Adherence to risk management guidelines for drugs which cause vitamin D deficiency - big data from the Swedish health system.

PURPOSE: Several medications are known to cause vitamin D deficiency. The aim of this study is to describe vitamin D testing and supplementation in patients using these "risk medications", thereby assessing adherence to medical guidelines. PATIENTS AND METHODS: A database with electronic health records for the population in a Swedish County (≈240,000 inhabitants) was screened for patients prescribed the pre-defined "risk medications" during a 2-year period (2014-2015). In total, 12,194 patients were prescribed "risk medications" pertaining to one of the three included pharmaceutical groups. Vitamin D testing and concomitant vitamin D supplementation, including differences between the included pharmaceutical groups, was explored by matching personal identification numbers. RESULTS: Corticosteroids were prescribed to 10,003 of the patients, antiepileptic drugs to 1,101, and drugs mainly reducing vitamin D uptake to 864. Two hundred twenty-six patients were prescribed >1 "risk medication". Seven hundred eighty-seven patients (6.5%) had been tested during the 2-year period. There were no differences regarding testing frequency between groups. Concomitant supplements were prescribed to 3,911 patients (32.1%). It was more common to be prescribed supplements when treated with corticosteroids. Vitamin D supplementation was more common among tested patients in all three groups. Women were tested and supplemented to a higher extent. The mean vitamin D level was 69 nmol/L. Vitamin D deficiency was found in 24.1% of tested patients, while 41.3% had optimal levels. It was less common to be deficient and more common to have optimal levels among patients prescribed corticosteroids. CONCLUSION: Adherence to medical guidelines comprising testing and supplementation of patients prescribed drugs causing vitamin D deficiency needs improvement in Sweden.

[Practical management of nosebleed]. / ABC om - Praktisk handläggning av näsblödning.

This article presents the guidelines for the treatment of epistaxis in an out-patient setting in Sweden. Nasal hemorrhage from the anterior part of the nasal cavity is best treated with silver nitrate cauterization or electrocautery. Bleeding from the posterior part of the nasal cavity often requires treatment with a pneumatic nasal tamponade, RapidRhino, or a posterior nasal packing with a Foley catheter. When a patient requires treatment with posterior nasal packing it is recommended that a contact be taken with the nearest ENT clinic. The guidelines described are used by otorhinolaryngologists at Karolinska University Hospital, Stockholm, Sahlgrenska University Hospital, Gothenburg, Lund University Hospital, Lund and District Hospital Sundsvall-Härnösand, Sundsvall.

Exercise intervention for the treatment of trismus in head and neck cancer - a prospective two-year follow-up study.

Background This study aims to investigate the long-term effects of structured trismus intervention in patients with head and neck cancer (HNC) and trismus in terms of mouth opening, trismus-related symptoms and health-related quality of life (HRQL). Material and methods Fifty patients with HNC to receive radiotherapy ± chemotherapy were included in this prospective study along with a matched control group. The intervention group received a 10-week structured exercise with a jaw mobilizing device (TheraBite® jaw device or Engström device). Patients were assessed before and after trismus exercise intervention and at a two-year follow-up. Primary endpoint was maximum interincisal opening (MIO) and secondary endpoints included trismus-related symptoms and HRQL assessed with patient-reported outcome (PRO)-instruments [Gothenburg Trismus Questionnaire (GTQ), European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the related HNC-specific module the EORTC Head & Neck Questionnaire (EORTC QLQ-H&N35)]. Results The intervention group had a higher MIO at the two-year follow-up compared to the control group (40.5 mm and 34.3 mm, respectively), which was statistically significant. The intervention group also reported less jaw-related problems according to the GTQ and higher functioning as measured by EORTC QLQ-C30 and QLQ-H&N35 compared to the control group. Conclusion A positive persistent effect of exercise intervention for trismus in HNC patients was found with regard to MIO, trismus-related symptoms and HRQL. Exercise intervention is important in long-term treatment of radiation-induced trismus in HNC patients. The trismus-specific questionnaire, GTQ, is a valuable tool for observing and evaluating trismus over time.

