Trend of Bronchial Hyperresponsiveness to Methacholine as a Cost Predictor of Mild-to-Moderate Asthma: A Twelve-Month Survey in Teenagers.

Bronchial asthma is characterized by variable airflow obstruction, airway inflammation, and bronchial hyperresponsiveness (BHR) to non-specific stimuli. The role of underlying airway inflammation and of related long-lasting BHR has been suboptimally investigated in teenagers with mild-to-moderate asthma, as has the corresponding economic impact over time. The aim of the present study was to calculate the cost of mild-to-moderate atopic asthma in teenagers arising from their degree of persisting BHR over a twelve-month period. METHODS: Patients aged 12-18 years with mild-to-moderate symptoms treated with fluticasone fumarate/vilanterol 92/22 mcg daily were retrospectively followed for 12 months. Usual spirometric parameters, BHR to methacholine (MCh), and resource consumption (visits, hospitalizations, systemic steroids and/or antibiotics courses, school days off) were assessed at recruitment (the index date) and after 6 and 12 months. Adherence to treatment was also calculated. The cost of asthma was calculated based on Italian tariffs and published papers. The trend over time in BHR and the association between response to MCh and total cost were investigated by using regression models adjusted for repeated measures. RESULTS: 106 teenagers (53 males, age 15.9 ± 1.6 years) were investigated. The annual cost of asthma proved significantly related to the BHR trend: every increment of a factor 10 in the response to MCh was associated with a saving of EUR 184.90 (95% CI -305.89 to -63.90). BHR was progressively optimized after 6 and 12 months in relation to the patients' compliance to treatment (≥70% of prescribed inhalation doses). CONCLUSIONS: the usual spirometric parameters are largely insufficient to reflect the effects of underlying persistent inflammation in milder forms of asthma in teenagers. In terms of clinical governance, the periodic assessment of non-specific BHR is the appropriate procedure from this point of view. Non-specific BHR proves a reliable procedure for predicting and monitoring the economic impact of mild-to-moderate asthma in teenagers over time.

Cost-utility analysis of real-time artificial intelligence-assisted colonoscopy in Italy.

Background and study aims Artificial intelligence (AI)-assisted colonoscopy has proven to be effective compared with colonoscopy alone in an average-risk population. We aimed to evaluate the cost-utility of GI GENIUS, the first marketed real-time AI system in an Italian high-risk population. Methods A 1-year cycle cohort Markov model was developed to simulate the disease evolution of a cohort of Italian individuals positive on fecal immunochemical test (FIT), aged 50 years, undergoing colonoscopy with or without the AI system. Adenoma or colorectal cancer (CRC) were identified according to detection rates specific for each technique. Costs were estimated from the Italian National Health Service perspective. Results Colonoscopy+AI system was dominant with respect to standard colonoscopy. The GI GENIUS system prevented 155 CRC cases (-2.7%), 77 CRC-related deaths (-2.8%), and improved quality of life (+0.027 QALY) with respect to colonoscopy alone. The increase in screening cost (+€10.50) and care for adenoma (+€3.53) was offset by the savings in cost of care for CRC (-€28.37), leading to a total savings of €14.34 per patient. Probabilistic sensitivity analysis confirmed the cost-efficacy of the AI system (almost 80% probability). Conclusions The implementation of AI detection tools in colonoscopy after patients test FIT-positive seems to be a cost-saving strategy for preventing CRC incidence and mortality.

Benefits of MR-proADM-guided decision-making in the emergency department: clinical and economic evaluation in Italy, Germany, Spain, and the UK.

