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Many factors have contributed to rendering frailty an emerging, relevant, and very popular concept. First, many pandemics that have affected humanity in history, including COVID-19, most recently, have had more severe effects on frail people compared to non-frail ones. Second, the increase in human life expectancy observed in many developed countries, including Italy has led to a rise in the percentage of the older population that is more likely to be frail, which is why frailty is much a more common concern among geriatricians compared to other the various health-care professionals. Third, the stratification of people according to the occurrence and the degree of frailty allows healthcare decision makers to adequately plan for the allocation of available human professional and economic resources. Since frailty is considered to be fully preventable, there are relevant consequences in terms of potential benefits both in terms of the clinical outcome and healthcare costs. Frailty is becoming a popular, pervasive, and almost omnipresent concept in many different contexts, including clinical medicine, physical health, lifestyle behavior, mental health, health policy, and socio-economic planning sciences. The emergence of the new "science of frailty" has been recently acknowledged. However, there is still debate on the exact definition of frailty, the pathogenic mechanisms involved, the most appropriate method to assess frailty, and consequently, who should be considered frail. This narrative review aims to analyze frailty from many different aspects and points of view, with a special focus on the proposed pathogenic mechanisms, the various factors that have been considered in the assessment of frailty, and the emerging role of biomarkers in the early recognition of frailty, particularly on the role of mitochondria. According to the extensive literature on this topic, it is clear that frailty is a very complex syndrome, involving many different domains and affecting multiple physiological systems. Therefore, its management should be directed towards a comprehensive and multifaceted holistic approach and a personalized intervention strategy to slow down its progression or even to completely reverse the course of this condition. [ABSTRACT FROM AUTHOR]

Background Little clinical research on new-generation heat-not-burn cigarettes ( HNBC ) in comparison with electronic vaping cigarettes ( EVC ) and traditional tobacco combustion cigarettes ( TC ) has been reported. We aimed to appraise the acute effects of single use of HNBC , EVC, and TC in healthy smokers. Methods and Results This was an independent, cross-over, randomized trial in 20 TC smokers, with allocation to different cycles of HNBC , EVC , and TC . All participants used all types of products, with an intercycle washout of 1 week. End points were oxidative stress, antioxidant reserve, platelet activation, flow-mediated dilation, blood pressure, and satisfaction scores. Single use of any product led to an adverse impact on oxidative stress, antioxidant reserve, platelet function, flow-mediated dilation, and blood pressure. HNBC had less impact than EVC and TC on soluble Nox2-derived peptide (respectively, P=0.004 and 0.001), 8-iso-prostaglandin F2α- III ( P=0.004 and <0.001), and vitamin E ( P=0.018 and 0.044). HNBC and EVC were equally less impactful than TCs on flow-mediated dilation ( P=0.872 for HNBC versus EVC ), H 2 O 2 ( P=0.522), H 2 O 2 breakdown activity ( P=0.091), soluble CD 40 ligand ( P=0.849), and soluble P-selectin ( P=0.821). The effect of HNBC and, to a lesser extent EVC , on blood pressure was less evident than that of TC , whereas HNBC appeared more satisfying than EVC (all P<0.05). Conclusions Acute effects of HNBC , EVC, and TC are different on several oxidative stress, antioxidant reserve, platelet function, cardiovascular, and satisfaction dimensions, with TCs showing the most detrimental changes in clinically relevant features. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03301129.

Background: The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique., Methods: Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway., Results: Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (€ 8.23), whilst the most expensive is continuous peripheral nerve block (€ 223.46). The intravenous patient-controlled analgesia costs € 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (€ 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (€0.58€) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re nata is associated to the lowest cost in terms of health professionals involved (€ 6.25), whilst intravenous PCA is the most expensive one (€ 245.66), requiring a massive monitoring on the part of physicians and nurses., Conclusions: The analysis successfully collected information about costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in all the nine different Italian hospitals. The interview showed high heterogeneity in the treatment of moderate to severe pain after major abdominal, orthopedic and thoracic surgeries among responding anesthesiologists, with 15 different analgesic modalities reported. The majority of the analgesic techniques considered in the analysis is not recommended by any guideline and their application in real life can be one of the reasons for the high incidence of uncontrolled pain, which is still reported in the postoperative period. Health care costs have become more and more important, although the choice of the best analgesic treatment should be a compromise between efficacy and economic considerations.