Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of 20 mg melatonin as an adjuvant therapy in women with endometriosis-associated pain. This randomized double-blinded, placebo-controlled trial was conducted at the Research Center for Womens Health at Sodersjukhuset, a university hospital in Stockholm, Sweden. Forty women from 18 to 50 years of age with endometriosis and severe dysmenorrhea with or without chronic pelvic pain were given 20 mg Melatonin or placebo orally daily for two consecutive menstrual cycles or months. The level of pain was recorded daily on the 11-point numeric rating scale, a difference of 1.3 units was considered clinically significant. Clincaltrials.gov nr NCT03782740. Sixteen participants completed the study in the placebo group and 18 in the melatonin group. The difference in endometriosis-associated pain between the groups showed to be non-significant statistically as well as clinically, 2.9 (SD 1.9) in the melatonin group and 3.3 (SD 2.0) in the placebo group, p = 0.45. This randomized, double-blinded, placebo-controlled trial could not show that 20 mg of melatonin given orally at bedtime had better analgesic effect on endometriosis-associated pain compared with placebo. No adverse effects were observed.

Purpose Dysmenorrhea is a common, recurring, painful condition with a global prevalence of 71%. The treatment regime for dysmenorrhea includes hormonal therapies and NSAID, both of which are associated with side effects. A dose of 10 mg melatonin daily has previously been shown to reduce the level of pelvic pain in women with endometriosis. We chose to investigate how this regime, administered during the week of menstruation, would affect women with dysmenorrhea but without any signs of endometriosis, as adjuvant analgesic treatment. Methods Forty participants with severe dysmenorrhea were randomized to either melatonin or placebo, 20 in each group. Our primary outcome was pain measured with numeric rating scale (NRS); a difference of at least 1.3 units between the groups was considered clinically significant. Secondary outcomes were use of analgesics, as well as absenteeism and amount of bleeding. Mixed model was used for statistical analysis. Results Eighteen participants completed the study in the placebo group and 19 in the melatonin group. Mean NRS in the placebo group was 2.45 and 3.18 in the melatonin group, which proved to be statistically, although not clinically significant. Conclusion This randomized, double-blinded, placebo-controlled trial could not show that 10 mg of melatonin given orally at bedtime during the menstrual week had better analgesic effect on dysmenorrhea as compared with placebo. However, no adverse effects were observed.

Introduction Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education. Methods and analysis This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in >= 80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision. Ethics and dissemination The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO-ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.

The prescription of medicines is one of the most common acts performed by physicians. Yet, several studies have shown that junior doctors are not well prepared for the task. The teaching of basic and clinical pharmacology varies greatly between universities, both within Sweden and in Europe. National prescribing exams have been introduced in the UK, the Netherlands and Belgium, and there is an on-going project to develop a European exam, focusing on a list of essential medicines and patient safety. With the new six year curriculum for medical education in Sweden, the license to prescribe could be linked to a national prescribing exam, to ensure good knowledge of both therapeutics and Swedish drug regulation.

Läkemedelsverket rapporterar att man inte, utifrån sitt etablerade arbetssätt, kan genomföra nytta–riskvärdering av läkemedel utanför godkänd indikation. 

Sjukvården har ett behov av en nationell process för värdering av off label-användning av vissa läkemedel. 

Sjukvården behöver också fler och innovativa akademiskt drivna läkemedelsstudier.

Background

Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives.

Methods

This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linköping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18–40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC0–24h) was the main outcome measure.

Results

There were no significant differences in the studied pharmacokinetic parameters, AUC0–24h, total AUC, peak serum concentration (Cmax), time to peak serum concentrations (Tmax), apparent oral clearances of levonorgestrel (CLoral), or terminal half-lives (t½) between the groups.

Conclusion

This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached.

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Little is known about undergraduate education on antibiotic prescribing in Europe and even less about the antibiotic prescribing skills of nearly-graduated medical students. This study aimed to evaluate the antibiotic prescribing skills of final-year medical students across Europe and the education they received during medical training. In a cross-sectional study, final-year medical students from 17 medical schools in 15 European countries were asked to prescribe for two written case reports of infectious diseases (acute bronchitis and community-acquired pneumonia). The appropriateness of antimicrobial therapy was determined using a scoring form based on local guidelines. Teachers from each medical school were asked to complete a standardised questionnaire about the teaching and assessment of undergraduate education on antibiotic use. In total, 856 final-year medical students (95.6%) completed the assessment and 16 teachers (94.1%) completed the questionnaire. Overall, 52.7% (range 26-83%) of the 1.683 therapies prescribed were considered appropriate. The mean number of contact hours for undergraduate education on antimicrobials was 25.6 (range 2-90). Differences in education styles were found to have a significant impact on students performance, with a problem-based learning style being associated with more appropriate antimicrobial prescribing than a traditional learning style (46.0% vs. 22.9%; P amp;lt; 0.01). Although there are differences between medical schools, final-year medical students in Europe lack prescribing skills for two common infectious diseases, possibly because of inadequate undergraduate education on antibiotic use and general prescribing. To improve students skills, interactive teaching methods such as prescribing for simulated and real patients should be used. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

BackgroundPHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patients medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients.MethodsSide-effects included were sedation, constipation, orthostatic symptoms, anticholinergic and serotonergic effects. The alerts generated by PHARAO were tested in 745 persons 65years old. Dispensed prescriptions retrieved from the Swedish prescribed drug register were used to generate the pharmacological risk scores of patients medications. Symptoms possibly related to side-effects were extracted from medical records data.ResultsThe PHARAO system generated 776 alerts, most often for the risk of anticholinergic symptoms. The total specificity estimates of the PHARAO system were 0.95, 0.89 and 0.78 for high, intermediate and low risk alerts, respectively. The corresponding sensitivity estimates were between 0.12 and 0.37. The negative predictive value was 0.90 and the positive predictive value ranged between 0.20-0.25.ConclusionsThe PHARAO system had a high specificity and negative predictive value to detect symptoms possibly associated with the of patients medications, while the sensitivity and positive predictive value were low. The PHARAO system has the potential to minimise the risk of over-alerts in combination with a drug-drug interaction alert system, but should be used in connection with a medical evaluation of the patient.

A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment is a complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills. Acquiring professional confidence in the art of prescribing is essential during medical training. The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.e. the basics of prescribing. The confidence increased by the number of reviews and reports performed, i.e. the extent of practice (correlation coefficients: 0.41 and 0.38, respectively, both pamp;lt;0.0001), as did the extent of the students reflection on important aspects of drug treatment such as adherence, adverse reactions, renal function, dosing, and drug interactions. In multivariate regression analyses, major predictors for confidence in performing medication reviews were extent of practice and extent of clinical supervision. The results suggest that these factors are keys to acquiring professional confidence in the art of prescribing.

Introduction The provision of healthcare services is not dedicated to promoting maintenance of function and does not target frail older persons at high risk of the main causes of morbidity and mortality. The aim of this study is to evaluate the effects of a proactive medical and social intervention in comparison with conventional care on a group of persons aged 75 and older selected by statistical prediction.

Methods and analysis In a pragmatic multicentre primary care setting (n=1600), a prediction model to find elderly (75+) persons at high risk of complex medical care or hospitalisation is used, followed by proactive medical and social care, in comparison with usual care. The study started in April 2017 with a run-in period until December 2017, followed by a 2-year continued intervention phase that will continue until the end of December 2019. The intervention includes several tools (multiprofessional team for rehabilitation, social support, medical care home visits and telephone support). Primary outcome measures are healthcare cost, number of hospital care episodes, hospital care days and mortality. Secondary outcome measures are number of outpatient visits, cost of social care and informal care, number of prescribed drugs, health-related quality of life, cost-effectiveness, sense of security, functional status and ability. We also study the care of elderly persons in a broader sense, by covering the perspectives of the patients, the professional staff and the management, and on a political level, by using semistructured interviews, qualitative methods and a questionnaire.

Ethics and dissemination Approved by the regional ethical review board in Linköping (Dnr 2016/347-31). The results will be presented in scientific journals and scientific meetings during 2019–2022 and are planned to be used for the development of future care models.

Clinical pharmacology as a scientific discipline and medical specialty was unarguably born in the twentieth century. Whilst pharmacologythe science behind the treatment of diseasehad been in evolution since at least medieval times, the clinical discipline of pharmacology has had a more recent genesis and rather insidious evolution. During the 1900s, there were some clear father (parent) figures of clinical pharmacology in Europe that emerged and were responsible for the development of the specialty in this continent. This was a time when there were parallel developments in geographically dispersed academic departments (around the globe), during an age of excitement in drug discovery and clinical application of new therapeutic agents. It was the meeting of minds of some of these progenitors of the specialty that led to the development of the European Association for Clinical Pharmacology and Therapeutics (EACPT) 25years ago arising from a working party supported by the World Health Organization in Europe. The EACPT now includes all major national organizations for clinical pharmacology in Europe, representing over 4000 individual professionals interested in clinical pharmacology and therapeutics. The EACPT has a major interest in promoting the safe use of medicines across Europe and internationally and has supported these aims since 1995, through biennial international scientific congresses and summer schools with delegates and presenters from around the world as well as various working group activities. In this article, the current executive committee members of EACPT recall this history, describe the evolution of the association over the last quarter of a century, and provide an update on the activities and ambitions of the association today.

