Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether melatonin or ramelteon (melatonin agonist) reduce delirium incidence as compared to a placebo in ICU patients. Secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV) and mortality. Estimates are presented as risk ratio (RR) or mean differences (MD) with 95% confidence interval (CI). Nine RCTs were included, six of them reporting delirium incidence. Neither melatonin nor ramelteon reduced delirium incidence (RR 0.76 (0.54, 1.07), p = 0.12; I² = 64%), although a sensitivity analysis conducted adding other four studies showed a reduction in the risk of delirium (RR = 0.67 (95%CI 0.48, 0.92), p = 0.01; I² = 67). Among the secondary outcomes, we found a trend towards a reduction in the duration of MV (MD −2.80 (−6.06, 0.47), p = 0.09; I² = 94%) but no differences in ICU-LOS (MD −0.26 (95%CI −0.89, 0.37), p = 0.42; I² = 75%) and mortality (RR = 0.85 (95%CI 0.63, 1.15), p = 0.30; I² = 0%). Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding.

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s disease).

The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).

The European Medicine Agency (EMA) has defined Adverse Drug Reactions (ADRs) as “a noxious and unintended response to a medicine”, not including poisoning, accidental, or intentional overdoses. The ADR occurrence differs based on the approach adopted for defining and detecting them, the characteristics of the population under study, and the research setting. ADRs have a significant impact on morbidity and mortality, particularly among older adults, and represent a financial burden for health services. Between 30% and 60% of ADRs might be predictable and preventable, emerging as a result of inappropriate prescription, drug chemistry inherent toxicity, cell-specific drug toxicity, age- and sex-related anomalies in drug absorption, distribution, metabolism, and elimination (ADME), and drug–drug interactions (DDIs) in combination therapies or when a patient is treated with different drugs for concomitant disorders. This is particularly important in chronic diseases which require long-term treatments. Rapid developments in pharmacogenetics/genomics have improved the understanding of ADRs accompanied by more accurate prescriptions and reduction in unnecessary costs. To alleviate the burden of ADRs, especially in the elderly, interventions focused on pharmaceutical principles, such as medication review and reconciliation, should be integrated into a broader assessment of patients’ characteristics, needs, and health priorities. Digital health interventions could offer valuable solutions to assist healthcare professionals in identifying inappropriate prescriptions and promoting patient adherence to pharmacotherapies.