Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

A realistic approach for evaluating antimicrobial surfaces for dry surface exposure scenarios.

The severe acute respiratory syndrome coronavirus 2 pandemic has raised public awareness about the importance of hygiene, leading to an increased demand for antimicrobial surfaces to minimize microbial contamination on high-touch surfaces. This is particularly relevant in public and private transportation settings, where surfaces frequently touched by individuals pose a significant, yet preventable, risk of infection transmission. Typically, the antimicrobial activity of surfaces is tested using test methods of the International Standards Organization, American Society for Testing and Materials, or Japanese Industrial Standards, which involve complete submersion in liquid, elevated temperature (37°C), and prolonged (24 h) contact periods. However, these conditions do not accurately represent real-world scenarios where surfaces are exposed to air. In this study, we propose a modified test method designed to better reflect real-life conditions in the intended end-use setting. The modifications included using deionized water instead of nutrient broth while preparing bacterial inoculum, applying a small test inoculum to the surface and allowing it to dry, maintaining ambient temperature and relative humidity throughout the contact period, and reducing the contact period to 4 h. With this modified approach, the antimicrobial activity of 20 samples was reassessed. This screening revealed that out of 20 samples, only 2 samples were effective against all species, while 8 samples demonstrated partial effectiveness against selected species, and 10 samples showed no significant effect. These findings highlight the inadequacy of the current test standard and emphasize the urgent necessity for revised and adapted testing method to ensure a reliable and accurate evaluation.IMPORTANCEThe recent severe acute respiratory syndrome coronavirus 2 pandemic has sparked increased demand for antimicrobial surfaces to mitigate the risk of fomites-transmitted infection in both indoors and confined spaces. Commonly, the antimicrobial activity of these surfaces is assessed using test standards established by national standards bodies, which do not distinguish between different application scenarios. While these test standards are suitable for surfaces intended for submerged application, they are inappropriate for antimicrobial surfaces designed for dry surface exposure. The usage of these standards can lead to an overestimation of antimicrobial efficacy. Thus, this study introduces a modified dry exposure test method aimed at better reflecting real-life conditions in the intended end-use setting. Our results revealed the subpar antimicrobial performance of numerous samples, highlighting the necessity to revise and tailor the universal test standard to real-world scenarios in order to ensure a reliable and accurate evaluation.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

OBJECTIVES: to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. METHODS: SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. RESULTS: One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]. CONCLUSION: rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes.

BACKGROUND: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). METHODS: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. RESULTS: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. CONCLUSION: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

A real-life study of daratumumab-bortezomib-dexamethasone (D-VD) in lenalidomide exposed/refractory multiple myeloma patients: a report from the Triveneto Myeloma Working Group.

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3-4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting.

Impact of minimal residual disease response and of status of disease on survival after blinatumomab in B-cell acute lymphoblastic leukemia: results from a real-life study.

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.

Real-life use of ropeg-interferon α2b in polycythemia vera: patient selection and clinical outcomes.

Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

Economic evaluation of anti-CD19 CAR T-cell pathway for large B-cell lymphomas in the real-life setting: the experience of an Italian hub center in the first three years of activity.

Poor literature report actual and detailed costs of chimeric antigen receptor (CAR) T-cell pathway in a real-life setting. We retrospectively collect data for all patients with relapsed/refractory aggressive large B-cell lymphoma who underwent leukapheresis between August 2019 and August 2022. All costs and medical resource consumption accountability were calculated on an intention-to-treat (ITT) basis, starting from leukapheresis to the time when the patient (infused or not) exited the CAR T-cell pathway for any reason. Eighty patients were addressed to leukapheresis and 59 were finally infused. After excluding CAR-T product cost, the main driver of higher costs were hospitalizations followed by the examinations/procedures and other drugs, respectively 43.9%, 26.3% and 25.4% of the total. Regarding costs of drugs and medications other than CAR T products, the most expensive items are those referred to AEs, both infective and extra-infective within 30 days from infusion, that account for 63% of the total. Density plot of cost analyses did not show any statistically significant difference with respect to the years of leukapheresis or infusion. To achieve finally 59/80 infused patients the per capita patients without CAR-T products results 74,000 euros. This analysis covers a growing concern on health systems, the burden of expenses related to CAR T-cell therapy, which appears to provide significant clinical benefit despite its high cost, thus making economic evaluations highly relevant. The relevance of this study should be also viewed in light of continuously evolving indications for this therapy.