The aims of this study are to describe the development of PHARAO (Pharmacological Risk Assessment Online), a decision support system providing a risk profile for adverse events, associated with combined effects of multiple medicines, and to present data from a pilot study, testing the use, functionality, and acceptance of the PHARAO system in a clinical setting. About 1400 substances were scored in relation to their risk to cause any of nine common and/or serious adverse effects. Algorithms for each adverse effect score were developed to create individual risk profiles from the patients list of medication. The system was tested and integrated to the electronic medical record, during a 4-month period in two geriatric wards and three primary healthcare centers, and a questionnaire was answered by the users before and after the test period. A total of 732 substances were tagged with one or more of the nine risks, most commonly with the risk of sedation or seizures. During the pilot, the system was used 933 times in 871 patients. The most common signals generated by PHARAO in these patients were related to the risks of constipation, sedation, and bleeding. A majority of responders considered PHARAO easy to use and that it gives useful support in performing medication reviews. The PHARAO decision support system, designed as a complement to a database on drug-drug interactions used nationally, worked as intended and was appreciated by the users during a 4-month test period. Integration aspects need to be improved to minimize unnecessary signaling.

Drug-drug interactions are increasingly common, as patients are getting older and the number of drugs per patient is increasing. In this study, we investigated to which extent potential drug-drug interactions originated from single or multiple prescribers. All patients attending any of 20 primary healthcare centres were included in a retrospective observational cohort study. Data on all prescriptions to these patients, irrespectively of the prescriber, were collected for two 4-month periods. Potential drug interactions were identified using the drug-drug interaction database SFINX. Interactions were classified with respect to the workplace of the prescriber, and the prevalence of interactions according to origin was analysed. We found that the drug interactions were significantly more common when the drugs were prescribed from different healthcare centres, compared with drugs prescribed from the patients' primary healthcare centre only. One explanation for this increased risk of drug interactions could be that the prescribers at different primary healthcare centres do not share the same information concerning the total medication list of the patient.

Background: The aim of this study was to compare use of references in responses from Scandinavian drug information centres (DICs). Methods: Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The six queries concerned adverse effects, pharmacokinetics, pregnancy, complementary medicine, polypharmacy, and breast feeding. References in the responses were categorised into five types of drug information sources: primary (original studies), secondary (reviews), tertiary (drug monographs, handbooks, etc.), DIC database, or personal communication. Results: Two hundred and forty-four references were used in the 42 responses. The mean number of references varied from 3.0 to 10.6 for the six queries. The largest difference between centres with regard to number of references used (range 1?17) was found for the query on complementary medicine. In total, 124 references (50.8%) were tertiary, and only 10 of the 42 responses (23.8%) did not have any tertiary references included. Complementary medicine, breast feeding, and pregnancy were query types associated with relatively frequent use of primary references. Use of DIC database was not uncommon, but personal communications were seldom used. Conclusions: Scandinavian DICs differ substantially in number and type of references to identical drug-related queries. Tertiary sources are mainly preferred irrespective of type of query.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.

Purpose: The aims of this study were to assess the quality of responses produced by drug information centers (DICs) in Scandinavia, and to study the association between time consumption processing queries and the quality of the responses. Methods: We posed six identical drug-related queries to seven DICs in Scandinavia, and the time consumption required for processing them was estimated. Clinical pharmacologists (internal experts) and general practitioners (external experts) reviewed responses individually. We used mixed model linear regression analyses to study the associations between time consumption on one hand and the summarized quality scores and the overall impression of the responses on the other hand. Findings: Both expert groups generally assessed the quality of the responses as "satisfactory" to "good." A few responses were criticized for being poorly synthesized and less relevant, of which none were quality-assured using co-signatures. For external experts, an increase in time consumption was statistically significantly associated with a decrease in common quality score (change in score, -0.20 per hour of work; 95% CI, -0.33 to -0.06; P = 0.004), and overall impression (change in score, -0.05 per hour of work; 95% CI, -0.08 to -0.01; P = 0.005). No such associations were found for the internal experts assessment. Implications: To our knowledge, this is the first study of the association between time consumption and quality of responses to drug-related queries in DICs. The quality of responses were in general good, but time consumption and quality were only weakly associated in this setting. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.

Purpose: The aim of the present study was to investigate how prescribers and pharmacists use and perceive the drug-drug interaction database SFINX in their clinical work. Methods: A questionnaire was developed with questions aimed at the usage of SFINX, and the perceptions of the database. The questionnaire was sent out to all registered users of the web application of SFINX. The anonymous answers from the target users, prescribers and pharmacists were summarized using descriptive statistics. Statistical analysis was performed on age and gender differences for some questions regarding different usage patterns. Results: The questionnaire was sent to 11,763 registered SFINX users. The response rate was 23%, including 1871 answers from prescribers or pharmacists. SFINX was reported to be used at least weekly or more often by 45% of the prescribers and 51% of the pharmacists. Many prescribers reported using the database during the patient consultation (60%) or directly before or after (56%). Among the prescribers, 74% reported that the information received made them change their action at least sometimes. About 20% of the prescribers and 25% of the pharmacists considered the information as irrelevant sometimes or more often. Conclusion: Most prescribers and pharmacists reported using SFINX in direct association with a patient consultation. Information received by using SFINX makes prescribers and pharmacists change their handling of patients. DDI databases with relevant information about patient handling might improve drug treatment outcome. (C) 2015 Elsevier Ireland Ltd. All rights reserved.