' experiences with AD visits to GPs on opioid prescription. METHODS: Design: A quantitative registry study on opioid prescriptions and a qualitative focus group interview study with academic detailers. PARTICIPANTS: For the registry study, municipalities where more than 75% of the GPs had received an AD visit were considered intervention municipalities, whereas in the non-intervention municipalities no GPs had received AD-visits. In the focus groups, academic detailers who had conducted three or more AD-visits were invited to participate. INTERVENTION: A campaign on opioid prescription with AD visits using a brochure with key messages based on the national guideline for treatment of chronic non-cancer pain and updated evidence on the potential benefits and risks of prescribing opioids. The AD visits in the campaign were planned for 20-25 min in a one-to-one setting in the GP's office. MAIN MEASURES: The Norwegian Prescription Database (NorPD) was utilized for registry data. Data on amount of drugs dispensed are recoded as Defined Daily Doses (DDDs). RESULTS: Compared to non-intervention, the intervention resulted in a decrease in the number of prevalent and incident users of opioids and incident users of reimbursed opioids for chronic non-cancer pain in municipalities in Central Norway. The results from the focus group interviews were categorized into the themes: "To get in position", "Adjusting messages", "What did the GPs struggle with, in relation to opioid prescription?" and "Did we reach the right recipients with the visits?". CONCLUSIONS: In Central Norway, the intervention resulted in a desired effect on number of opioid users. According to the academic detailers, the GPs' length of working experience and familiarity with the topic gave different presumptions for making use of the information presented in the AD-visits.

Cohort Description: Preventing an Opioid Epidemic in Norway - Focusing on Treatment of Chronic Pain (POINT) - A National Registry-Based Study.

Aim: The POINT project aims to provide evidence to optimise chronic pain management, prevent adverse consequences of opioids, and improve chronic pain patients' pain relief, functional capacity, and quality of life. We describe the outline of the project and its work packages. More specifically, we describe a cohort of persons with chronic pain and a cohort of long-term opioid users identified from a national registry linkage. Data Sources: The project utilises data from nationwide healthcare and population registers in Norway. Using the Norwegian Prescription Database, we identified a cohort of persons who have been dispensed drugs reimbursed for chronic pain and a cohort of persons who used opioids long term from 2010 to 2019. Data from the Norwegian Registry for Primary Health Care and the Norwegian Patient Registry (2008-2019), Cancer Registry (1990-2018) Cause of Death Registry (2010-2019) and demographic and socioeconomic registers from Statistics Norway (2010-2019) were linked to the cohorts. Study Population: There were 568,869 participants with chronic pain. Sixty-three percent of the cohort was women, and the mean age was 57.1 years. There were 336,712 long-term opioid users (58.6% women; 60.9 years). In chronic pain and long-term opioid user cohorts, the most frequent musculoskeletal diagnosis was back pain diagnosed in primary care (27.6% and 30.7%). Psychiatric diagnoses were also common. Main Variables: Upcoming studies will utilise psychiatric and somatic diagnoses from the patient registers, drug use from the prescription register, causes of death, demographics, and socioeconomic status (eg, education, income, workability, immigrant status) as exposures or outcomes. Conclusion and Future Plans: The two cohorts have numerous pain-related diagnoses, especially in the musculoskeletal system, and noticeably frequent somatic and psychiatric morbidity. The POINT project also includes later work packages that explore prescriber and patient perspectives around safe and effective treatment of chronic pain.

Randomised controlled trial showed long-term efficacy, immunogenicity and safety of varicella vaccines in Norwegian and Swedish children.

AIM: Several countries, such as Norway and Sweden, have not implemented universal varicella vaccination. We present data for Norway and Sweden that were generated by a paediatric multi-country Phase III study over a 10-year period. This assessed the efficacy, antibody persistence and safety of two varicella vaccines containing the same Oka strain. METHODS: This was an observer-blind, controlled trial conducted in 10 European countries. Children aged 12-22 months (n = 5803) were randomised 3:3:1 and vaccinated between 1 September 2005 and 10 May 2006. The two-dose group received two tetravalent measles-mumps-rubella-varicella vaccine doses. The one-dose group received one monovalent varicella vaccine dose after a measles-mumps-rubella vaccine dose. Control group participants received two measles-mumps-rubella vaccine doses. Main study outcomes were vaccine efficacy against confirmed varicella cases and incidence of adverse events. RESULTS: Vaccine efficacy in the two-dose group was ≥92.1% in both Norwegian and Swedish children compared to 72.3% in Norway and 58.0% in Sweden in the one-dose group. Incidences of adverse events and serious adverse events were similar in the Norwegian and Swedish study populations. CONCLUSION: Consistent with overall study results, high efficacy against varicella and acceptable safety profiles of the two varicella vaccines were observed in Norwegian and Swedish populations. These findings highlight the benefits of varicella vaccines, particularly when administered as a two-dose schedule.

Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVES: Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state. METHOD: A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model. FINDINGS: The mean steady-state serum concentration of metformin during pregnancy was 9.39 µmoL/L, whereas the post partum concentration was 12.36 µmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum. CONCLUSION: Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.

Academic detailing as a method of continuing medical education.

INTRODUCTION: Academic detailing is an interactive educational outreach to prescribers to present unbiased, non-commercial, evidence-based information, mostly about medications, with the goal of improving patient care. Academic detailing in Norway is an approach for providing continuing medical education to general practitioners (GPs). The basis of academic detailing is a one-to-one discussion between a trained health professional (the academic detailer) and the GP at the GP's workplace. METHOD: Our first campaign was named "Better use of non-steroidal anti-inflammatory drugs (NSAIDs)", which aim was to reduce the use of diclofenac due to the risk of serious cardiovascular adverse events. At the same time we advised the GPs to use naproxen as the drug of choice if an NSAID was needed. We did a one-to-one intervention in two cities, where a trained academic detailer met the GP during office hours. A total of 247 GPs were invited to participate and 213 visits (86%) were completed. This article reviews the theoretical framework underlying the method and describes the development and implementation of academic detailing to GPs in Norway. RESULTS: More than 90% the participating GPs considered academic detailing a suitable method for providing up-to-date evidence-based, manufacturer-independent information, and nearly all would most likely or probably welcome another visit. After the intervention there was a reduction of diclofenac prescribing of 16% and 18%, respectively, in the two cities. CONCLUSION: We consider that academic detailing is a suitable method to bring the best available evidence to the point at which care is delivered, to achieve the best for the patients. According to the Norwegian GPs' evaluation, it is a key supplement to other methods of continuing medical education. To have maximum impact, it is important that academic detailing is practiced according to the consensus that has evolved in the USA and Australia.

Peer academic detailing on use of antibiotics in acute respiratory tract infections. A controlled study in an urban Norwegian out-of-hours service.

OBJECTIVE: To analyse if peer academic detailing by experienced general practitioners (GPs) could be a useful way to change Medical Doctors, (MDs) prescription of antibiotics for acute respiratory tract infections (ARTIs) in out-of-hours service. METHOD: An educational Intervention study based on prescription data among MDs working in an out-of-hours service from June 2006 through October 2008. Specially trained GPs lectured a peer educational program (3 × 45 minutes) about use of antibiotics for ARTIs according to national recommendations. OUTCOME MEASURES: The type and frequency of antibiotics prescribed for different ARTIs before and after intervention comparing the intervention group with the control group. SUBJECTS: 22 MDs in the intervention group and 31 MDs in the control group. RESULTS: The intervention group showed an overall statistically significantly absolute increase in the use of penicillin V (Penicillin V) of 9.8% (95% CI: 2.3%-17.4% p < 0.05), and similarly an statistically significantly absolute decrease in the use of macrolides and lincosamides of 8.8% (95% CI: 2.6%-14.9.2% p < 0.05) for all diagnoses. For subgroups of ARTIs we found a significant increase in the use of Penicillin V for acute otitis media, sinusitis, pneumonia and upper ARTIs. There was no significant changes in total prescription rates in the two groups. 41% of all consultations with respiratory tract infections resulted in antibiotic prescription. CONCLUSIONS: Using trained GPs to give peer academic detailing to colleagues in combination with open discussion on prescription, showed a significant change in prescription of antibiotics towards national guidelines. Key points Phenoxymethylpenicillin is the first choice for the most of respiratory tract infections when indicated. Despite the guidelines for the choice of antibiotics in Norway, general practitioners' choice often differs from these. We showed that a session of three times 45 min of peer academic detailing changed significantly the choice of antibiotics towards the National Guidelines in an urban Norwegian out-of-hours service.

Sedative and hypnotic drugs--fatal and non-fatal reference blood concentrations.

In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden - where these drugs had been detected in femoral vein blood during 1992-2006 - were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases - where the cause of death was not intoxication and where incapacitation by drugs could be excluded - were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N=498), multiple substance intoxications (N=1555) and postmortem controls (N=1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug concentrations primarily to be used for improving interpretation of postmortem drug levels in obscure cases, but which also may assist in drug safety work and in pharmacovigilance efforts.

Therapeutic drug monitoring (TDM) repertoire in Norway.