Treatment trends for undescended testis and impact of guideline changes a medical health care analysis of orchidopexy and cryptorchidism in Germany between 2006 und 2020.

BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Real-life hypoglycaemia partially blunts the inflammatory response to experimental hypoglycaemia in people with type 1 diabetes.

AIM: To determine whether recent repeated exposure to real-life hypoglycaemia affects the pro-inflammatory response during a hypoglycemia episode. MATERIALS AND METHODS: This was a post hoc analysis of a hyperinsulinaemic normoglycaemic-hypoglycaemic clamp study, involving 40 participants with type 1 diabetes. Glucose levels 1 week before the clamp were monitored using a Freestyle Libre 1. Blood was drawn during normoglycaemia and hypoglycaemia, and 24 hours after resolution of hypoglycaemia for measurements of inflammatory responses and counterregulatory hormone levels. We determined the relationship between the frequency and duration of spontaneous hypoglycaemia, and time below range (TBR) and the inflammatory response to experimental hypoglycaemia. RESULTS: On average, participants experienced 0.79 (0.43, 1.14) hypoglycaemia episodes per day, with a duration of 78 (47, 110) minutes and TBR of 5.5% (2.8%, 8.5%). TBR and hypoglycaemia frequency were inversely associated with the increase in circulating granulocyte and lymphocyte counts during experimental hypoglycaemia (P < .05 for all). A protein network consisting of DNER, IF-R, uPA, Flt3L, FGF-5 and TWEAK was negatively associated with hypoglycaemia frequency (P < .05), but not with the adrenaline response. Neither other counterregulatory hormones, nor hypoglycaemia awareness status, was associated with any of the inflammatory parameters markers. CONCLUSIONS: Repeated exposure to spontaneous hypoglycaemia is associated with blunted effects of subsequent experimental hypoglycaemia on circulating immune cells and the number of inflammatory proteins.

Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort: Real-Life Experience From Spain.

BACKGROUND: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. OBJECTIVE: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. METHODS: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. RESULTS: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/µL, or viral load >100 000 copies/mL were associated with therapeutic failure. CONCLUSION AND RELEVANCE: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.

Dabrafenib-trametinib in BRAF V600-mutated non-small-cell lung cancer: a single center real world experience.

Aim: We retrospectively evaluated the effect of dabrafenib/trametinib combination in patients with BRAF-mutated non-small-cell lung cancer (NSCLC) treated in a single center from 2017 to 2022.Patients: The response and safety data of 42 patients (27 treated in first-line and 15 as second/subsequent lines) were analyzed.Results: The objective response was 73.8%, with no differences between patients undergoing first- or second-line. A longer, statistically significant median progression-free survival (PFS) was observed in patients receiving the combination in first-line vs those in the second/subsequent lines (19.9 months [95% CI: 19.7-20] vs 13.1 months [95% CI: 8.6-17.6], respectively; p = 0.012). The median overall survival (OS) was 29.9 months (95% CI: 14.1-45.7) for patients treated with the combination in first-line and 22.4 months (95% CI: 14.6-30.2) for those treated in subsequent lines. The combination was well toleratedConclusion: We confirm the efficacy of dabrafenib/trametinib in BRAF-V600-mutated NSCLC.

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A European, Observational, 3-Year Cohort Comparative Study on the Safety of the Fixed Dose Combination Pravastatin 40 mg/Fenofibrate 160 mg vs. Statin Alone in Real Clinical Practice: The POSE Study.

