Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [¹¹C]DASB and [¹¹C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.

Introduction: Misoprostol (Cytotec) was primarily made for treating gastric ulcers. However today it is mostly used for abortion, treating postpartum hemorrhage, and for induction of labor. The tablet contains 200 µg of misoprostol, yet the dosages used for induction of labor are much smaller (25–50 µg), leading to uncertainty of dosage in daily use.

Aim: To evaluate and compare the relative bioavailability of two misoprostol products (Angusta 25 µg and Cytotec 200 µg tablets) administered orally or sublingually given in a daily clinical setting to women admitted for induction of labor at term.

Methods: Women carrying a live, singleton fetus in a cephalic position and with a gestational age between 259 and 296 days were included. Blood samples were collected at 0, 5, 10, 20, 30, 40, 50, 75, 100, 120, 180, and 240 minutes. A serum analytical assay was performed and pharmacokinetic parameters were calculated. Patients were assigned to one of three groups.

Results: A total of 72 patients were included. No significant differences demographic characteristics were found. The ratios for AUC, AUC (0−t), and Cmax were similar in all three groups, but CI-values were outside the required 80–125%. Sublingual administration yielded a 20–30% higher bioavailability and a 50% higher Cmax than compared to the oral route.

Conclusion: The relative bioavailability between Angusta and Cytotec could not be confirmed as being equal at the 25 µg or 50 µg level because the 90% CI-values when comparing the ratios for AUC, AUC(0−t), and Cmax were wider than accepted. The reason for this could be the real-life, non-standardized circumstances in which the study was conducted. Sublingual administration seems to have higher bioavailability than oral administration. More studies are needed to ascertain an optimal dosage regime balancing both safety and efficacy for mother and child.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02516631.

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.

Att behandla med läkemedel är en kärnuppgift för läkare; grundutbildningen behöver ge studenterna förutsättningar att klara detta.

Enkätresultat från fyra lärosäten visade att 45 procent av studenterna efter sin invärtesmedicinska placering kände sig trygga med att göra läkemedelsgenomgångar och 62 procent med att skriva läkemedelsberättelser.

Studenter som gör många läkemedelsgenomgångar/läkemedelsberättelser känner större trygghet och reflekterar mer över patientens behandling.

Klinisk handledning gör skillnad.

När kursplaner revideras vid införandet av en sexårig läkarutbildning, med förskrivningsrätt direkt efter examen, behöver klinisk träning i läkemedelsarbete inklusive handledning tydliggöras.

The article discusses possible effects of the use of analgesics during pregnancy. It summarizes the pertinent literature and reports some previously unpublished data from the Swedish Medical Birth Register. Most likely the use of analgesics does not cause spontaneous abortion. Only small malformation risk increases are seen after the use of opioids and perhaps non-steroid anti-inflammatory drug (NSAID) use. If possible, the latter should be avoided during the first trimester. If exposure has occurred there is no reason to consider an interruption of the pregnancy. Continued use of analgesics may increase the risk of preeclampsia and of preterm birth, especially valid for opioids. Use of acetylsalicylic acid (ASA) in late pregnancy should be avoided because of the risk of bleeding and (valid also for NSAIDs) premature closure of the ductus arteriosus. A small risk for neonatal abstinence syndrome may exist after the use of opioids for chronic pain, notably during the third trimester and long-lasting effects on child development can possibly occur. For a woman with chronic pain, adequate use of pain killers during pregnancy is needed. It is prudent to avoid ASA and NSAIDs towards the end of the pregnancy, while acetaminophen is an acceptable option all through pregnancy. If continued use of opioids is necessary, the associated risks are low. Triptans can be used for migraine during pregnancy. If possible sumatriptan is preferable to other triptans as data for the latter are largely lacking. Ergots are preferably avoided as not enough data are available.

Background: There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences. Methods: An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. Results: The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. Conclusions: The results offer a base of understanding the students perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.

Background

The overall aim of the study was to explore health care students´ understanding of core concepts in pharmacology.

Method

An interview study was conducted among twelve students in their final semester of the medical program (n = 4), the nursing program (n = 4), and the specialist nursing program in primary health care (n  = 4) from two Swedish universities. The participants were individually presented with two pharmacological clinically relevant written patient cases, which they were to analyze and propose a solution to. Participants were allowed to use the Swedish national drug formulary. Immediately thereafter the students were interviewed about their assessments. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was used to identify units of meaning in each interview. The units were organized into three clusters: pharmacodynamics, pharmacokinetics, and drug interactions. Subsequent procedure consisted of scoring the quality of students´ understanding of core concepts. Non-parametric statistics were employed.

Results

The study participants were in general able to define pharmacological concepts, but showed less ability to discuss the meaning of the concepts in depth and to implement these in a clinical context. The participants found it easier to grasp concepts related to pharmacodynamics than pharmacokinetics and drug interactions.

Conclusion

These results indicate that education aiming to prepare future health care professionals for understanding of more complex pharmacological reasoning and decision-making needs to be more focused and effective.

Only few studies exist regarding the risk of a teratogenic effect of tramadol when used in early pregnancy. Using the Swedish Medical Birth Register, women (deliveries in 1997-2013) who had reported the use of tramadol in early pregnancy were identified. Maternal characteristics and concomitant drug use were analyzed. Among 1,682,846 women (1,797,678 infants), 1751 (1776 infants) had used tramadol, 96 of the infants had a congenital malformation and 70 of them were relatively severe. The adjusted odds ratio for a relatively severe malformation was 1.33 (95% CI 1.05-1.70). The odds ratios for cardiovascular defects (1.56, 95% CI 1.04-2.29) and for pes equinovarus (3.63, 95% CI 1.61-6.89) were significantly increased. The study suggests a teratogenic effect of tramadol but the risk increase is moderate. (C) 2015 Elsevier Inc. All rights reserved.

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.

Objectives To investigate the proposed synergistic teratogenic effect of use of selective serotonin receptor inhibitors (SSRI) together with sedatives or hypnotics, primarily benzodiazepines, during pregnancy.

Design Cohort study of congenital malformations after maternal use of SSRI, sedatives/hypnotics or the combination of the two drug categories.

Setting Swedish national health registers.

Participants A total of 10 511 infants born of women who had used SSRI drugs but no other central nervous system (CNS)-active drug, 1000 infants born of women who had used benzodiazepines and no other CNS-active drug, and 406 infants whose mothers had used both SSRI and benzodiazepines but no other CNS-active drug.

Results None of the three groups showed a higher risk for any relatively severe congenital malformation or any cardiac defect when comparison was made with the general population risk (adjusted risk ratio (RR) for the combination of SSRI and benzodiazepines and a relatively severe malformation=1.17 (95% CI 0.70 to 1.73). Similar results were obtained for the combination of SSRI with other sedative/hypnotic drugs.

Conclusions The previously stated increased risk associated with the combined use of these drug categories, notably for a cardiac defect, could not be replicated.

Artikelförfattarna har genomfört en pedagogisk hypotesgenererande studie om de medicinska utbildningarna. Deras slutsats är att studenterna behöver bättre förutsättningar för att tillägna sig kunskaper, färdigheter och förhållningssätt i ämnen som anatomi, fysiologi och farmakologi.