1,721,017 research outputs found

    Antidepressant use in the elderly: The role of pharmacodynamics and pharmacokinetics in drug safety

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    Introduction: Antidepressants (ADs) are widely used among elderly persons, making AD-related safety an important issue.Areas covered: This review highlights safety considerations related to AD use including risks associated with inappropriate and off-label use. The age-related pharmacokinetic and pharmacodynamic changes underlying safety concerns connected to ADs are outlined. Drug-drug interactions as a cause of AD-related adverse drug reactions (ADRs) are also discussed. We reviewed scientific evidence concerning three important safety outcomes related to ADs in elderly persons: cardiac arrhythmias, hyponatraemia and falls/fractures.Expert opinion: Several AD-related ADRs in elderly people are likely to be preventable. Current evidence suggests that selective serotonin re-uptake inhibitors (SSRIs) are best avoided particularly in persons with kidney disease due to the risk of hyponatraemia. The use of tricyclic antidepressants (TCAs) should be limited in the elderly due to anticholinergic adverse effects. TCAs should also be avoided in elderly persons at high risk of cardiovascular events due to a risk of cardiac arrhythmia. Emerging evidence suggests that SSRIs also have arrhythmogenic potential. Both TCAs and SSRIs should be used cautiously in elderly persons at risk of falls. Future research in this area should aim to investigate the lowest effective dose of AD possible, the relationship between AD dose and adverse effects, and which elderly subgroups are most prone to develop severe ADRs

    Measuring frailty in population-based healthcare databases: multi-dimensional prognostic indices for the improvement of geriatric care

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    The prognostic evaluation of geriatric patients is critical in helping clinicians to weigh the risks versus the benefits of available therapeutic options. Frailty contributes significantly to the risk of mortality in older patients and is already known to have implications on the outcome of treatment in a clinical context. The multi-dimensional prognostic index (MPI) is a prognostic tool based on a comprehensive geriatric assessment and includes detailed information on patient cognition, functionality, disease and drug burden. The value of the MPI in predicting mortality has already been shown in hospital and community settings but never in a population- based healthcare database setting. One of the aims of the ongoing EU-funded MPI_Age project is to improve our understanding of how geriatric frailty data can be identified in healthcare databases and whether this can be used to predict serious adverse events associated with pharmacotherapy. Our findings suggest that data on functionality in elderly patients is poorly registered in The Health Improvement Network (THIN), a UK nationwide general practice database, and only few of the functionality domains could be used in a population-based analysis. The most commonly registered functionality information was related to mobility, dressing, accommodation and cognition. Our results suggest that some of these functionality domains are predictive of short- and long-term mortality in community-dwelling patients. This may have implications in observational research where frailty is an unmeasured confounder

    Challenges for Drug Repurposing in the COVID-19 Pandemic Era

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    The coronavirus disease (COVID-19) pandemic has affected an estimated 16 million persons and caused 0.6 million deaths worldwide by September 2020. The pandemic has led to a rush to repurpose existing drugs, although the underlying evidence base is of variable quality. The improving knowledge of the virology and clinical presentation of COVID-19 is leading to a broadening pool of potential pharmacological targets. The aim of this review is to describe regulatory and pharmacological aspects of drug repurposing and to identify drugs proposed for repurposing in COVID-19 based on registered clinical trials, discussing the evidence to support their use in the treatment of this disease. The challenges of the correct interpretation of existing pre-clinical/clinical evidence as well as the generation of new evidence concerning drug repurposing in COVID-19 will also be discussed

    Traceability of Pediatric Antibiotic Purchasing Pathways in Italy: A Nationwide Real-World Drug Utilization Analysis

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    Purpose The aim of the present study was to describe the purchasing patterns of a set of antibiotics used exclusively in an out-patient pediatric setting in Italy using the Farma360 wholesale drug database (IQVIA Solutions Italy), identifying the proportion of medications which are not captured by Italian National Health Service (NHS) pharmacy claims databases and examining the implications of such findings from a public health and pharmaceutical policy perspective. Methods Using a systematic approach, sixty-six antibiotic pediatric formulations were selected for the 5 most commonly used antibiotics in Italy in children and adolescents: amoxicillin in combination with clavulanic acid, amoxicillin, azithromycin, clarithromycin and cefixime. The Farma360 wholesale drug purchasing database was used to identify the yearly proportion of antibiotics not purchased based on NHS reimbursement in primary care from 2015-2017 at the national level. The relationship between product cost and purchase outside the NHS was assessed by a scatterplot. All analyses were stratified by geographic area: Northwest, Northeast, Central and Southern Italy. Results The proportion of antibiotics not reimbursed by the NHS increased nationally from 24% in 2015 to 29% in 2017. The antibiotic with the highest proportion of purchases outside the NHS was amoxicillin, with almost two-thirds of all amoxicillin purchases in Southern Italy being made in this way in 2017. The relationship between antibiotic price and antibiotic purchase outside the NHS was almost linear for many geographic areas. Conclusions This study showed that a large proportion of antibiotics with a pediatric formulation is purchased outside the NHS drug purchasing pathway, especially in Southern Italy, indicating that it is not possible to fully monitor drug utilization, including appropriateness, for these antibiotics. A better strategy is needed to improve drug utilization monitoring, such as better data collection or data linkage

    Azithromycin in COVID-19 Patients: Pharmacological Mechanism, Clinical Evidence and Prescribing Guidelines

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    The global COVID-19 pandemic has led to a race to find medications that can improve the prognosis of the disease. Azithromycin, in association with hydroxychloroquine or chloroquine, has been proposed as one such medication. The aim of this review is to describe the pharmacological mechanism, clinical evidence and prescribing guidelines concerning azithromycin in COVID-19 patients. There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition is not based on results from COVID-19 patients specifically. Therefore, this antibacterial should be considered only as empirical treatment of community-acquired pneumonia (CAP), although not all current treatment guidelines are in agreement. After the initial expectations raised by a small trial, more recent evidence has raised serious safety concerns on the use of hydroxychloroquine or chloroquine with azithromycin to treat COVID-19 patients, as all these drugs have arrhythmogenic potential. The World Health Organization has not made recommendations suggesting the use of azithromycin with hydroxychloroquine or chloroquine as treatment for COVID-19, but some national organisations have taken a different position, recommending this as first-line treatment. Several scientific societies, including the American College of Cardiology, have cautioned about the risks of this treatment in view of the lack of evidence concerning its benefits
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