AIM: In a randomized control trial mid-regional proadrenomedullin (MR-proADM)-guided decision-making has been proven to safely reduce hospital admissions based on an accurate assessment of disease severity in the Emergency Department (ED). This study aimed to assess the impact of a MR-proADM-Guided Triage (MR-GT) versus standard Hospital Triage (HT) on clinical and economic outcomes in ED patients with suspected infection in Spain, Italy, Germany, and the UK, using Patient-Level Data (PLD) from two observational studies. METHODS: PLD was collected from patients enrolled at a Spanish hospital during two observational studies. Logistic regression was used to identify predictors of hospitalization. A patient-level simulation model was subsequently developed to evaluate the clinical and economic impact of MR-GT versus HT using results from the statistical analysis and country-specific cost data from the published literature. Probabilistic and deterministic sensitivity analyses were carried out. RESULTS: Four hundred seventy-three patients were enrolled in this study. MR-proADM had the strongest association with hospital admission, followed by age and National Early Warning Score (NEWS). In the simulation model, MR-GT was associated with an overall reduction in hospitalization relative to HT, equal to 22.6 percentage points (40.9 vs. 63.5%). In addition, the use of MR-GT would reduce the total hospital cost per patient presenting to the ED with suspected infection by roughly 30%, with a mean cost saving per patient of €626, €1,484, €1,154, and £1,113 in Spain, Italy, Germany, and the UK, respectively. The robustness of these findings was confirmed by sensitivity analyses. LIMITATIONS: The statistical analyses were not performed on the same population simulated in the model. Clinical input parameters were assumed to be the same for all countries. CONCLUSIONS: MR-proADM showed to be the main predictor of hospitalization. An MR-proADM decision algorithm provides cost savings in Spain, Italy, Germany, and the UK.

Economic Analysis of a Ketoanalogue-supplemented Very Low-protein Diet in Patients With Chronic Kidney Disease in Vietnam.

PURPOSE: The aim of this study was to estimate the cost-effectiveness of a very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids compared with a conventional low-protein diet (LPD) in Vietnam. METHODS: The study was conducted from payer (base case), patient, and societal perspectives. A Markov model simulated costs and quality-adjusted life-years (QALYs) for patients with chronic kidney disease stage 4 or 5 (CKD4+) who were followed up during their lifetimes. Patients received a VLPD (0.3- to 0.4-g/kg/d diet) supplemented with ketoanalogues (5 kg/d [1 tablet]) versus LPD (0.6 g/kg/d, mixed proteins). In each model cycle, patient transitions among the health states-CKD4+ (nondialysis), dialysis, and death-were based on transition probabilities taken from the published literature. The time horizon covered the cohort's lifetime. Utilities and costs were estimated from literature review and projected for the lifespan considered in the model. Probabilistic and deterministic sensitivity analyses were performed. FINDINGS: The ketoanalogue-supplemented VLPD increased survival and QALYs compared with the LPD. From a payer's perspective, total cost of care in Vietnam was ₫216,854,268 (€8684/$9242) per patient with LPD versus ₫200,928,819 (€8046/$8563) per patient with a supplemented VLPD (sVLPD) (difference, -₫15,925,449 [-€638/-$679]). From a patient's perspective, total cost of care in Vietnam was ₫217,872,043 (€8724/$9285) per patient with LPD versus ₫116,015,672 (€4646/$4944) per patient with sVLPD (difference, -₫101,856,371 [-€4,079/ -$4341]). From a societal perspective, total cost of care in Vietnam was ₫434,726,312 (€17,408/-$18,527) per patient with LPD versus ₫316,944,491 (€12,692/ $13,508) per patient with sVLPD (difference, -₫117,781,820 [-€4716 €/$5020). IMPLICATIONS: Ketoanalogue-supplemented VLPD lowered costs compared with LPD in all 3 perspectives considered.

Omega-3 fatty acids in parenteral nutrition - A systematic review with network meta-analysis on clinical outcomes.

BACKGROUND & AIMS: Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients. METHODS: MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically combined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes. RESULTS: 1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) = -2.31 (-3.14 to -1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to -1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes. CONCLUSIONS: In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated. REGISTRATION NO: PROSPERO 2022 CRD42022328660.

Economic Analysis of a Ketoanalogue-Supplemented Very Low-Protein Diet in Patients With Chronic Kidney Disease in Taiwan and Thailand.

