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IntroductionCystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del is the most frequent mutation (70% of alleles in Italy), while other mutations have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% in Italy) emerges as a mutation characterized by a severe CFTR folding and trafficking defect.MethodsTo investigate the pharmacological responsiveness of the G85E-CFTR variant, we performed a functional and biochemical characterization in heterologous expression systems and ex vivo models based on patient-derived human nasal epithelial cells (HNEC).ResultsOur study demonstrated that treatment of primary airway cells with elexacaftor and tezacaftor causes a significant (although modest) rescue of CFTR function, that reaches 15%–25% of the activity measured in non-CF epithelia. A detrimental effect of chronic treatment with ivacaftor, further limiting G85E rescue, was also observed. A higher rescue of CFTR function, up to 25%–35% of the normal CFTR activity, with no evidence of negative effects upon chronic potentiator treatment, can be achieved by combining elexacaftor with ARN23765, a novel type 1 corrector endowed with very high potency. Importantly, dose-response relationships suggest that G85E might alter the binding of type 1 correctors, possibly affecting their affinity for the target.DiscussionIn conclusion, our studies suggest that novel combinations of modulators, endowed with higher efficacy leading to increased rescue of G85E-CFTR, are needed to improve the clinical benefit in patients for this variant.

Key Clinical Message Gallstones, microlithiasis, gallbladder sludge, and micro‐gallbladder are frequently reported in cystic fibrosis patients, and modulators could modify gallbladder disease, probably reducing biliary secretions viscosity.

Background: CardioMEMS is a device suitable for telemedicine that is currently being evaluated by the Regional Health Technology Assessment (HTA) Committee of Tuscany. Two detailed HTA reports are available in the specialized literature, the results of which need to be transferred to our regional setting. These decisions in Tuscany are made by the so-called Centro Operativo HTA. Aim: To validate, with local cost-effectiveness data, the decision on CardioMEMS that will be made in the Tuscany region. Methods: Two detailed international HTA reports were rearranged and adapted to our regional setting to generate a simplified analysis that could form the basis of our decision. Two willingness-to-pay (WTP) thresholds of €20,000/quality-adjusted life year (QALY) and €50,000/QALY were considered. Results: Based on epidemiological and regulatory information, the target population in Tuscany for this device is 166 cases. The value-based price of CardioMEMS is estimated to be €4,332 and €16,662 at WTP thresholds of 20,000/QALY and 50,000/QALY, respectively. Its current price in Italy is €12,000. Conclusion: In our region, the introduction of CardioMEMS is likely to be gradual, around 50 patients/year (or €0.60 million/year at current price). This example highlights the need to adapt the information published in the international literature to the local context in which the approval decision is made. In this context, simplified analyses are easier to apply than complex Markov models.

With the introduction of elexacaftor/tezacaftor/ivacaftor (ETI), more women with cystic fibrosis (CF) are likely to grow families. Hence, an understanding long-term safety and effects of CFTR modulators on fertile women and children while monitoring their concentrations is crucial. Here, we report on the development of an improved LC–MS/MS methodology to measure ETI concentrations in maternal and child blood and breastmilk, applied in one case of successful pregnancy of a 30-year-old woman with CF (F508del/R334W). We observed that ETI remains stable in breastmilk, is absorbed by the infant and can be detected in child plasma. Our results confirm accumulating evidence of a successful pregnancy in women treated with CFTR modulators without significant side effects on the child and provide valuable analytical procedures suitable for the post-marketing evaluation of CFTR modulators in pregnant and lactating women, as well as in their infants.

Objectives: Previous studies showed the clinical effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in cystic fibrosis (CF) patients and a recently published study evaluated twelve CF patients that performed chest and sinus computed tomography (CT) examinations and showed that ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment. The aim of the present study was to evaluate the role of CFTR modulator therapy in improving radiological and clinical scores one year after ETI therapy initiation in a wider CF patient population. Materials and methods: Between January 2020 and December 2022, 44 CF adult patients received elexacaftor-tezacaftor-ivacaftor (ETI) therapy for at least one year and underwent a chest CT examination at our hospital before and one year after ETI therapy initiation. Experienced radiologists who were blinded to the treatment assessed the images in consensus. The Brody-II score (BSII), the Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were evaluated. Clinical scores such as cystic fibrosis clinical score (CFCS), Cystic Fibrosis Questionnaire-Revised (CFQ-R) score, the 22-item SinoNasal Outcome Test (SNOT-22) questionnaire and the CF-specific 28-modal abdominal symptom score (CFAbd-Score) were evaluated. Forced expiratory volume in 1 ​s (FEV1) and forced vital capacity (FVC) were also assessed. Paired samples t-tests were used to compare differences before and after one year of ETI therapy initiation, and Pearson's correlation coefficient was used to evaluate changes in FEV1 and total BSII and in FVC and total BSII. Results: Total BIIS one year after ETI initiation showed statistically significant lower scores (−6.0 p, p ​

