Effectiveness of a medication adherence management intervention in a community pharmacy setting: a cluster randomised controlled trial

BackgroundNon-adherence to medications continues to be a burden worldwide, with significant negative consequences. Community pharmacist interventions seem to be effective at improving medication adherence. However, more evidence is needed regarding their impact on disease-specific outcomes. The aim was to evaluate the impact of a community pharmacist-led adherence management intervention on adherence and clinical outcomes in patients with hypertension, asthma and chronic obstructive pulmonary disease (COPD).MethodsA 6-month cluster randomised controlled trial was conducted in Spanish community pharmacies. Patients suffering from hypertension, asthma and COPD were recruited. Patients in the intervention group received a medication adherence management intervention and the control group received usual care. The intervention was based on theoretical frameworks for changing patient behaviour. Medication adherence, disease-specific outcomes (Asthma Control Questionnaire (ACQ) scores, Clinical COPD Questionnaire (CCQ) scores and blood pressure levels) and disease control were evaluated. A multilevel regression model was used to analyse the data.ResultsNinety-eight pharmacies and 1186 patients were recruited, with 1038 patients completing the study. Patients receiving the intervention had an OR of 5.12 (95% CI 3.20 to 8.20, pConclusionsA community pharmacist-led medication adherence intervention was effective at improving medication adherence and clinical outcomes in patients suffering from hypertension, asthma and COPD. Future research should explore the implementation of these interventions in routine practice.Trial registration numberACTRN12618000410257

Cost-Utility Analysis of a Medication Adherence Management Service Alongside a Cluster Randomized Control Trial in Community Pharmacy.

Background: It is necessary to determine the cost utility of adherence interventions in chronic diseases due to humanistic and economic burden of non-adherence. Purpose: To evaluate, alongside a cluster-randomized controlled trial, the cost-utility of a pharmacist-led medication adherence management service (MAMS) compared with usual care in community pharmacies. Materials and Methods: The trial was conducted over six months. Patients with treatments for hypertension, asthma or chronic obstructive pulmonary disease (COPD) were included. Patients in the intervention group (IG) received a MAMS based on a brief complex intervention, whilst patients in the control group (CG) received usual care. The cost–utility analysis adopted a health system perspective. Costs related to medications, healthcare resources and adherence intervention were included. The effectiveness was estimated as quality-adjusted life years (QALYs), using a multiple imputation missing data model. The incremental cost–utility ratio (ICUR) was calculated on the total sample of patients. Results: A total of 1186 patients were enrolled (IG: 633; CG: 553). The total intervention cost was estimated to be € 27.33 ± 0.43 per patient for six months. There was no statistically significant difference in total cost of medications and healthcare resources per patient between IG and CG. The values of EQ-5D-5L at 6 months were significantly higher in the IG [IG: 0.881 ± 0.005 vs CG: 0.833 ± 0.006; p = 0.000]. In the base case, the service was more expensive and more effective than usual care, resulting in an ICUR of € 1,494.82/QALY. In the complete case, the service resulted in an ICUR of € 2,086.30/QALY, positioned between the north-east and south-east quadrants of the cost–utility plane. Using a threshold value of € 20,000/QALY gained, there is a 99% probability that the intervention is cost-effective. Conclusion: The medication adherence management service resulted in an improvement in the quality of life of the population with chronic disease, with similar costs compared to usual care. The service is cost-effective

Profibrotic role of inducible heat shock protein 90α isoform in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-β, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.This work was supported by Spanish Ministerio de Economía, Industria y Competitividad, Gobierno de España Grant RTI2018-095214-B-I00, as well as by the Instituto de Formación e Investigación Marqués de Valdecilla IDIVAL (InnVal 17/22; InnVal 20/34), 2020UCI22-PUB-0003 Gobierno de Cantabria (to A.V.V.), SAF2016-75195-R (to J.M.), SAF2017-82905-R (to R.M.), and (NextVal 18/14) to A.P

Investigation of Different Iontophoretic Currents Profiles for Short-Term Applications in Cosmetics

