The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

AIMS: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. METHODS: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. RESULTS: Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. CONCLUSIONS: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

A review of the sampling methodology used in studies evaluating the effectiveness of risk minimisation measures in Europe.

PURPOSE: This review aims to describe the sampling methodology used in studies assessing effectiveness of risk minimisation measures (RMMs) in the European Union. METHODS: The European Union electronic Register of Post-Authorization Studies (EU PAS Register) was searched to identify studies that assessed the effectiveness of RMMs and recruited a target population of healthcare professionals (HCPs), sites or patients. Studies with both protocol and report were included and data was extracted from these documents to describe study characteristics and variables involved in the sampling methodology. RESULTS: Out of 1092 studies finalised between June 2017 and May 2019, 17 studies were eligible for review. Thirteen were surveys, three chart reviews and one combined both methodologies. All the 17 studies recruited HCPs/sites and 8 of them also recruited patients. The most common rationale for country sampling was market uptake (10/17), while for HCP/site sampling, it was representativeness of the prescribing practices (14/17). Only a minority of the studies (4/17) provided supporting evidence to inform this theoretical framework. HCP/site sampling frames were mainly network of physicians (5/17) or HCP databases (5/17), with only one study providing a detailed description of the sampling frame. HCPs were selected mainly using probabilistic sampling (10/17) and patients using non-probabilistic sampling (6/8). Only a few studies compared participating with non-participating HCPs/sites (5/17) and patients (3/8). Eight studies reported that their results were generalisable. CONCLUSIONS: Overall, the study documents provided insufficient details to understand the rationale behind the sampling decisions. More standardisation and guidance in reporting the sampling strategy and operational considerations applicable to these types of studies would support transparency and facilitate the evaluation of representativeness of the study results.

Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.

Endothelin-1 (ET-1) is a newly described pain mediator that is involved in the pathogenesis of pain states ranging from trauma to cancer. ET-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. While it is able to trigger pain through its actions on endothelin-A (ET(A)) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET(B)) receptors. Here we map a new endogenous analgesic circuit, in which ET(B) receptor activation induces the release of beta-endorphin from keratinocytes and the activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs, also named Kir-3) linked to opioid receptors on nociceptors. These results indicate the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and establish keratinocytes as an ET(B) receptor-operated opioid pool.