Background: Low coverage of influenza vaccination in nursing home (NH) staff may be attributed to factors such as vaccine confidence (VC) and vaccine literacy (VL). Our study aimed to evaluate the role of VL and VC in predicting the intention to get the influenza vaccine in a sample of employees of NHs in Tuscany, Italy. Methods: Data from staff members in Tuscany were collected using an online questionnaire that examined influenza vaccination history, intentions, demographic information, health status, and VL. Statistical analyses explored the relationships between VC, VL, and vaccination intentions. Results: The study included 1794 respondents, (86.3%) and assistants/aides (58.1%), with a median age of 46 years. The intention to get vaccinated was significantly higher among those with health risk conditions, and there was a positive association between VC and VL, specifically its interactive/critical component. The mediation analysis showed that VC completely mediated the relationship between VL and the intention to get vaccinated, with significant effects observed in different subgroups. Conclusions: VC is a key factor that mediates the effect of VL on vaccine intention. These results suggest that interventions aimed at improving VL alone may not be sufficient to increase vaccine uptake unless VC is also addressed.

BackgroundUtilization of Emergency Medical Services (EMS) declined during COVID-19 pandemic, but most of the studies analyzed components of the EMS system individually. The study aimed to evaluate the indirect impact of COVID-19 pandemic on the utilization of all the components of the EMS system of Tuscany Region (Italy) during the first pandemic wave.MethodsAdministrative data from the health care system of Tuscany were used. Changes in utilization for out-of-hospital emergency calls and emergency vehicle dispatched, emergency department (ED) visits, and patients being admitted from the ED to an inpatient hospital bed (hospitalizations from ED) during the first pandemic wave were analyzed in relation with corresponding periods of the previous two years. Percentage changes and 95%CI were calculated with Poisson models. Standardized Ratios were calculated to evaluate changes in in-hospital mortality and hospitalizations requiring ICU.ResultsSignificant declines were observed in the utilization of all the EMS considered starting from the week in which the first case of COVID-19 was diagnosed in Italy till the end of the first pandemic wave. During the epidemic peak, the maximum decreases were observed: -33% for the emergency calls, -45% for the dispatch of emergency vehicles, -71% for ED admissions. Furthermore, a decline of 37% for hospitalizations from ED was recorded. Significant decreases in ED admissions for life threatening medical conditions were observed: acute cerebrovascular disease (-36%, 95% CI: -43, -29), acute myocardial infarction (-42%, 95% CI: -52, -31) and renal failure (-42%, 95% CI: -52, -31). No significant differences were found between the observed and the expected in-hospital mortality and hospitalizations requiring ICU during the epidemic peak.ConclusionAll the components of the EMS showed large declines in their utilization during COVID-19 pandemic; furthermore, major reductions were observed for admissions for time-dependent and life-threatening conditions. Efforts should be made to ensure access to safe and high-quality emergency care during pandemic.

Six Minute Walk Test (6MWT) is a field exercise test widely used in clinical practice, both in adults and in pediatric patients. The primary aim of the study is to evaluate the physical performance of the subjects and compare them with the predicted Italian values. The secondary aim is to verify the possible relationship between the 6MWT distance (6MWD) and the clinical variables of the sample. Italian children between 6-11 years affected by CF were recruited from 9 regional centres for CF. Short questionnaire assessments about their health state and physical activity routine was administered. Anthropometric characteristics were measured before the test and, peripheral oxygen saturation (SpO2), heart and respiratory rate were measured before and after a 6-minute walk test. The tests were performed according to the American Thoracic Society (ATS) guidelines. 6MWD was compared with the predicted distance calculated by the reference equation for healthy subjects of the same age.A total of 132 children were recruited (70 male) and completed the assessment. The mean (±SD) for 6MWD was 557.4(±69.9), male = 551.4(±80.0), female = 560.4(±63.3), however the predicted distance mean was 605m. A total of 101(76.5%) subjects practice regular physical activity. A total of 31(23%) had a FEV1 lower than their Lower Limits of Normal (LLN). Functional performance on the 6MWT was poorer among the CF patients than among the predicted distance estimated with Italian values. The correlation with the amount of physical activity and 6MWD has been verified.