Characterisation of the human liver in vitro metabolic pattern of artemisinin and auto-induction in the rat by use of nonlinear mixed effects modelling.

AIMS: The aims of the study were to characterise the metabolic pattern of artemisinin in human and rat liver microsomes and to assess the magnitude of auto-induction in the rat. METHODS: (14)C-artemisinin was incubated with human liver microsomes and with liver microsomes from rats pretreated with oral artemisinin or placebo. The metabolic fate of (14)C-artemisinin in microsomes from human B-lymphoblastoid cell lines transformed with CYP2A6, CYP2B6 and CYP3A4 was also investigated. The human liver microsome data and the rat liver microsomes data were analysed by nonlinear mixed effects modelling and naïve pooling using NONMEM, respectively. RESULTS: Four metabolites were radiometrically detected in experiments with rat liver microsomes. The model that best described the data involved three primary metabolites of which one metabolite was further metabolised to a secondary metabolite. The formation of the four metabolites was induced 2.8, 7.2, 4.8 and 2.5-fold, respectively, in liver microsomes from rats pre-treated with artemisinin. Three metabolites were formed in human liver microsomes; having the same retention times as three of the metabolites formed in the rat. The final model consisted of two primary metabolites and a secondary metabolite with CYP2B6 and CYP2A6 influencing the formation rates of the major and minor primary metabolites, respectively. CONCLUSIONS: CYP2B6 and CYP2A6 activities described variability in the formation of the major and minor primary metabolites, respectively, in human liver microsomes. All artemisinin metabolic pathways in rat liver microsomes were induced in artemisinin pretreated animals. We suggest modelling as a method for the discrimination and detection of more complex metabolic patterns from in vitro metabolism rate data.

Population pharmacokinetic and pharmacodynamic modelling of artemisinin and mefloquine enantiomers in patients with falciparum malaria.

OBJECTIVES: The aims of this study were to investigate whether artemisinin influences the pharmacokinetics of mefloquine enantiomers or vice versa and to model the antiparasitic effect of these drugs alone and in combination in Plasmodium falciparum malaria patients. METHODS: Forty-two male and female patients were randomised to treatment with either oral artemisinin 500 mg daily for 3 days followed by oral mefloquine 750 mg on day 4, oral artemisinin 500 mg daily for 3 days plus oral mefloquine 750 mg on day 1 or a single 750-mg oral dose of mefloquine. The data was modelled using NONMEM. RESULTS: All patients were successfully treated regardless of treatment. The fastest parasite clearance rates were observed in patients receiving artemisinin together with mefloquine on the first day of treatment. A pharmacodynamic model based on the life cycle of P. falciparum successfully described the efficacy of artemisinin, mefloquine and the combination. The time artemisinin concentration stays above a minimum inhibitory concentration was estimated to 2.97 h (relative standard error 4.7 h). The two mefloquine enantiomers exhibited different pharmacokinetics, with an oral clearance of 3.51 (7.9) l/h and 0.602 (6.9) l/h for RS-mefloquine and SR-mefloquine, respectively. In patients receiving only artemisinin the first 3 days, artemisinin oral clearance was 6.9-fold higher the last day of treatment compared with the first day. There was no difference in the pharmacokinetics of mefloquine enantiomers when mefloquine was given alone, in combination with artemisinin or after a 3-day regimen of artemisinin. There was a tendency towards, although non-significant, higher artemisinin concentrations when artemisinin was given together with mefloquine compared with when given alone. CONCLUSIONS: No significant pharmacokinetic interactions were observed after co-administration of artemisinin and mefloquine. The P. falciparum malaria pharmacodynamic model successfully described the antimalarial effect of artemisinin, mefloquine and a combination of the two drugs.