Review of clinical pharmacokinetics and pharmacodynamics of clonidine as an adjunct to opioids in palliative care.

Clonidine is an α-adrenoceptor agonist acting on receptors in the brain and peripheral tissues, leading to a reduction in sympathetic outflow and release of certain neurotransmitters. Clonidine has multiple uses across various medical conditions. One of its uses is as adjuvant to anaesthetic and analgesic agents specially opioids, mostly administered through intravenous and epidural routes. The opioids, effective in cancer pain management, are associated with various side effects such as sedation, pruritus, constipation, nausea, respiratory depression, tolerance and dependence. Combination of clonidine with opioids seems to help to achieve better pain management and less need of opioids. Use of clonidine in palliative care has been less common, but it is gradually gaining recognition for its potential benefits in managing symptoms like cancer pain and agitation. This combination approach has been explored in palliative care settings, including cancer pain and agitation, where patients experience complex and refractory symptoms. It seems to be well tolerated and gives better symptom relief. The available literature on clonidine's use in cancer pain and agitation management, especially in subcutaneous form, is limited and outdated. Therefore, the optimal dosing, safety profile and overall effectiveness of subcutaneous clonidine requires further exploration through prospective research studies.

External validation of the Medication Risk Score in polypharmacy patients in general practice: A tool for prioritizing patients at greatest risk of potential drug-related problems.

Drug-related problems are important causes of patient harm and increased healthcare costs. To assist general practitioners in prioritizing patients in need of a critical medication review, we aimed to assess the ability of the Medication Risk Score (MERIS) to stratify patients with polypharmacy in general practice according to their risk of drug-related problems. We conducted a cross-sectional multi-centre external validation study. Patients receiving more than five concomitant medications (polypharmacy) were eligible. The outcome was potentially serious drug-related problems as evaluated by expert consensus. Performance was assessed in terms of calibration and discrimination indices. Of 497 patients, 489 were included in the main analysis. The median age (interquartile range) was 70.5 years (60-79). In total, 372 potentially serious drug-related problems were observed in 253 patients (52%). The MERIS was well calibrated above a score level of 10. The area under the receiver operating characteristic curve was 0.70 (95% confidence interval: 0.65-0.74). The performance of the MERIS was fair in patients with polypharmacy in general practice. Given the scale of drug-related problems and the lack of efficient prioritization tools in this setting, the MERIS could be a useful risk indicator to complement usual practice.

[Local anaesthesia and steroid blockades for carpal tunnel syndrome in pregnancy].

The possible impact on the foetus must always be taken into account, whenever non-conservative strategies are considered in pregnancy. As to carpal tunnel syndrome, surgery is usually reserved for severe cases, or when steroid blockades have been insufficient. If only pharmacological considerations are taken into account, surgery with local anaesthetics may however be preferred over blockades. While especially lidocaine is considered quite safe in pregnancy, a foetal risk cannot be ruled out for the synthetic glucocorticoids. Moreover, the duration of exposure is considerably shorter. These issues are summarized and discussed in this review.

The Danish model for the quick and safe implementation of infliximab and etanercept biosimilars.

PURPOSE: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept). METHODS: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation. RESULTS: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds. CONCLUSION: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.