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Retinoid-based drugs, while effective, are associated with systemic toxicity. Topical alternatives offer a safer option, and tazarotene, a third-generation synthetic retinoid, holds promise. This study investigates tazarotene's transdermal delivery potential, focusing on its application for joint-related conditions. The aim of this study was to investigate the suitability of tazarotene as a candidate for transdermal delivery into joints. In vitro permeation studies, using porcine skin, assessed tazarotene's transdermal drug delivery from solution and gel formulations. A tape-stripping analysis determined stratum corneum retention and a pilot study using porcine joints assessed tazarotene's ability to reach articular cartilage. Ultra Performance Liquid Chromatography coupled with a mass detector method was used to quantify tazarotene and tazarotenic acid permeation. The results validate that tazarotene can permeate porcine skin and accumulate in articular cartilage in detectable amounts. The detection of tazarotene and tazarotenic acid in both the in vitro permeation studies and the pilot study on porcine joints validate the drug's potential therapeutic use for hand osteoarthritis. This study lays the groundwork for future research, contributing insights into tazarotene's potential for transdermal drug delivery and guiding further exploration in topical retinoid applications.

Background: The aim of this study was to determine the prevalence of preoperative polypharmacy and the incidence of postoperative polypharmacy/hyper-polypharmacy in surgical patients and their association with adverse outcomes., Methods: This was a retrospective, population-based cohort study among patients older than or equal to 18 years undergoing surgery at a university hospital between 2005 and 2018. Patients were categorized based on the number of medications: non-polypharmacy (fewer than 5); polypharmacy (5-9); and hyper-polypharmacy (greater than or equal to 10). The 30-day mortality, prolonged hospitalization (greater than or equal to 10 days), and incidence of readmission were compared between medication-use categories., Results: Among 55 997 patients, the prevalence of preoperative polypharmacy was 32.3 per cent (95 per cent c.i. 33.5 to 34.3) and the prevalence of hyper-polypharmacy was 25.5 per cent (95 per cent c.i. 25.2 to 25.9). Thirty-day mortality was higher for patients exposed to preoperative hyper-polypharmacy (2.3 per cent) and preoperative polypharmacy (0.8 per cent) compared with those exposed to non-polypharmacy (0.6 per cent) (P < 0.001). The hazards ratio (HR) of long-term mortality was higher for patients exposed to hyper-polypharmacy (HR 1.32 (95 per cent c.i. 1.25 to 1.40)) and polypharmacy (HR 1.07 (95 per cent c.i. 1.01 to 1.14)) after adjustment for patient and procedural variables. The incidence of longer hospitalization (greater than or equal to 10 days) was higher for hyper-polypharmacy (11.3 per cent) and polypharmacy (6.3 per cent) compared with non-polypharmacy (4.1 per cent) (P < 0.001). The 30-day incidence of readmission was higher for patients exposed to hyper-polypharmacy (10.2 per cent) compared with polypharmacy (6.1 per cent) and non-polypharmacy (4.8 per cent) (P < 0.001). Among patients not exposed to polypharmacy, the incidence of new postoperative polypharmacy/hyper-polypharmacy was 33.4 per cent (95 per cent c.i. 32.8 to 34.1), and, for patients exposed to preoperative polypharmacy, the incidence of postoperative hyper-polypharmacy was 16.3 per cent (95 per cent c.i. 16.0 to 16.7)., Conclusion: Preoperative polypharmacy and new postoperative polypharmacy/hyper-polypharmacy are common and associated with adverse outcomes. This highlights the need for increased emphasis on optimizing medication usage throughout the perioperative interval., Registration Number: NCT04805151 (http://clinicaltrials.gov)., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Falsely labelled, falsified (counterfeit) medicines (FFCm's) are produced or distributed illegally and can harm patients. Although the occurrence of FFCm's is increasing in Europe, harm is rarely reported. The European Directorate for the Quality of Medicines & Health-Care (EDQM) has therefore coordinated the development and validation of a screening tool., Methods: The tool consists of a questionnaire referring to a watch-list of FFCm's identified in Europe, including symptoms of their use and individual risk factors, and a scoring form. To refine the questionnaire and reference method, a pilot-study was performed in 105 self-reported users of watch-list medicines. Subsequently, the tool was validated under "real-life conditions" in 371 patients in 5 ambulatory and in-patient care sites ("sub-studies"). The physicians participating in the study scored the patients and classified their risk of harm as "unlikely" or "probable" (cut-off level: presence of ≥2 of 5 risk factors). They assessed all medical records retrospectively (independent reference method) to validate the risk classification and documented their perception of the tool's value., Results: In 3 ambulatory care sites (180 patients), the tool correctly classified 5 patients as harmed by FFCm's. The positive and negative likelihood ratios (LR+/LR-) and the discrimination power were calculated for two cut-off levels: a) 1 site (50 patients): presence of two risk factors (at 10% estimated health care system contamination with FFCm's): LR + 4.9/LR-0, post-test probability: 35%; b) 2 sites (130 patients): presence of three risk factors (at 5% estimated prevalence of use of non-prescribed medicines (FFCm's) by certain risk groups): LR + 9.7/LR-0, post-test probability: 33%. In 2 in-patient care sites (191 patients), no patient was confirmed as harmed by FFCm's. The physicians perceived the tool as valuable for finding harm, and as an information source regarding risk factors., Conclusions: This "decision aid" is a systematic tool which helps find in medical practice patients harmed by FFCm's. This study supports its value in ambulatory care in regions with health care system contamination and in certain risk groups. The establishment of systematic communication between authorities and the medical community concerning FFCm's, current patterns of use and case reports may sustain positive public health impacts.