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The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

The following article presents an analysis of the impact of the Environmental, Social and Governance-ESG determinants on Hospital Emigration to Another Region-HEAR in the Italian regions in the period 2004-2021. The data are analysed using Panel Data with Random Effects, Panel Data with Fixed Effects, Pooled Ordinary Least Squares-OLS, Weighted Least Squares-WLS, and Dynamic Panel at 1 Stage. Furthermore, to control endogeneity we also created instrumental variable models for each component of the ESG model. Results show that HEAR is negatively associated to the E, S and G component within the ESG model. The data were subjected to clustering with a k-Means algorithm optimized with the Silhouette coefficient. The optimal clustering with k=2 is compared to the sub-optimal cluster with k=3. The results suggest a negative relationship between the resident population and hospital emigration at regional level. Finally, a prediction is proposed with machine learning algorithms classified based on statistical performance. The results show that the Artificial Neural Network-ANN algorithm is the best predictor. The ANN predictions are critically analyzed in light of health economic policy directions.

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients’ health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03–0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005–0.08), and number of lost working days (Δ = − 7.9, 95% CI − 11.2 to − 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI − 1588–2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (− €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

Age-related hearing loss (ARHL), also called presbycusis, is a progressive disorder affecting hearing functions and among the elderly has been recognized as the third most frequent condition. Among ARHL components, the age-related central auditory processing disorder (CAPD) refers to changes in the auditory network, negatively impacting auditory perception and/or the speech communication performance. The relationship between auditory-perception and speech communication difficulties in age-related CAPD is difficult to establish, mainly because many older subjects have concomitant peripheral ARHL and age-related cognitive changes. In the last two decades, the association between cognitive impairment and ARHL has received great attention. Peripheral ARHL has recently been defined as the modifiable risk factor with the greatest impact on the development of dementia. Even if very few studies have analyzed the relationship between cognitive decline and age-related CAPD, a strong association was highlighted. Therefore, age-related CAPD could be a specific process related to neurodegeneration. Since these two disorders can be concomitant, drawing causal inferences is difficult. The assumption that ARHL, particularly age-related CAPD, may increase the risk of cognitive impairment in the elderly remains unchallenged. This review aims to summarize the evidence of associations between age-related CAPD and cognitive disorders and to define the diagnostic procedure of CAPD in the elderly. Finally, we highlight the importance of tailoring the rehabilitation strategy to this relationship. Future longitudinal studies with larger sample sizes and the use of adequate assessment tools that can disentangle cognitive dysfunction from sensory impairments are warranted.

Background Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. Methods In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). Results With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs . who survived 6.4 ± 3.3 days). T Conclusions The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.

Human apolipoprotein E (ApoE) is a 299-amino acid secreted glycoprotein that binds cholesterol and phospholipids. ApoE exists as three common isoforms (ApoE2, ApoE3, and ApoE4) and heterozygous carriers of the ε4 allele of the gene encoding ApoE (APOE) have a fourfold greater risk of developing Alzheimer’s disease (AD). The enzymes thrombin, cathepsin D, α-chymotrypsin-like serine protease, and high-temperature requirement serine protease A1 are responsible for ApoE proteolytic processing resulting in bioactive C-terminal-truncated fragments that vary depending on ApoE isoforms, brain region, aging, and neural injury. The objectives of the present narrative review were to describe ApoE processing, discussing current hypotheses about the potential role of various ApoE fragments in AD pathophysiology, and reviewing the current development status of different anti-ApoE drugs. The exact mechanism by which APOE gene variants increase/decrease AD risk and the role of ApoE fragments in the deposition are not fully understood, but APOE is known to directly affect tau-mediated neurodegeneration. ApoE fragments co-localize with neurofibrillary tangles and amyloid β (Aβ) plaques, and may cause neurodegeneration. Among anti-ApoE approaches, a fascinating strategy may be to therapeutically overexpress ApoE2 in APOE ε4/ε4 carriers through vector administration or liposomal delivery systems. Another approach involves reducing ApoE4 expression by intracerebroventricular antisense oligonucleotides that significantly decreased Aβ pathology in transgenic mice. Differences in the proteolytic processing of distinct ApoE isoforms and the use of ApoE fragments as mimetic peptides in AD treatment are also under investigation. Treatment with peptides that mimic the structural and biological properties of native ApoE may reduce Aβ deposition, tau hyperphosphorylation, and glial activation in mouse models of Aβ pathology. Alternative strategies involve the use of ApoE4 structure correctors, passive immunization to target a certain form of ApoE, conversion of the ApoE4 aminoacid sequence into that of ApoE3 or ApoE2, and inhibition of the ApoE-Aβ interaction.

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Background The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. Methods A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). Results Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting β 2 -agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. Conclusion A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1–3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1–77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.

People with severe/profound and multiple disabilities may receive insufficient stimulation and correspondingly show low levels of happiness (satisfaction). Various stimulation strategies have been proposed to address this situation. This study aimed to extend the assessment of two of those strategies (i.e., self-regulated and staff-regulated stimulation strategies) with 12 participants who were exposed to each strategy. During intervention sessions with self-regulated stimulation, the participants sat at a desk and received stimulation if they pushed a panel in front of them thus activating a smartphone’s proximity sensor. During intervention sessions with staff-regulated stimulation, they sat at a desk and received stimulation independent of any response. All participants showed increases in indices of satisfaction with self-regulated stimulation. Nine of them also showed such increases with staff-regulated stimulation. The participants’ level of satisfaction during self-regulated stimulation sessions was frequently higher than that observed during staff-regulated stimulation sessions. Staff personnel interviewed about the two strategies provided higher scores for self-regulated stimulation. The self-regulated stimulation strategy may be considered preferable to the staff-regulated stimulation strategy because of its impact on participants’ satisfaction and active responding.