OBJECTIVE: A vegetarian very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids Ketoanalogue-supplemented very low-protein diet (sVLPD) delays dialysis initiation in patients with chronic kidney disease (CKD). In this cost-effectiveness analysis, we compare an sVLPD with a conventional low-protein diet (LPD) in patients with CKD stage 4-5 using data from Taiwan and Thailand. DESIGN AND METHODS: A Markov model simulated health outcomes and care costs in patients receiving an sVLPD (0.3-0.4 g/kg-day, vegetarian diet) supplemented with ketoanalogues (1 tablet/5 kg-day) or an LPD (0.6 g/kg-day, mixed proteins). Health state transition probability and resource cost inputs were based on published literature and local sources, respectively. RESULTS: An sVLPD increased survival and quality-adjusted life years (QALYs) at a lower cost than an LPD. Total cost of care in Taiwan was 2,262,592.30 New Taiwan dollars (NTD) (68,059.35 EUR) with an LPD and 1,096,938.20 NTD (32,996.18 EUR) with an sVLPD (difference -1,165,654.10 NTD; -35,063.17 EUR). Total cost of care in Thailand was 500,731.09 Thai baht (THB) (14,584.12 EUR) with an LPD and 421,019.22 THB (12,262.46 EUR) with an sVLPD (difference -79,711.86 THB; -2,321.66 EUR). CONCLUSION: A ketoanalogue-supplemented vegetarian sVLPD increased QALYs and lowered lifetime care costs versus an LPD in patients with predialysis CKD in Taiwan and Thailand. These data, together with the new KDOQI Guidelines for nutrition in CKD, support dietary intervention using ketoanalogue-supplemented vegetarian sVLPDs to prevent CKD progression and postpone dialysis as a cost-effective approach, with beneficial effects for patients and health care providers.

Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause.

Background: During SARS-CoV-2 infection, diffuse alveolar damage and pulmonary microvascular abnormalities are critical events that result in gas exchange disorders of varying severity and duration. The only measure of carbon monoxide (CO) diffusing capacity (DLCO) is unable to distinguish the alveolar from the vascular side of present and residual diffusive abnormalities, and measure of nitric oxide (NO) diffusing capacity (DLNO) is also recommended. Dyspnoea, despite being understudied, persists in a significant proportion of patients for several weeks after hospital discharge. The goal of this study was to look into the underlying cause of long-term dyspnoea in patients who were "clinically and radiologically recovered" from COVID pneumonia by assessing DLCO and DLNO at the same time. Methods: Patients of both genders, aged ≥18 years, who had a CT scan showing complete resolution of COVID-related parenchymal lesions were recruited consecutively. Spirometrical volumes, blood haemoglobin, SpO2, DLCO, DLNO and capillary blood volume (Vc) were measured. Data from patients without dyspnoea (group A) and from patients still claiming dyspnoea after 12-16 weeks from their hospital discharge (group B) were statistically compared. Results: Forty patients were recruited: 19 in group A and 21 in group B. Groups were comparable for their general characteristics and spirometrical volumes, that were in the normal range. Mean values for DLCO, DLNO and Vc were significantly and substantially lower than predicted only in patients of group B (p<0.011; p<0.0036; p<0.02; p<0.001, respectively). The DLNO/ DLCO ratio was higher in group B (p<0.001) and inversely correlated to Vc values (-0.3636). Conclusions: The single-breath, simultaneous measurement of DLCO, DLNO, and Vc demonstrated that problems with blood gas exchange can persist even after parenchymal lesions have healed completely. Regardless of the normality of spirometric volumes, there was a significant reduction in lung capillary blood volume. In these patients, the cause of long-term dyspnoea may be related to hidden abnormalities in the vascular side of diffusive function. In the near future, novel therapeutic approaches against residual and symptomatic signs of long-COVID are possible.

Lung Function Can Predict the Expected Inspiratory Airflow Rate through Dry Powder Inhalers in Asthmatic Adolescents.