BACKGROUND AND PURPOSE: The aim of the study was to provide valuable real-world long-term safety data of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in comparison of monotherapy with statins of moderate intensity. MATERIALS AND METHODS: POSE study was an observational, comparative study conducted in three European countries. Patients treated or planned to be treated with pravastatin 40 mg/fenofibrate 160 mg or with a moderate-intensity statin in monotherapy were assessed over 3 years. The main safety endpoints included the incidence of renal or urinary disorder, musculoskeletal or connective tissue disorder, hepatobiliary disorder and cardiovascular events. RESULTS: The study included 3075 patients treated for dyslipidaemia, with diabetes mellitus (47%), hypertension (56%) and/or established cardiovascular disease (61%). Over the 3 years of follow-up, the difference in incidence rate of safety events between the pravastatin 40 mg/fenofibrate 160 mg group and the statin group was not statistically significant (RR = 1.366 [95% CI = 0.967-1.929]). The most frequently occurring events were musculoskeletal and connective tissue disorders (AR = 0.030 in the pravastatin 40 mg/fenofibrate 160 mg group and 0.024 in the statin group), renal and urinary disorders (AR = 0.019 vs. 0.016, respectively) and aggravated diabetes mellitus (0.021 vs. 0.014). Most events occurred during the first year, then incidence decreased over the 3-year period. No statistically significant difference was observed between treatment groups regarding the cardiovascular events (RR = 1.209 [95% CI = 0.596-2.453]) and no new signal emerged from the long-term follow-up. CONCLUSIONS: This study demonstrates a reassuring long-term safety profile of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in routine clinical practice, with low and similar incidence of events over the 3 years follow-up compared to a monotherapy with statins of moderate intensity.

Real-world use of Safinamide in motor fluctuating Parkinson's disease patients in Italy.

INTRODUCTION: Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. METHODS: We performed a sub-analysis of the Italian cohort of the SYNAPSES study, a multi-country, multi-center, retrospective-prospective cohort observational study, designed to investigate the use of safinamide in routine clinical practice. Patients received for the first time a treatment with safinamide and were followed up for 12 months. The analysis was conducted on the overall population and in subgroups of interest: i) patients > 75 years, ii) patients with relevant comorbidities and iii) patients affected by psychiatric symptoms. RESULTS: Italy enrolled 616/1610 patients in 52 centers, accounting for 38% of the entire SYNAPSES cohort. Of the patients enrolled, 86.0% were evaluable at 12 months, with 23.3% being > 75 years, 42.4% with psychiatric conditions and 67.7% with relevant comorbidities. Safinamide was effective on motor symptoms and fluctuations as measured through the Unified PD rating scale III and IV scores, and on the total score, without safety issues in none of the subgroups considered. CONCLUSION: The SYNAPSES data related to Italian patients confirms the good safety profile of safinamide even in special groups of patients. Motor fluctuations and motor impairment improved at the follow-up suggesting the significant role of safinamide in managing motor symptoms in PD patients.

Real-life management of patients with mild cognitive impairment: an Italian survey.

BACKGROUND: Mild cognitive impairment (MCI) is a syndrome with heterogeneous underlying causes and different rates of disease progression, whose clinical heterogeneity leads to a wide variation in diagnostic and therapeutic approaches in clinical practice. The lack of uniform practical recommendations on diagnostic workup and treatment for MCI patients hinders optimal management of these patients, worsening their prognosis. Standardized guidelines for the investigation and follow-up of MCI are therefore urgently required. AIM: Aim of our study was to assess the diagnostic and therapeutic approach to MCI patients in the setting of Italian Memory Clinics. METHODS: A survey was delivered to a sample of Italian neurologists through two different phases: a first exploratory phase recording general information about the usual clinical management of patients with MCI, and a subsequent operative phase assessing the practical diagnostic and therapeutic decisions taken in a real life setting to manage subjects with MCI. RESULTS: A total of 121 neurologists participated to the first phase of the survey and 203 patients were enrolled in the second phase. Information gathered in the first phase of the survey highlighted a non-uniform use of diagnostic criteria and procedures for MCI, as well as a very heterogeneous therapeutic strategy among Italian neurologists. In the second phase, recorded data on diagnostic and therapeutic approach confirmed the large variability observed in the first phase of the survey. CONCLUSIONS: The results of our study reflect a suboptimal management of MCI patients in Italy and highlight the need of standardized diagnostic and therapeutic approaches for this condition.

