Medicated foams and film forming dosage forms as tools to improve the thermodynamic activity of drugs to be administered through the skin

Medicated foams and film forming systems are dosage forms formulated to undergo to a controlled metamorphosis when applied on the skin. Indeed, due to the presence of propellant or a particular air-spray foam pump, a liquid can generate a foam when applied on the stratum corneum, or a liquid or conventional dosage form can form on the skin a continuous film as a consequence of the solvent evaporation. Thanks to these controlled modifications, the drug thermodynamic activity increases favoring the skin penetration and, therefore, the bioavailability with respect to conventional semi-solid and liquid dosage forms. Furthermore, the available clinical data also evidence that these dosage forms improve the patient's compliance. The main formulative aspects of medicated foams and film forming systems are reviewed with the aim to underline the possible advantages in terms of biopharmaceutical performances and patient's adherence

Design of pressure-sensitive adhesive suitable for the preparation of transdermal patches by hot-melt printing

This work aimed to design low-melting pressure sensitive adhesives and to demonstrate the feasibility of the preparation of (trans)dermal patches by hot-melt ram extrusion printing. This approach allows defining both the geometry of (trans)dermal patch and the drug strength easily according to patient needs. The preparation steps are the mixing of a poly-ammonium methacrylate polymer (i.e. Eudragit RL and RS) with a suitable amount of plasticizer (triacetin or tributyl citrate) and drug (ketoprofen or nicotine), the melting in the ram extruder, and the printing on the backing layer foil. The formulations were characterized in terms of rheological and adhesive properties, in vitro drug release and skin permeation profiles. The (trans)dermal patches made of Eudragit RL or Eudragit RS plasticized with the 40% triacetin could be printed at 90 \ub0C giving formulations with suitable adhesive properties and without cold flow after 1 month of storage at 40 \ub0C. Furthermore, the overall results showed that the performances of printed (trans)dermal patches overlapped those made by solvent casting, suggesting that the proposed solvent-free technology can be useful to treat cutaneous pathologies when the availability of (trans)dermal patches with size and shape that perfectly fit with the skin area affected by the disease improves the safety of the pharmacological treatment

L’influenza dell’attaccamento e della sensibilità diadica genitorialesullo sviluppo psicomotorio del bambino nato pretermine

Lo scopo di questa ricerca è studiare i precursori dell’attaccamento e la sensibilità diadica genitoriale nelle famiglie con bambino nato pretermine. Sono state considerate 110 famiglie delle quali 55 con figli nati pretermine ( peso alla nascita < 1500 gr.) per un totale di 330 soggetti valutati durante i primi sei mesi di età corretta del bambino. Le diadi madre-bambino e padre-bambino sono state sottoposte al CARE-Index, una procedura videoregistrata per la valutazione dei precursori dell’attaccamento; ad entrambi i genitori sono stati somministrati CES-D, per la valutazione della depressione e STAI Y-2, per la valutazione dell’ansia di tratto. Lo sviluppo psicomotorio dei neonati è stato valutato tramite le scale Bayley. Rispetto ai controlli, nelle madri dei bambini pretermine sono stati evidenziati bassi punteggi di Sensibilità Diadica al CARE-Index (p=.025) ed elevati livelli di ansia (p=.026). Nei padri sono stati riscontrati bassi punteggi di Sensibilità Diadica (p=.004) e alti livelli di sintomi depressivi (p=.003). Nelle famiglie pretermine i precursori dell’attaccamento sono più frequentemente di tipo insicuro nelle madri (p=.000) e nei padri (p=.000), mentre nei neonati solo nell’interazione con la madre (p=012). Questi fattori sono risultati associati a minori punteggi alle scale Bayley (p=.000). Nelle madri dei neonati pretermine si riscontrano frequenti difficoltà con la famiglia di origine, nei padri una percezione negativa del proprio bambino e una maggiore insoddisfazione per l’assistenza ricevuta. Questi risultati evidenziano che il 40% delle madri e il 75% dei padri dei bambini nati pretermine rientra nella fascia ad alto rischio del CARE-Index (che richiede un trattamento psicologico e/o farmacologico). In tali casi, la scarsa sensibilità diadica, i precursori di attaccamento insicuro e le difficoltà psicologiche dei genitori sembrano influenzare lo sviluppo psicomotorio del bambino

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

Antibiotic De-Escalation in Emergency General Surgery

Background. Antibiotic treatment in emergency general surgery (EGS) is a major challenge for surgeons, and a multidisciplinary approach is necessary in order to improve outcomes. Intra-abdominal infections are at high risk of increased morbidity and mortality, and prolonged hospitalization. An increase in multi-drug resistance bacterial infections and a tendency to an antibiotic overuse has been described in surgical settings. In this clinical scenario, antibiotic de-escalation (ADE) is emerging as a strategy to improve the management of antibiotic therapy. The objective of this article is to summarize the available evidence, current strategies and unsolved problems for the optimization of ADE in EGS. Methods. A literature search was performed on PubMed and Cochrane using “de-escalation”, “antibiotic therapy” and “antibiotic treatment” as research terms. Results. There is no universally accepted definition for ADE. Current evidence shows that ADE is a feasible strategy in the EGS setting, with the ability to optimize antibiotic use, to reduce hospitalization and health care costs, without compromising clinical outcome. Many studies focus on Intensive Care Unit patients, and a call for further studies is required in the EGS community. Current guidelines already recommend ADE when surgery for uncomplicated appendicitis and cholecystitis reaches a complete source control. Conclusions. ADE in an effective and feasible strategy in EGS patients, in order to optimize antibiotic management without compromising clinical outcomes. A collaborative effort between surgeons, intensivists and infectious disease specialists is mandatory. There is a strong need for further studies selectively focusing in the EGS ward setting

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

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

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