Several factors affect drug delivery from dry powder inhalers (DPIs). Some are related to patient's physiological characteristics, while others depend on DPIs' technical aspects. The patient's inspiratory airflow rate (IAR) affects the pressure drop and the turbulence needed to disaggregate the powder inside a DPI. The present study investigated whether lung function limitations occurring in asthmatic adolescents affect their IAR when inhaling through a DPI simulator. Eighteen consecutive adolescents with asthma were recruited, and IAR was randomly assessed at low-, mid-, and high-resistance regimens. A multiple logistic model was developed to evaluate the association of patients' lung function characteristics and devices' resistance with the probability to achieve the expected IAR (E-IAR). The mean value of E-IAR achieved seemed to be sex- and age-independent. Low- and high-resistance regimens were less likely to consent the E-IAR level (odds ratio [OR] = 0.035 and OR = 0.004, respectively). Only the basal residual volume and the inspiratory resistance, but not the Forced Expiratory Volume in 1 s (FEV1), seemed to affect the extent of IAR in asthmatic adolescents (OR = 1.131 and OR = 0.290, respectively). The results suggest that the assessment of current lung function is crucial for choosing the proper DPI for asthmatic adolescents.

The Emotional Response to Pandemic of Middle- and High-School Students of an Italian Northern Province: The ERP Study.

The COVID-19 outbreak variably affected people's mental reactions worldwide but was only episodically investigated in healthy Italian teenagers. Our aim was to investigate the emotional responses of Italian middle and high school students to the pandemic. An anonymous 10-item questionnaire was distributed in pre-selected school samples. Responders had to score their perceived extent for each reaction from 0 (lowest perception) to 10 (highest perception). A group of adults was selected as control. Generalized linear models were used to estimate differences among adults and students, high school (HS) and middle school (MS) students, and urban (U) and rural (R) MS students. Comparisons were presented as mean difference (Δ) with a 95% confidence interval (CI). A total of 1512 questionnaires (635 adults, 744 HS, 67 UMS, and 66 RMS) were analyzed. Students appeared more indifferent (Δ = 1.97, 1.52-2.41), anxious (Δ = 0.56, 0.07-1.04), aggressive (Δ = 2.21, 1.72-2.70), and depressed (Δ = 1.87, 1.40-2.34) than adults did, and claimed a higher loss of interest in their activities (Δ = 1.21, 0.72-1.70). Students were less disbelieving (Δ = -0.93, -1.50-0.35) and feared for their loved ones (Δ = -0.89, -1.40-0.39). MS students were less affected by the outbreak than HS students were. Furthermore, R-MS students were significantly less aggressive and depressed, but more indifferent and disbelieving than U-MS. Female sex was an independent factor associated to almost all the questionnaire domains. The pattern of the psychological responses to the pandemic in Italian students proved multifaceted. In addition to anxiety, loss of interest in activities, and depression, aggressiveness emerged as the most characterizing mental attitude in response to the pandemic.

Nebivolol: an effective option against long-lasting dyspnoea following COVID-19 pneumonia - a pivotal double-blind, cross-over controlled study.

Background: Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective ß1 adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via ß3 agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia. Methods: Patients of both genders, aged ≥18 years, non-smokers, who had a CT scan that revealed no COVID-related parenchymal lesions but still complaining of dyspnoea 12-16 weeks after hospital discharge, were recruited. Spirometrical volumes, blood haemoglobin, SpO2, simultaneous diffusing capacity for carbon monoxide (CO) and NO (DLCO and DLNO, respectively), DLNO/DLCO ratio, Vc and exhaled NO (eNO) were measured together with their dyspnoea score (DS), heart frequency (HF), and blood arterial pressure (BAP). Data were collected before and one week after both placebo (P) and nebivolol (N) (2.5 mg od) double-blind cross-over administered at a two-week interval. Data were statistically compared, and p<0.05 assumed as statistically significant. Results: Eight patients (3 males) were investigated. In baseline, their mean DS was 2.5±0.6 SD, despite the normality of lung volumes. DLCO and DLNO mean values were lower than predicted, while mean DLNO/DLCO ratio was higher. Mean Vc proved substantially reduced. Placebo did not modify any variable (all p=ns) while N improved DLco and Vc significantly (+8.5%, p<0.04 and +17.7%, p<0.003, respectively). eNO also was significantly increased (+17.6%, p<0.002). Only N lowered the dyspnoea score (-76%, p<0.001). Systolic and diastolic BAP were slightly lowered (-7.5%, p<0.02 and -5.1%, p<0.04, respectively), together with HF (-16.8%, p<0.03). Conclusions: The simultaneous assessment of DLNO, DLCO, DLNO/DLCO ratio, and Vc confirmed that long-lasting dyspnoea is related to hidden abnormalities in the lung capillary vasculature. These abnormalities can persist even after the complete resolution of parenchymal lesions regardless of the normality of lung volumes. Nebivolol, but not placebo, improves DS and Vc significantly. The mechanism suggested is the NO-mediated vasodilation via the ß3 adrenoceptor stimulation of endothelial NO synthase. This hypothesis is supported by the substantial increase of eNO only assessed after nebivolol. As the nebivolol tolerability in these post-COVID normotensive patients was very good, the therapeutic use of nebivolol against residual and symptomatic signs of long-COVID can be suggested in out-patients.