Vaccine literacy (VL) mediates the transfer of information and facilitates vaccination acceptance. The aims of this study are to validate the HLVa-IT (Health Literacy Vaccinale degli adulti in Italiano—Vaccine health literacy for adults in Italian language) for the staff of nursing homes (NHs), to measure VL in such a peculiar target group, and to assess its relationship with the sources used to obtain information about vaccines and vaccinations. A survey has been conducted in a sample of Tuscan NHs using an online questionnaire. Eight-hundred and fifty-three questionnaires were analyzed. Two dimensions of the HLVa-IT appeared (functional and interactive/communicative/critical VL). The HLVa-IT interactive/communicative/critical subscale score was slightly higher than the functional subscale, although with no statistical significance. General practitioners (GPs) or other professionals have been reported as the main source of information by most of the respondents (66.1%). The HLVa-IT total score was significantly higher among those who have declared to use official vaccination campaigns (mean score: 3.25 ± 0.49; p < 0.001), GPs or other health professionals (3.26 ± 0.47; p < 0.001), and search engines (3.27 ± 0.48; p = 0.040) as the main sources of information. In conclusion, the HLVa-IT could be reliable test to investigate VL for staff of NHs, and also to highlight criticalities related to information sources.

Purpose Heart failure (HF) is recognized as a major problem in industrialized countries. Short-term adjusted outcomes are indicators of quality for care process during/after hospitalization. Our aim is to evaluate, for patients with principal diagnosis of HF, in-hospital mortality and 30-day readmissions for all-causes using two different risk adjustment (RA) tools. Methods and Results We used data from the hospital discharge abstract (HD) of a retrospective cohort of patients (2002-2007) admitted in Tuscan hospitals, Italy. Considered outcomes were in-hospital mortality and readmission at 30 days. We compared the All-Patients Refined Diagnosis Related Groups (APR-DRG) system and the Elixhauser Index (EI). Logistic regression was performed and models were compared using the C statistic (C). examined records were 58.202. Crude in-hospital mortality was 9.7%. Thirty-day readmission was 5.1%. The APR-DRG class of risk of death (ROD) was a predictive factor for in-hospital mortality; the APR-DRG class of severity was not significantly associated with 30-day readmissions (P>0.05). EI comorbidities which were more strongly associated with outcomes were nonmetastatic cancer for in-hospital mortality (odds ratio, OR 2.25, P

(1) Background: Influenza vaccination uptake in nursing home (NH) workers is uncommon. The aim of this study was to understand the choice architecture of influenza vaccination acceptance or refusal among them and to promote vaccination acceptance using the nudge approach. (2) Methods: In autumn 2019, a nudge intervention with a contextual qualitative analysis of choice architecture of vaccination was performed among the staff of eight Tuscan NHs. In summer 2020, a cross-sectional study including the staff of 111 NHs (8 in the nudge, 103 in the comparison group) was conducted to assess the impact of the nudge intervention in promoting vaccination uptake. (3) Results: Macro-categories of motivations for vaccination uptake that emerged from the qualitative analysis were risk perception, value dimension, and trust, while those regarding refusal were risk perception, distrust, value dimension, and reasons related to one’s health. Considering the cross-sectional study, influenza vaccination uptake in the 2018–2019 season was similar in the two groups (23.6% vs. 22.2% respectively, in the nudge and comparison group), but significantly different in the 2019–2020 season: 28% in the nudge vs. 20% in the comparison group. Also, the intention to get the vaccine in the 2020–2021 season was significantly different in the two groups: 37.9% in the nudge and 30.8% in the comparison group. (4) Conclusions: Nudge interventions-simple, fast, low cost-could be effective in promoting vaccination acceptance among NH workers and the analysis of choice architecture could be useful in improving tailored, new nudge interventions aimed at modifying irrational biased and cognitive errors.

The aim of this cross-sectional study is to address whether health literacy (HL) and vaccine confidence are related with influenza vaccination uptake among staff of nursing homes (NHs). It was conducted in Tuscany (Italy) in autumn 2018, including the staff of 28 NHs. A questionnaire was used to collect individual data regarding influenza vaccination in 2016–2017 and 2017–2018 seasons; the intention to be vaccinated in 2018–2019; as well as demographic, educational, and health information. It included also the Italian Medical Term Recognition (IMETER) test to measure HL and eight Likert-type statements to calculate a Vaccine Confidence Index (VCI). The number of employees that fulfilled the questionnaire was 710. The percentage of influenza vaccination uptake was low: only 9.6% got vaccinated in 2016–2017 and 2017–2018 and intended to vaccinate in 2018–2019. The VCI score and the IMETER-adjusted scores were weakly correlated (Rho = 0.156). At the multinomial logistic regression analysis, the VCI was a positive predictor of vaccination uptake. In conclusion, vaccine confidence is the strongest predictor of influenza vaccination uptake among the staff of NHs. The development of an adequate vaccine literacy measurement tool could be useful to understand whether skills could be related to vaccine confidence.