What Is the Real-Life Experience of Older Adults on Smart Healthcare Technologies? An Exploratory Interview Study.

INTRODUCTION: Smart healthcare technologies (SHCTs) exhibit the great potential to support older Hong Kong adults with their health problems. Although there are various SHCTs in the Hong Kong market, and some adoption predictors have been proposed and investigated, little is known about older users' views on and real-life experiences with these technologies. This exploratory study examined the experiences, functional needs, and barriers of three kinds of SHCT (i.e., smart wearable devices, smart health monitors, and healthcare applications) with older adults in real life. METHODS: A convenience sampling method was applied to recruit twenty-two older adults from the Hong Kong community. The interview was designed in semi-structured and conducted in a face-to-face setting. The content analysis was used to summarize the older adults' functional needs and barriers in real life. RESULTS: We found older adults mainly applied SHCTs to address physical health, but there are few technological solutions for mental health in practice. There are four types of barriers in using SHCT. However, social support in Hong Kong community greatly helps reduce the barriers in technology use. Based on the findings, we discussed the possible solutions based on the social and technology perspective. CONCLUSION: Current technologies still could not fully address older adults' needs for healthy aging, and various barriers still hinder the actual adoption. By deeply understanding and considering the social context, technology innovation can facilitate the adoption of SHCT and promote a healthy aging society.

Personalized sleep and nutritional strategies to combat adverse effects of night shift work: a controlled intervention protocol.

BACKGROUND: Working during the night interferes with the timing of normal daily activities and is associated with an increased risk of chronic diseases. Under controlled experimental conditions, interventions focusing on sleep and nutrition can mitigate the short-term adverse effects of shift work. However, it is unclear how these results translate to real-life, how they can be targeted to individual conditions, and how they relate to long-term health. Therefore, the current study aims to implement a personalized sleep and nutritional intervention among night shift workers in the field. METHODS: A non-blinded controlled intervention study is used, consisting of a run-in period, an intervention of 3 months, post-intervention measurements, and a follow-up after 12 months. Three study arms are included: sleep intervention, nutritional intervention, and control group (n = 25 each). Participants are healthy 18-60-year male night shift workers, with at least one year of experience in night shift work. Information from the run-in period will be used to personalize the interventions. The main outcomes are sleep measurements and continuous interstitial glucose levels. Furthermore, general health biomarkers and parameters will be determined to further evaluate effects on long-term health. DISCUSSION: This study aims to mitigate negative health consequences associated with night shift work by introducing two personalized preventive interventions. If proven effective, the personalized interventions may serve as practical solutions that can have a meaningful impact on the sustainable health and employability of night shift workers. This study will thereby contribute to the current need for high-quality data on preventative strategies for night shift work in a real-life context. TRIAL REGISTRATION: This trial has been registered under ClinicalTrials.gov Identifier NCT06147089. Registered 27 November 2023.

Real-life experience after 3 months with tezepelumab before marketing approval.

BACKGROUND: Tezepelumab is a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), implicated in asthma pathogenesis, and that has been approved for patients with severe uncontrolled asthma in Spain in October 2023. This study evaluates our experience with Tezepelumab for those patients who received the indicated drug off-label prior to its commercialization. METHODS: We conducted a real-life observational study on three patients from the Severe Asthma Unit of the Hospital Universitario de Fuenlabrada, Spain, who received Tezepelumab off-label before its official approval. We analyzed symptoms control based on ACT, exacerbations, reductions in the doses of oral corticosteroid, lung function, blood changes and safety at 3 months of treatment. RESULTS: Tezepelumab demonstrated efficacy in improving asthma control and a notable reduction in emergency department visits. OCS use decreased, with one patient halving their prednisone dose. Lung function, particularly FEV1 and FEV1/FVC parameters, improved, but no significant changes were observed in FeNO levels, blood eosinophil counts and total IgE. The treatment exhibited a favorable safety profile with no reported adverse effects during the study period. CONCLUSIONS: In this preliminary real-world experience prior to the official approval of tezepelumab in Spain, this monoclonal antibody showed promising results and suggests its potential as a valuable alternative for the treatment of severe asthma.