Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial

BACKGROUND: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (C(max)). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. METHODS: This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30(®)]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. RESULTS: Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) C(max )reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in C(max )reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial. CONCLUSIONS: The observed reduction in C(max )is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00254800

Effects of oil and oil burn residues on seabird feathers

It is well known, that in case of oil spill, seabirds are among the groups of animals most vulnerable. Even small amounts of oil can have lethal effects by destroying the waterproofing of their plumage, leading to loss of insulation and buoyancy. In the Arctic these impacts are intensified. To protect seabirds, a rapid removal of oil is crucial and in situ burning could be an efficient method. In the present work exposure effects of oil and burn residue in different doses was studied on seabird feathers from legally hunted Common eider (Somateria mollissima) by examining changes in total weight of the feather and damages on the microstructure (Amalgamation Index) of the feathers before and after exposure. The results of the experiments indicate that burn residues from in situ burning of an oil spill have similar or larger fouling and damaging effects on seabird feathers, as compared to fresh oil

FILLING THE GAPS: SHAPING LIGHTING EDUCATION FOR THE FUTURE:LIGHTING METROPOLIS WP6.1

Training and knowledge of lighting is an increasingly sought-after professional quality in Denmark and Sweden. However, technological development in the lighting field has been in recent years extremely rapid, not least in Scandinavia. This has led to a situation, where users, designers, specifiers, buyers and installers are often neither in possession, nor have access to, the knowledge about lighting that they need. The aim of the study is to map and analyze the existing offer and demand for competencies within lighting related fields. That is to say, the study has looked at the existing educational programs within a broad field of lighting and compared this ‘supply’ to the current ‘demand’ by local employers. The paper presents the results from a statistical analysis of data collected from a series of surveys, expert interviews and focus groups, involving more than 250 participants in Sweden and Denmark. Based on the findings, the paper presents recommendations for the design of educational curricula

Treatment of Zygomatic Complex Fractures with Surgical or Nonsurgical Intervention:A Retrospective Study

Objective:Evaluate the 1-year treatment outcome of zygomatic complex fractures with surgical or nonsurgical intervention.Materials and Methods:One hundred and forty-two consecutive patients with a zygomatic complex fracture were enrolled. Sixty-eight patients underwent surgical intervention and 74 patients nonsurgical intervention. The 1-year examination evaluated cosmetic and functional outcome including malar symmetry, ocular motility, occlusion, mouth opening, neurosensory disturbances, and complications.Results:Forty-six patients allocated to surgical intervention responded to the 1-year follow-up examination. Satisfying facial contour and malar alignment was observed in 45 patients. All patients presented with identical position of the eye globe without enophthalmos and normal ocular movement. A habitual occlusion was seen in all patients with a mean interincisal mouth opening without pain of 49 mm. One patient presented with minor ectropion. Wound infection occurred in five patients. Persistent infraorbital neurosensory disturbance was described by 19 patients. The 1-year radiographic examination showed adequate fracture alignment in all patients with satisfying facial contour. However, dissimilar position of the orbital floor was seen in three patients having orbital reconstruction. None of the patients were re-operated or needed secondary correction of the zygomatic complex or orbital floor.Conclusion:Surgical intervention is an effective treatment modality of depressed zygomatic complex fractures, whereas a nonsurgical approach is often used for nondisplaced fractures. Most zygomatic complex fractures can be treated solely by an intraoral approach and rigid fixation at the zygomaticomaxillary buttress. Further exposure of the zygomaticofrontal junction or inferior orbital rim is necessary for severely displaced fractures, which require additional fixation.</jats:sec

