Pharmacological interventions in human aging.

Pharmacological interventions are emerging as potential avenues of alleviating age-related disease. However, the knowledge of ongoing clinical trials as they relate to aging and pharmacological interventions is dispersed across a variety of mediums. In this review we summarize 136 age-related clinical trials that have been completed or are ongoing. Furthermore, we establish a database that describe the trials (AgingDB, www.agingdb.com) keeping track of the previous and ongoing clinical trials, alongside their outcomes. The aim of this review and database is to give people the ability to easily query for their trial of interest and stay up to date on the latest results. In sum, herein we give an overview of the current pharmacological strategies that have been applied to target human aging.

Applying the behavior change wheel to design de-implementation strategies to reduce low-value statin prescription in primary prevention of cardiovascular disease in primary care.

Introduction: A substantial proportion of individuals with low cardiovascular risk receive inappropriate statin prescription for primary prevention of cardiovascular disease (CVD) instead of the evidence-based recommendations to promote healthy lifestyle behaviors. This study reports on the structured process performed to design targeted de-implementation strategies to reduce inappropriate prescription of statins and to increase healthy lifestyle promotion in low cardiovascular risk patients in Primary Care (PC). Methods: A formative study was conducted based on the Theoretical Domains Framework and the Behavior Change Wheel (BCW). It comprised semi-structured interviews with PC professionals to define the problem in behavioral terms; focus groups with Family Physicians and patients to identify the determinants (barriers and facilitators) of inappropriate statin prescription and of healthy lifestyle promotion practice; mapping of behavioral change interventions operationalized as de-implementation strategies for addressing identified determinants; and consensus techniques for prioritization of strategies based on perceived effectiveness, feasibility and acceptability. Results: Identified key determinants of statin prescription and healthy lifestyle promotion were: the lack of time and clinical inertia, external resources, patients' preferences and characteristics, limitation of available clinical tools and guidelines, social pressures, fears about negative consequences of not treating, and lack of skills and training of professionals. Fourteen potential de-implementation strategies were mapped to the identified determinants and the following were prioritized: 1) non-reflective decision assistance strategies based on reminders and decision support tools for helping clinical decision-making; 2) decision information strategies based on the principles of knowledge dissemination (e.g., corporative diffusion of evidence-based Clinical Practice Guidelines and Pathways for CVD primary prevention); 3) reflective decision-making restructuring strategies (i.e., audit and feedback provided along with intention formation interventions). Conclusions: This study supports the usefulness of the BCW to guide the design and development of de-implementation strategies targeting the determinants of clinicians' decision-making processes to favor the abandonment of low-value practices and the uptake of those recommended for CVD primary prevention in low-risk patients. Further research to evaluate the feasibility and effectiveness of selected strategies is warranted. Clinical trial registration: Sanchez A. De-implementation of Low-value Pharmacological Prescriptions (De-imFAR). ClinicalTrials.gov, Identifier: NCT04022850. Registered July 17, 2019. In: ClinicalTrials.gov. Bethesda (MD): U.S. National Library of Medicine (NLM). Available from: https://www.clinicaltrials.gov/ct2/show/NCT04022850.

Addressing low-value pharmacological prescribing in primary prevention of CVD through a structured evidence-based and theory-informed process for the design and testing of de-implementation strategies: the DE-imFAR study.

BACKGROUND: De-implementation or abandonment of ineffective or low-value healthcare is becoming a priority research field globally due to the growing empirical evidence of the high prevalence of such care and its impact in terms of patient safety and social inefficiency. Little is known, however, about the factors, barriers, and facilitators involved or about interventions that are effective in promoting and accelerating the de-implementation of low-value healthcare. The De-imFAR study seeks to carry out a structured, evidence-based, and theory-informed process involving the main stakeholders (clinicians, managers, patients, and researchers) for the design, deployment, and assessment of de-implementation strategies for reducing low-value pharmacological prescribing. METHODS: A phase I formative study using a systematic and comprehensive framework based on theory and evidence for the design of implementation strategies-specifically, the Behavior Change Wheel (BCW)-will be conducted to design and model de-implementation strategies to favor reductions in low-value pharmacological prescribing of statins in primary prevention of cardiovascular disease (CVD) by main stakeholders (clinicians, managers, patients, and researchers) in a collegiate way. Subsequently, a phase II comparative hybrid trial will be conducted to assess the feasibility and potential effectiveness of at least one active de-implementation strategy to reduce low-value pharmacological prescribing of statins in primary prevention of CVD compared to the usual procedures for dissemination of clinical practice guidelines ("what-not-to-do" recommendations). A mixed-methods evaluation will be used: quantitative for the results of the implementation at the professional level (e.g., adoption, reach and implementation or execution of the recommended clinical practice); and qualitative to determine the feasibility and perceived impact of the de-implementation strategies from the clinicians' perspective, and patients' experiences related to the clinical care received. DISCUSSION: The DE-imFAR study aims to generate valid scientific knowledge about the design and development of de-implementation strategies using theory- and evidence-based methodologies suggested by implementation science. It will explore the effectiveness of these strategies and their acceptability among clinicians, policymakers, and patients. Its ultimate goal is to maximize the quality and efficiency of our health system by abandoning low-value pharmacological prescribing. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04022850. Registered 17 July 2019.

