Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe

Pharmaceutical preparations are medicines that the pharmacist makes for the special needs of the patients that the pharmaceutical industry cannot comply for economic and logistic reasons. Pharmacy compounding is still an important component of pharmacy practice and a valuable therapeutical service that is an integrant part of the modern health care system, but its legislation is not harmonized among European and US countries.In 2011 the Committee of Ministers of the Council of Europe has adopted a Resolution on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. Aim of this resolution is to harmonize quality assurance and standards for pharmacy-made medicinal products among European countries and to pass the gap in quality assurance and standards between preparation in pharmacies and medicines prepared by the pharmaceutical industry. This article will analyze the actual rules and technical norms that regulate compounding activity and the expectations resultants from the new European and US laws

Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability

Glycemic variability (GV) is common in preterm infants. In the premature population, GV is a risk factor for morbidity and mortality. Both hypo- and hyperglycemia can impair neurodevelopment. We investigated the impact of continuous versus intermittent tube enteral feeding on GV. In our prospective observational study, 20 preterm infants with a gestational age ≤ 34 weeks at either continuous or intermittent bolus full enteral feeding. For five days, continuous glucose monitoring (CGM) was utilized, which was achieved through the subcutaneous insertion of a sensor. A total of 27,532 measurements of blood glucose were taken. The mean amplitude of glycemic excursions did not differ between the two cohorts statistically. Continuous feeding resulted in higher positive values, increasing the risk of hypo- and hyperglycemia. Subjects who were small for their gestational age had a higher standard deviation during continuous feeding (p = 0.001). Data suggest that intermittent bolus nutrition is better for glycemic control than continuous nutrition. Nutritional management optimization of preterm infants appears to be critical for long-term health. In the future, CGM may provide a better understanding of the optimal glucose targets for various clinical conditions, allowing for a more personalized approach to management

Data on the stability of darunavir/cobicistat suspension after tablet manipulation

The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients\u2019 need. In this situation, it is urgent to provide data and guidance to support hospital pharmacists and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week

Fixed Versus Free Combinations of Antihypertensive Drugs: Analyses Of Real-World Data Of Persistence With Therapy In Italy

Purpose: To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. Patients and methods: In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: \u201ccontinuer\u201d, \u201cdiscontinuer\u201d \u201cswitching\u201d or \u201cadd-on\u201d. A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists\u2019 visits, diagnostic procedures and pharmacologic therapies. Results: Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was 3c\u20ac95.3 (IQR, 144.9). The monotherapy cost was \u20ac88 per patient (IQR, 132.9), and that for combination therapy was \u20ac151\ub1148.3. The median cost/patient with a fixed combination was lower than that for a free combination (\u20ac98.4 (IQR, 155.3) and \u20ac154.9 (IQR, 182.6), respectively). Conclusion: The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy

Rethinking the neonatal transport ground ambulance

Objectives: This article describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service (NETS). To date, the European Community rules specify requirements for the design, testing, performance, and equipping of road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. Methods: The project consisted of electric and gas supply planning, interior design taking into account ergonomic and occupant protection principles, both during travel and during medical care performances. Results: A detailed project is presented. Main differences between European Type C ambulance and the new proposed Type D neonatal ground ambulance are the presence on board of air compressed cylinder, iNO cylinders and delivery system, phototheraphy, shock adsorbing stretcher support, cooling device, patient's placenta (refrigeration box), and transcutaneous gas analyzer. Conclusion: The European Community rules specify requirements for road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. This study describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service. This study demonstrated that it is not possible simply to adapt the currently dedicated ambulance for mobile intensive care and resuscitation services (actual type C European Community) in a modern dedicated NETS ambulance; it is of paramount importance suggesting to European Community to introduce a further ambulance type, to be identified type D, strictly reserved to neonatal transport activities

Early Pain Exposure Influences Functional Brain Connectivity in Very Preterm Neonates

Background: Early exposure to nociceptive events may cause brain structural alterations in preterm neonates, with long-lasting consequences on neurodevelopmental outcome. Little is known on the extent to which early pain may affect brain connectivity. We aim to evaluate brain functional connectivity changes in preterm neonate that underwent multiple invasive procedures during the postnatal period, and to correlate them with the neurodevelopmental outcome at 24 months. Methods: In this prospective case-control study, we collected information about exposure to painful events during the early postnatal period and resting-state BOLD-fMRI data at term equivalent age from two groups of preterm neonate: 33 subjected to painful procedures during the neonatal intensive care (mean gestational age 27.9 \ub1 1.8 weeks) and 13 who did not require invasive procedures (average gestational age 31.2 \ub1 2.1 weeks). A data-driven principal-component-based multivariate pattern analysis (MVPA) was used to investigate the effect of early pain exposure on brain functional connectivity, and the relationship between connectivity changes and neurodevelopmental outcome at 24 months, assessed with Griffiths, Developmental Scale-Revised: 0\u20132. Results: Early pain was associated with decreased functional connectivity between thalami and bilateral somatosensory cortex, and between the right insular cortex and ipsilateral amygdala and hippocampal regions, with a more evident effect in preterm neonate undergoing more invasive procedures. Functional connectivity of the right thalamocortical pathway was related to neuromotor outcome at 24 months (P = 0.003). Conclusion: Early exposure to pain is associated with abnormal functional connectivity of developing networks involved in the modulation of noxious stimuli in preterm neonate, contributing to the neurodevelopmental consequence of preterm birth

The strategic relevance of manufacturing technology : an overall quality concept to promote innovation preventing drug shortage

Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation

Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima

<p>Abstract</p> <p>Background</p> <p>The neuroinflammatory process plays a central role in the initiation and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and involves the activation of brain microglial cells. During the neuroinflammatory process, microglial cells release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), Reactive oxygen species (ROS) and nitric oxide (NO). In the present study, extracts from 66 different desert plants were tested for their effect on lipopolysaccharide (LPS) - induced production of NO by primary microglial cells. The extract of <it>Achillea fragrantissima </it>(<it>Af</it>)<it/>, which is a desert plant that has been used for many years in traditional medicine for the treatment of various diseases, was the most efficient extract, and was further studied for additional anti-neuroinflammatory effects in these cells.</p> <p>Methods</p> <p>In the present study, the ethanolic extract prepared from <it>Af </it>was tested for its anti-inflammatory effects on lipopolysaccharide (LPS)-activated primary cultures of brain microglial cells. The levels of the proinflammatory cytokines interleukin1β (IL-1β) and tumor necrosis factor-α (TNFα) secreted by the cells were determined by reverse transcriptase-PCR and Enzyme-linked immunosorbent assay (ELISA), respectively. NO levels secreted by the activate cells were measured using Griess reagent, ROS levels were measured by 2'7'-dichlorofluorescein diacetate (DCF-DA), MMP-9 activity was measured using gel zymography, and the protein levels of the proinflammatory enzymes cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS) were measured by Western blot analysis. Cell viability was assessed using Lactate dehydrogenase (LDH) activity in the media conditioned by the cells or by the crystal violet cell staining.</p> <p>Results</p> <p>We have found that out of the 66 desert plants tested, the extract of <it>Af </it>was the most efficient extract and inhibited ~70% of the NO produced by the LPS-activated microglial cells, without affecting cell viability. In addition, this extract inhibited the LPS - elicited expression of the proinflammatory mediators IL-1β, TNFα, MMP-9, COX-2 and iNOS in these cells.</p> <p>Conclusions</p> <p>Thus, phytochemicals present in the <it>Af </it>extract could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.</p