[EN] This study aimed at investigating the effect of electrical current profile upon the iontophoretic transport of (i) ascorbic acid (AA) and (ii) ellagic acid (EA), into porcine skin in vitro, and the impact of the physicochemical properties of both actives on their mechanism of transport when formulated in cosmetic compositions. The experiments were performed using a proprietary iontophoretic device containing a roller to apply the formulation. Three current profiles were tested: (i) galvanic direct current (DC), (ii) square unipolar pulse current (SPC), and (iii) galvanic direct current (DC) + pulse current (PC). The skin samples were collected at different sampling points, extracted and analyzed by HPLC. Results suggested that the DC + PC mode for only 5 min was able to significantly increase the delivery of AA from o/w cosmetic compositions. The use of this current profile might improve the skin penetration of AA due to electromigration and passive diffusion, the latter being facilitated by the physical enhancement method. The SPC mode significantly improved the passage of EA in its neutral form from cosmetic o/w formulations by electroosmosis. Tailoring specific electrical current modes considering the ionization state of active ingredients would allow the design of short and personalized cosmetic treatments that significantly improve the penetration efficiency of the active ingredients and possibly reduce the doses applied.This research was entirely funded by L'Oreal, France.Cázares-Delgadillo, J.; Planard-Luong, L.; Gregoire, S.; Serna-Jiménez, CE.; Singhal, M.; Kalia, YN.; Merino Sanjuán, V.... (2018). Investigation of Different Iontophoretic Currents Profiles for Short-Term Applications in Cosmetics. Pharmaceutics. 10(4). https://doi.org/10.3390/pharmaceutics10040266266104R. Hamad, A.-W., Al-Momani, W. M., Janakat, S., & A. Oran, S. (2009). Bioavailability of Ellagic Acid After Single Dose Administration Using HPLC. Pakistan Journal of Nutrition, 8(10), 1661-1664. doi:10.3923/pjn.2009.1661.1664Kalia, Y. N., Naik, A., Garrison, J., & Guy, R. H. (2004). Iontophoretic drug delivery. Advanced Drug Delivery Reviews, 56(5), 619-658. doi:10.1016/j.addr.2003.10.026Marro, D., Kalia, Y. N., Begoña Delgado‐Charro, M., & Guy, R. H. (2001). Pharmaceutical Research, 18(12), 1701-1708. doi:10.1023/a:1013318412527Sobhi, R. M., & Sobhi, A. M. (2012). A single-blinded comparative study between the use of glycolic acid 70% peel and the use of topical nanosome vitamin C iontophoresis in the treatment of melasma. Journal of Cosmetic Dermatology, 11(1), 65-71. doi:10.1111/j.1473-2165.2011.00599.xHori, Y., Akimoto, R., Hori, A., Kato, K., Chino, D., Matsumoto, S., … Watanabe, Y. (2010). Skin collagen reproduction increased by ascorbic acid derivative iontophoresis by frequent-reversal bipolar electric stimulation. International Journal of Cosmetic Science, 32(3), 234-234. doi:10.1111/j.1468-2494.2010.00577_3.xJunyaprasert, V. B., Singhsa, P., Suksiriworapong, J., & Chantasart, D. (2012). Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. International Journal of Pharmaceutics, 423(2), 303-311. doi:10.1016/j.ijpharm.2011.11.032Maia, A. M., Baby, A. R., Pinto, C. A. S. O., Yasaka, W. J., Suenaga, E., Kaneko, T. M., & Velasco, M. V. R. (2006). Influence of sodium metabisulfite and glutathione on the stability of vitamin C in O/W emulsion and extemporaneous aqueous gel. International Journal of Pharmaceutics, 322(1-2), 130-135. doi:10.1016/j.ijpharm.2006.05.03

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study

Background: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. Objective: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile.Methods: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected.Results: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. Conclusion: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.& COPY; 2023 AEDV. Published by Elsevier Espan & SIM;a, S.L.U.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix

Interdigital cell death is a physiological regression process responsible for sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity of this degenerative process account for the different patterns of interdigital webbing among vertebrate species. Here, we show that Reelin is present in the extracellular matrix of the interdigital mesoderm of chick and mouse embryos during the developmental stages of digit formation. Reelin is a large extracellular glycoprotein which has important functions in the developing nervous system, including neuronal survival; however, the significance of Reelin in other systems has received very little attention. We show that reelin expression becomes intensely downregulated in both the chick and mouse interdigits preceding the establishment of the areas of interdigital cell death. Furthermore, fibroblast growth factors, which are cell survival signals for the interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which are proapototic signals, downregulate its expression in the interdigit. Gene silencing experiments of reelin gene or its intracellular effector Dab-1 confirmed the implication of Reelin signaling as a survival factor for the limb undifferentiated mesoderm. We found that Reelin activates canonical survival pathways in the limb mesoderm involving protein kinase B and focal adhesion kinase. Our findings support that Reelin plays a role in interdigital cell death, and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be involved in this process

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider

The TESLA Technical Design Report Part III: Physics at an e+e- Linear ColliderComment: 192 pages, 131 figures. Some figures have reduced quality. Full quality figures can be obtained from http://tesla.desy.de/tdr. Editors - R.-D. Heuer, D.J. Miller, F. Richard, P.M. Zerwa