Physicochemical Compatibility of Amiodarone with Parenteral Nutrition.

BACKGROUND: Y-site administration of total parenteral nutrition (TPN) and drugs is frequently required in the intensive care setting. Amiodarone is commonly administered by continuous intravenous infusion and subject to be co-administered via a Y-site with TPN. The aim of this study is to determine the physicochemical stability of amiodarone Y-site administered with TPN. METHODS: Two standard TPN and 2 amiodarone solutions were designed. The 2 TPN differed in the lipid source (Lipofundin MCT/LCT® 20% or SMOFlipid® 20%). The 2 amiodarone solutions were prepared at different concentrations (900 mg and 1200 mg in 250 mL of dextrose 5% in water). Each TPN and amiodarone solutions ran at a rate that simulated a 24-hour Y-site infusion to obtain different admixture samples. Each sample was then visually examined and further tested to determine the mean lipid droplet size distribution by dynamic light scattering and amiodarone concentrations by HPLC. RESULTS: No alterations were detected by visual inspection. Average droplet size remained below 500 nm (252.5 ± 5.9 nm for Lipofundin MCT/LCT® TPN and 327.7 ± 14.4 nm for SMOFlipid® TPN). For the samples obtained after running 900 mg and 1200 mg amiodarone solutions with TPN, the concentrations observed at 24 hours were 0.4491 ± 0.0111 mg/mL and 0.5773 ± 0.0214 mg/mL, respectively. These results represent approximately 100% of the zero-time concentrations and are within ±15% of the predicted values. No degradation products were observed in the chromatograms. CONCLUSION: Amiodarone is physicochemically compatible with standard TPN via a Y-site administration at the tested amiodarone concentrations.

Insuficiencia cardíaca secundaria a tratamiento con itraconazol / Heart failure induced by itraconazole

Introducción y objetivo: Itraconazol es un antifúngico imidazólico para el tratamiento de la aspergilosis. La evidencia que respalda la asociación entre itraconazol y el desarrollo de insuficiencia cardíaca congestiva (ICC) es limitada y se basa en los casos notificados poscomercialización del fármaco. Caso clínico: Presentamos el caso de un varón de 76 años, hipertenso, con EPOC GOLD D, que presenta un inicio de insuficiencia cardíaca tras la introducción de tratamiento con itraconazol. Tras la retirada del fármaco y tratamiento diurético muestra resolución completa del cuadro clínico. Tras utilizar varios algoritmos validados sobre causalidad de efectos adversos se concluyó como probable la asociación entre itraconazol y el desarrollo de ICC en este caso. Conclusiones: La asociación entre la administración de itraconazol y el desarrollo de ICC es una relación causal difícil de demostrar. Son necesarios estudios observacionales dirigidos a evaluar tal asociación. No obstante, con la evidencia disponible debemos considerar la posibilidad de dicho efecto adverso e incluso valorar la contraindicación en pacientes con antecedentes de cardiopatía estructural (AU)

Introduction and objective: Itraconazole is an antifungal imidazole used for the treatment of aspergillosis. Evidence supporting the association between itraconazole and the onset of congestive heart failure (CHF) is limited and is based on cases reported after drug market release. Case report: We report the case of a 76-year-old man with hypertension and COPD GOLD D who experienced heart failure after receiving a new line of treatment with itraconazole. The patient’s symptoms resolved completely after the drug’s withdrawal and initiation of treatment with diuretic therapy. Using validated algorithms, we concluded that there was a probable association between itraconazole and the onset of CHF. Conclusions: The association between the administration of itraconazole and the onset of CHF is difficult to prove. Further observational studies are needed to assess this association. However, based on the available evidence, we should consider this possible adverse effect and even contraindicate this treatment in patients with a structural heart disease (AU)

Heart failure induced by itraconazole. / Insuficiencia cardíaca secundaria a tratamiento con itraconazol.

INTRODUCTION AND OBJECTIVE: Itraconazole is an antifungal imidazole used for the treatment of aspergillosis. Evidence supporting the association between itraconazole and the onset of congestive heart failure (CHF) is limited and is based on cases reported after drug market release. CASE REPORT: We report the case of a 76-year-old man with hypertension and COPD GOLD D who experienced heart failure after receiving a new line of treatment with itraconazole. The patient's symptoms resolved completely after the drug's withdrawal and initiation of treatment with diuretic therapy. Using validated algorithms, we concluded that there was a probable association between itraconazole and the onset of CHF. CONCLUSIONS: The association between the administration of itraconazole and the onset of CHF is difficult to prove. Further observational studies are needed to assess this association. However, based on the available evidence, we should consider this possible adverse effect and even contraindicate this treatment in patients with a structural heart disease.