Management of behavioural and psychological symptoms in dementia : NICE guidelines and evidence-based decision-making

Dementia is an age-related progressive syndrome that often presents with psychiatric symptoms such as hallucinations, aggression and agitation. The management of such symptoms in dementia is particularly important when it puts the patients themselves and their carers at risk. The NICE guidance for pharmacologically managing psychiatric symptoms in dementia and the evidence base is summarised with particular focus on antipsychotic drug use. Alternative approaches to psychiatric symptoms in dementia are briefly discussed as a substitute for antipsychotic use.peer-reviewe

New safety information on Azithromycin

In the last few years the scientific community was debating the safety of the widely used macrolide antibiotic, azithromycin, which is commonly prescribed for respiratory and urinary tract infections. Previously published observational studies examined the risk of cardiovascular outcomes with azithromycin use, but these studies had conflicting results. The first such study to be published, a cohort study using U.S. Medicaid data, found an increased risk of cardiovascular death with azithromycin use. This led the Food and Drug Association to issue a warning on the safety of azithromycin use, although the European Medicines Agency did not take a position on this issue. Subsequent studies, both in the U.S. and in Europe did not always observe a risk of cardiovascular adverse events. This was likely due to several factors. Some studies investigated the link between cardiovascular death and azithromycin use. However, cardiovascular death can be considered a rather ambiguous outcome .given that the concern with aZithromycin use should be ventricular arrhythmia specifically, based on the effect of macrolides on QT- interval prolongation. Cardiovascular death may be due to conditions unrelated to ventricular arrhythmia. It is therefore possible that the cardiovascular impact of azithromycin is over-estimated by using this general clinical outcome. Another important factor leading to variation among the published studies is the diversity in the underlying study populations. For example, a study conducted among persons with a lower socioeconomic status such as Medicaid beneficiaries may show a comparatively higher cardiovascular risk than a European population.peer-reviewe

Challenges for Drug Repurposing in the COVID-19 Pandemic Era

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

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

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

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

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

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

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

Potential effects of vaccinations on the prevention of COVID-19: rationale, clinical evidence, risks, and public health considerations

IntroductionCoronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has quickly spread around the world. Areas coveredThis review will discuss the available immunologic and clinical evidence to support the benefit of the influenza, pneumococcal, and tuberculosis vaccines in the context of COVID-19 as well as to provide an overview on the COVID-19-specific vaccines that are in the development pipeline. In addition, implications for vaccination strategies from a public health perspective will be discussed. Expert opinionSome vaccines are being considered for their potentially beneficial role in preventing or improving the prognosis of COVID-19: influenza, pneumococcal and tuberculosis vaccines. These vaccines may have either direct effect on COVID-19 via different types of immune responses or indirect effects by reducing the burden of viral and bacterial respiratory diseases on individual patients and national healthcare system and by facilitating differential diagnoses with other viral/bacterial respiratory disease. On the other hand, a large number of candidate vaccines against SARS-CoV-2 are currently in the pipeline and undergoing phase I, II, and III clinical studies. As SARS-CoV-2 vaccines are expected to be marketed through accelerated regulatory pathways, vaccinovigilance as well as planning of a successful vaccination campaign will play a major role in protecting public health

Healthcare Database Networks for Drug Regulatory Policies: International Workshop on the Canadian, US and Spanish Experience and Future Steps for Italy

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Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy

Patients enrolled into pivotal randomized controlled trials (RCTs) may differ substantially from those treated in a real-world (RW) setting, which may result in a different benefit\u2013risk profile. The aim of the study was to assess the external validity of pivotal RCT findings concerning direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (NVAF) by comparing patients recruited in RCTs to those treated with DOACs registered in a southern Italian local health unit (LHU) in the years 2013\u20132017. The Palermo LHU claims database was used to describe the baseline characteristics of incident DOAC users (washout > 1 year) with NVAF compared with those of enrolled patients in DOAC pivotal RCTs. In the RW, DOAC treatment discontinuation was calculated during the follow-up and compared with DOAC treatment discontinuation of enrolled patients in DOAC pivotal RCTs. Rates of effectiveness and safety outcomes during the follow-up were calculated in an unmatched and in a simulated RCT population, by matching individual incidental RW and RCT DOAC users (excluding edoxaban users) on age, sex, and CHADS2 score. Overall, 42,336 and 7092 incident DOAC users with NVAF were identified from pivotal RCTs and from the RW setting, respectively. In RCTs, DOAC use was more common among males (62.6%) compared with an almost equal sex distribution in the RW. RCT patients were younger (mean age \ub1 standard deviation: 70.7 \ub1 9.2 years) than RW patients (76.0 \ub1 8.6 years). Compared with RCTs, a higher proportion of RW dabigatran users (30.4% vs. 19.6%) and a lower proportion of RW apixaban (15.9% vs. 25.3%) and rivaroxaban (20.4% vs. 23.7%) users discontinued the treatment during the follow-up (p-value < 0.001). The rate of ischemic stroke was lower in RW high-dose dabigatran users (unmatched/-matched population: 0.40\u20130.11% per year) than in the Randomized Evaluation of Long- Term Anticoagulation Therapy (RE-LY) population (0.93% per year). Major bleeding rates were lower in RW users than in RCT users. In conclusion, except for dabigatran, a lower proportion of DOAC discontinuers was observed in the real-world than in pivotal RCT settings. This study provides reassurance to practicing physicians that DOAC use appears to be effective in stroke prevention and is likely safer in RW patients than in RCT enrolled patients. These results may be related to a lower burden of comorbidities despite more advanced age in the RW population compared to the pivotal RCT population

Effect of an educational program in primary care: the case of lipid control in cardio-cerebrovascular prevention.

Lowering blood cholesterol levels reduces the risk of coronary heart disease. However, the effect of interventions depends on the patients' adherence to treatment. Primary care plays an important role in the detection, treatment and monitoring of disease, therefore different educational programs (EP) have been implemented to improve disease management in general practice. The present study is aimed to assess whether a general practitioner auditing and feedback EP may improve dyslipidaemia management in a primary care setting and to evaluate patients' adherence to prescribed lipid-lowering treatment. The quality of cardiovascular and cerebrovascular disease prevention before and after the implementation of an EP offered to 25 general practitioners (GPs), was evaluated. Clinical and prescription data on patients receiving at least one lipid-lowering treatment was collected. To evaluate the quality of the healthcare service provided, clinical and biochemical outcomes, and drug-utilization, process indicators were set up. Adherence was evaluated before and after the EP as the "Medication Possession Ratio" (MPR). A correlation analysis was carried out to estimate the effect of the MPR in achieving pre-defined clinical end-points. Prescription data for lipid-lowering drugs was collected in a sample of 839 patients. While no differences in the achievement of blood lipid targets were observed, a slight but significant improvement of the MPR was registered after the EP (MPR >0.8=64.2% vs 60.6%, p=0.0426). Moreover, high levels of statin adherence were associated with the achievement of total blood cholesterol target (OR=3.3 for MPR >0.8 vs MPR 0.8 vs MPR <0.5,95% CI: 1.5–7.2). The EP partially improved the defined clinical targets; probably, a more patient-based approach could be more appropriate to achieve the defined target. Further studies are needed to identify how healthcare services can be improved