BACKGROUND:Cancer, chronic heart failure (CHF), and chronic obstructive pulmonary disease (COPD) in the advanced stages have similar symptom burdens and survival rates. Despite these similarities, the majority of the attention directed to improving the quality of end-of-life (EOL) care has focused on cancer. AIM:To assess the extent to which the quality of EOL care received by cancer, CHF, and COPD patients in the last month of life is diagnosis-sensitive. METHODS:This is a retrospective observational study based on administrative data. The study population includes all Tuscany region residents aged 18 years or older who died with a clinical history of cancer, CHF, or COPD. Decedents were categorized into two mutually exclusive diagnosis categories: cancer (CA) and cardiopulmonary failure (CPF). Several EOL care quality outcome measures were adopted. Multivariable generalized linear model for each outcome were performed. RESULTS:The sample included 30,217 decedents. CPF patients were about 1.5 times more likely than cancer patients to die in an acute care hospital (RR 1.59, 95% C.I.: 1.54-1.63). CPF patients were more likely to be hospitalized or admitted to the emergency department (RR 1.09, 95% C.I.: 1.07-1.10; RR 1.15, 95% C.I.: 1.13-1.18, respectively) and less likely to use hospice services (RR 0.08, 95% C.I.: 0.07-0.09) than cancer patients in the last month of life. CPF patients had a four- and two-fold higher risk of intensive care unit admission or of undergoing life-sustaining treatments, respectively, than cancer patients (RR 3.71, 95% C.I.: 3.40-4.04; RR 2.43, 95% C.I.: 2.27-2.60, respectively). CONCLUSION:The study has highlighted the presence of significant differences in the quality of EOL care received in the last month of life by COPD and CHF compared with cancer patients. Further studies are needed to better elucidate the extent and the avoidability of these diagnosis-related differences in the quality of EOL care.

Background: The Italian National Health System was revised in the last 20 years, introducing new elements such as efficacy, efficiency and competitiveness. Devolution to regional authorities has created a quasi-market system where patients can choose the hospital in which to be treated. Patient mobility therefore becomes an indicator of perceived hospital quality and of financial flows between the regions of Italy. Previous studies analyzed patient mobility in general or by specific disease/diagnosis-related groups but there is a lack of research on the influence of severity of patient condition. The aim of the study was to describe patient mobility, crude and stratified by disease severity, in cardiac surgery units of three health areas (HAs) in Tuscany (Italy). Methods: In this retrospective observational study, data was gathered from hospital discharge records obtained from the Tuscan Regional Health Agency, Italy. The three HAs (HA1, HA2, HA3) recorded 25,017 planned hospitalizations in cardiac surgery units in the period 2001-2007. Patients were stratified in four All Patient Refined Diagnosis Related Group (APR-DRG) severity levels. Gandy's nomogram was used to describe how HAs met health care demand and their capacity to attract patients. Cuzick's test was used to identify significant differences in time trends. Results: Raw data showed that the HAs met their own local health care demand. Stratifying by APR-DRG severity, it emerged that capacity to meet local demand remained unchanged for zero-to-minor severity levels, but one HA was less able to meet demand for moderate severity levels or to attract patients from other HAs and Regions of Italy. In fact, HA3 showed a decrease in admissions of local residents. Conclusions: The study highlights important differences between the three HAs that were only revealed by severity stratification: unlike HA3, HA1 and HA2 seemed able to deal with local demand, even after severity stratification. Planners and researchers can benefit from risk stratification data, which provides more elements for correct comparisons and interventions. In the context of patient mobility, the present study is a step in that direction. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to measure the prevalence of pressure ulcers (PrUs) in an older adult population., Design: A cross-sectional study., Setting: The study included all the individuals being cared for in the units of medicine, surgery, intensive care, and medical-surgical specialties of 47 hospitals, 57 public nursing homes, and 37 home care services., Participants: The authors' observational study included 11,957 patients older than 70 years., Main Outcome Measures: Of the population, 50.75% (6067) were assessed to be at risk of developing PrUs according to the Braden Scale, and 24.66% (2949) had already developed PrUs. In addition, a significant association was found between increased risk (Braden <16) and the presence of PrUs with an odds ratio (OR) of 8.71 (confidence interval [CI], 7.52-10.10) in high-risk subjects (Braden ≤ 12) and an OR of 3.86 (CI, 3.36-4.44) in very high-risk patients (Braden 13-16). In the survey, 84.6% of the subjects with PrUs were incontinent, and incontinence increased the risk of developing PrUs in the authors' sample (OR, 1.54; CI, 1.34-1.77)., Conclusions: The authors' data reported in the literature show that the prevalence of PrUs increases as an individual ages. The authors gathered data that showed a large area of intervention in managing the prevention of PrUs, such as an adequate use of protective aids, correcting malnutrition, and controlling incontinence. These results suggest that clinicians should focus more on the prevention of PrUs in older adults.