Comparison of Consistency, Feasibility, and Convenience of a Novel Compact System for Assessing Lung Volumes and Carbon Monoxide Diffusing Capacity versus Whole Body Plethysmography.

BACKGROUND: The MiniBox+™ is an innovative technique for assessing lung volumes (LVs) and the diffusing capacity of the lung for carbon monoxide (DLco). Differently from the equipment needed for whole body plethysmography (WBP), the MiniBox+ is a small, transportable instrument, which derives total lung capacity (TLC) during tidal breathing by analyzing gas pressures and airflows immediately preceding and immediately following airway occlusions. AIM: To compare the consistency and the feasibility of LV and DLco measurements between the two instruments in different lung function disorders, and their cost of execution. METHODS: Consecutive patients of both genders with obstructive and restrictive respiratory disorders were randomly recruited. LVs and DLco were measured by a randomized sequence. The failure risk, number of attempts to achieve the first reliable measurement, corresponding time spent, and costs per patient were compared. RESULTS: A total of 134 patients were enrolled: 42 asthmatics (32.1%), and 47 patients with obstructive (35.1%) and 44 with restrictive respiratory disorders (32.8%). The overall failure risk was 19.4% for WBP and 8.2% for the MiniBox+ (risk ratio=0.417, 95% CI 0.242 to 0.72). LVs and DLco values proved equal with both techniques, regardless of the patients' age, sex, schooling level, and initial lung disorder. Number of attempts and total time spent in achieving the first reliable measurement were significantly lower with the MiniBox+. Mean cost per patient was €87.58 with WBP and €75.11 with the MiniBox+, with a mean saving of €12.33 (95% CI 5.93 to 18.73), mainly due to the saving in productivity loss. CONCLUSION: LV and DLco measurements with the MiniBox+ were highly consistent with those obtained with WBP. The MiniBox+ proved easier to use (lower failure risk) and more convenient (lower execution costs) than WBP.

The contribution of patients' lung function to the inspiratory airflow rate achievable through a DPIs' simulator reproducing different intrinsic resistance rates.