Differential effects of glucagon-like peptide-1 receptor agonists on heart rate

Abstract While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N\ua0=\ua01112; active-treatment arms). HR effects observed in two independent head-to-head trials of lixisenatide and liraglutide (N\ua0=\ua0202; active-treatment arms) are also reviewed. Short-acting GLP-1 RAs, exenatide and lixisenatide, are associated with a transient (1\u201312\ua0h) mean placebo- and baseline-adjusted 24-h HR increase of 1\u20133\ua0beats per minute (bpm). Conversely, long-acting GLP-1 RAs are associated with more pronounced increases in mean 24-h HR; the highest seen with liraglutide and albiglutide at 6\u201310\ua0bpm compared with dulaglutide and exenatide LAR at 3\u20134\ua0bpm. For both liraglutide and dulaglutide, HR increases were recorded during both the day and at night. In two head-to-head comparisons, a small, transient mean increase in HR from baseline was observed with lixisenatide; liraglutide induced a substantially greater increase that remained significantly elevated over 24\ua0h. The underlying mechanism for increased HR remains to be elucidated; however, it could be related to a direct effect at the sinus node and/or stimulation of the sympathetic nervous system, with this effect related to the duration of action of the respective GLP-1 RAs. In conclusion, this review indicates that the effects on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated with a modest and transient HR increase before returning to baseline levels, while some long-acting GLP-1 RAs are associated with a more pronounced and sustained increase during the day and night. Findings from recently completed trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, does not present an increased cardiovascular risk for subjects with T2DM, although a pronounced increase in HR may be associated with adverse clinical outcomes in those with advanced heart failure

The utilisation of regulated standardised care packages by Danish chiropractors: a mixed methods study

BackgroundIn Denmark, chiropractors in primary care work as independent private contractors regulated by the Danish National Health Authorities. The regulation includes partial reimbursement intended for standardised care packages for lumbar and cervical radiculopathy and lumbar spinal stenosis. Random checks have shown lower use than expected. This study aimed to describe and explore the utilisation of standardised chiropractic care packages and identify barriers to uptake.MethodsA convergent mixed-method design was conceptualised. The use of standardised care packages was collected by register data. Potential determinants of difference in utilisation were assessed using a modified version of the Determinants of Implementation Behaviour Questionnaire (DIBQ) divided into 13 domains and sent to chiropractors in private clinics in Denmark in 2019. An open-ended question was added to the questionnaire, and thematic content analysis was applied. Qualitative findings were used to expand on the DIBQ data providing further insight into the clinicians’ perspective on standardised care packages. ResultsRegistry data of 244 included chiropractic clinics showed limited and inconsistent use of the standardised chiropractic care packages. A total of 269 chiropractors (44%) answered the DIBQ, and 45 provided data for the qualitative analyses. At least 60% of the clinicians answered ‘Strongly agree’ or ‘Agree’ in 10 out of 13 DIBQ domains suggesting a positive attitude towards using the standardised care packages. Three domains were identified as ‘problematic’ as more than 20% of clinicians disagreed or strongly disagreed: ‘Socio-political context’, ‘Goals’ and ‘Innovation’. Qualitative findings indicated that lack of usage of the standardised care packages was mainly related to the practical organization of standardised care, the chiropractor’s role when managing patients, and the patient population of interest to the clinic (e.g., children, athletes).ConclusionIn general, Danish chiropractors displayed positive attitudes towards standardised packages of care. However, considerable variation in the use of the standardised care programs was observed. Low utilisation seemed mainly related to logistics, the chiropractor’s role, collaboration with GPs, and the patient population of interest to the clinic. These findings should be further explored in more extensive qualitative studies to inform implementation initiatives to increase and rectify utility

Review article: a comparison of glucagon-like peptides 1 and 2.

BACKGROUND: Recent advancements in understanding the roles and functions of glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting these peptides in therapeutic strategies. AIM: To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP-1 and GLP-2. METHODS: This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP-1 and GLP-2. RESULTS: Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit distinctive biological functions that are governed by the expression of their respective receptors, GLP-1R and GLP-2R. Through widespread expression in the pancreas, intestine, nervous tissue, et cetera, GLP-1Rs facilitates an incretin effect along with effects on appetite and satiety. GLP-1 analogues resistant to degradation by dipeptidyl peptidase-IV and inhibitors of dipeptidyl peptidase-IV have been developed to aid treatment of diabetes and obesity. The GLP-2R is expressed almost exclusively in the stomach and bowel. The most apparent role for GLP-2 is its promotion of growth and function of intestinal mucosa, which has been targeted for therapies that promote repair and adaptive growth. These are used as treatments for intestinal failure and related conditions. CONCLUSIONS: Our growing understanding of the biology and function of GLP-1, GLP-2 and corresponding receptors has fostered further discovery of fundamental biological function as well as new categories of potent therapeutic medicines

Effect of renal impairment on the pharmacokinetics of exenatide

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