BACKGROUND: In many clinical situations it is useful to measure drug levels in patient samples. The purpose of this survey is to obtain an overview of the therapeutic drug monitoring analyses offered by Norwegian laboratories. MATERIAL AND METHOD: At the end of 2011, the authors of this article phoned all the public and private hospitals in Norway, and located their laboratories. All clinical chemical and pharmacological laboratories were contacted and asked to state which drug analyses (including drugs-of-abuse and toxic alcohols, but excluding metabolites) they performed in blood/serum at the time in question. The overview thus obtained was updated and quality assured by means of further telephone contact with the laboratories in August 2012. RESULTS: Around 80 laboratories were contacted. In August 2012, 49 of them performed analyses of drugs in blood/serum. Altogether, these laboratories offered 151 different analyses. This article provides an overview of the analyses that were carried out, and where. INTERPRETATION: The overview of analyses provided here can be used as a tool in everyday practice. However, the user must be aware that the analytical repertoire of the laboratories is constantly changing. A web-based, dynamic version is currently being planned.

A puzzling case of increased serum clozapine levels in a patient with inflammation and infection.

A 23-year old male with a history of schizophrenia treated with clozapine 900 mg/d was admitted to the hospital for a gastrointestinal infection. The trough serum concentration of clozapine at admission was 9074 nmole/L, that is, almost 4-fold the upper limit of the reference range. The patients did not report any adverse effects of clozapine. The clozapine concentration 1 month earlier had been 1919 nmole/L, which is well within the reference range. There seems to be 2 different mechanisms explaining the increase in clozapine levels in this patient. First, a downregulation of CYP enzyme activities, which primarily seems to be mediated by interleukin-6, takes place during infection and inflammation. Second, the concentration of the acute phase protein α1-acid glycoprotein (AGP; orosomucoid) increases during infection and inflammation. As approximately 95% of clozapine is bound to AGP, the concentration of clozapine will increase in parallel with the increase in AGP. A therapeutic drug monitoring analysis measures the total drug concentration (ie, the concentration of unbound plus plasma protein bound drug), whereas the concentration of free drug exerts its pharmacological effects. Thus, this second mechanism will, in contrast to the first mechanism, not affect the clinical effect of clozapine. Although the patient was also treated with ciprofloxacin, which has been reported to inhibit the metabolism of clozapine, the clozapine levels did not further increase. This case illustrates the complex interrelationship between serum levels of clozapine and an intercurrent infection treated with potentially interacting antibiotics.

[Toxicological screening of medicines and drugs of abuse in emergency cases]. / Legemiddel- og rusmiddelanalyser som øyeblikkelig hjelp.

BACKGROUND: In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine. MATERIAL AND METHODS: The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediate quantitative analysis of between 80 and 90 substances. We here present the service in further detail and evaluate its usefulness during its first full year, 2005. Two case reports are presented to further illustrate the possible benefits of this service. RESULTS: Urgent testing was requested for a total of 390 samples; 351 serum and 39 urine samples. The most common indications for requesting such analyses were suspected acute intoxication (46%) and suspected therapeutic failure/adverse drug reaction (31%). 88% of the serum samples obtained for acute intoxications were positive, and 48 different substances were detected. The substances most often found were various benzodiazepines, various antiepileptic drugs, ethanol, carisoprodol, lithium, and other psychotropic drugs. In urine, amphetamine and zopiclone were the substances most often detected. INTERPRETATION: The service seems to be used according to its intentions, and the high number of samples received indicate that clinicians consider the service to be useful. An early and continuous dialogue between the clinician and the laboratory physician is a prerequisite for rational use of the service.

[On-site testing for drug abuse in urine]. / Bruk av hurtigtester for påvisning av rusmidler i urin.

BACKGROUND: There is an increasing interest in on-site testing for drugs of abuse. METHODS: Based upon our own experience and published literature, we have reviewed advantages and disadvantages of such tests. On-site testing is also evaluated in relation to the recommendations for urinary testing of drugs of abuse from the Norwegian Health Authorities. RESULTS: The most significant advantage with on-site testing is provision of rapid results, usually within 5-10 minutes. Disadvantages are the risks of false positive and false negative results, the fact that numerous drugs cannot be tested for, and the limited possibilities to detect manipulation. According to Norwegian regulations, on-site testing can be used for medical purposes, but cannot be used as the only method if a positive result may cause sanctions such as e.g. exclusion from school, job dismissal or loss of parental rights. There are also special requirements for the organization of such testing. INTERPRETATION: Before starting on-site testing for drugs of abuse, it should be considered if such testing is allowed or discouraged in the specific case. It is mandatory to know how the specific test works and to have routines for follow-up of positive test results.