BACKGROUND: The performance of DPIs depends on several physiological (patient-dependent) and technological (device-dependent) factors. The inspiratory airflow rate is the only active force generated and operating in the system for inducing the required pressure drop and eliciting the resistance-induced turbulence needed to disaggregate the powder through the device. The present study aimed to investigate in the most prevalent respiratory disorders whether and at what extent the inspiratory airflow rate achievable when inhaling through a DPIs' simulator reproducing different intrinsic resistance regimens (low, mid, and high resistance) is affected by peculiar changes in lung function and/or can be predicted by any specific lung function parameter. METHODS: The inspiratory airflow rate was assessed in randomized order by the In-Check DIAL G16 at low, mid, and high resistance regimens in a sample of consecutive subjects at recruitment. Independent predictors of the probability to achieve the expected inhalation airflow rate were investigated by means of a multivariate logistic regression model, specific to the disease. RESULTS: A total of 114 subjects were recruited (asthmatics n=30; COPD n=50, restrictive patients n=16, and normal subjects n=18). The mean values of the expected inspiratory airflow rate achieved proved significantly different within the groups (p<0.0001), independently of sex and age. In asthmatics and in COPD patients, the mid-resistance regimen proved highly associated with the highest mean values of airflow rates obtained. Low- and high-resistance regimens were significantly less likely to consent to achieve the expected level of inspiratory airflow rate (OR<1 in all comparisons). Restrictive patients performed the lowest airflow rates at the low-resistance regimen (p<0.01). Unlike FEV1, RV in asthmatics (OR=1.008); RV and IRaw in COPD (OR=0.587 and OR=0.901, respectively), and FIF and TLC in restrictive patients (OR=1.041, and OR=0.962, respectively) proved the only sensitive predictors of the inspiratory airflow rate achievable at the different resistive regimens. CONCLUSIONS: The intrinsic resistive regimen of DPIs can play a critical role. The patients' lung function profile also affects the extent of their inhalation airflow rate. Some specific lung function parameters (such as: FIF; RV; IRaw; TLC, but not FEV1) may be regarded as specific predictors in real-life. In order to optimize the DPI choice, further to the device's technology, also the current patients' lung function should be properly investigated and carefully assessed.

Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma.

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.

Economic impact of mepolizumab in uncontrolled severe eosinophilic asthma, in real life.

BACKGROUND AND AIMS: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients' health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. METHODS: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. RESULTS: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945-2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06-0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15-0.24). CONCLUSIONS: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients' improvement.

A Bayesian Framework to Assess the Usability of Dry Powder Inhalers in a Cohort of Asthma Adolescents in Italy.

The useability of DPIs (dry powder inhalers) depends on several factors that are influenced by the patients' subjectivity and objectivity. The short-form global usability score (S-GUS), a specific tool for the quick ranking and comparison in real life of an inhaler's usability, was used to investigate six of the most prescribed DPIs (Breezhaler, Diskus, Ellipta, Nexthaler, Spiromax, and Turbohaler) in consecutive asthma patients aged <18 years. A Bayesian indirect comparison (IC) was carried out to merge all pairwise comparisons between the six DPIs. Thirty-three subjects participated: eighteen tested Breezhaler, Spiromax, Nexthaler, and Ellipta simultaneously, while fifteen tested Breezhaler, Spiromax, Diskus, and Turbohaler. The estimates of the S-GUS, by the IC model, allowed us to rank the DPIs by their degree of usability: Ellipta, Diskus, and Spiromax were classified as "good to pretty good" (S-GUS > 15), while Spiromax, Turbohaler, and Breezhaler were classified as "insufficient" (S-GUS < 15). The multidomain assessment is recommended in asthma adolescents in order to approximate the effective usability of different DPIs as best as possible. The S-GUS proves particularly suitable in current clinical practice because of the short time required for its use in adolescents.

Assessing the Effect of Nutrition Therapy on Rehospitalization Rate in Malnourished Pediatric Patients With Chronic Diseases.

BACKGROUND: Malnutrition is common among hospitalized children with chronic diseases and increases hospital care needs. The aim of this study is to estimate the clinical consequences of nutrition therapy (NT) after discharge. METHODS: A retrospective analysis of all pediatric inpatients with diagnosis of malnutrition hospitalized at our center from January 2017 to February 2018 was conducted. Malnutrition was assessed according to body mass index (BMI) z-score, routinely recorded in patient's files. The treatment group consists of all patients referred to nutrition assessment and treated by the clinical nutrition team; all the other patients not receiving NT are selected as the control group. The effect of NT on rehospitalization rates, length of stay (LOS), and emergency room (ER) visits was estimated for the total cohort and in a propensity score (PS) matched sample. RESULTS: 277 malnourished pediatric inpatients were enrolled and analyzed. NT was prescribed in 111 patients (40%). Rehospitalization rate was lower in the treated group (rate ratio [RR] = 0.797; 95% CI, 0.630-1.009); particularly, nonelective hospital admissions are considerably lower (RR = 0.556; 95% CI, 0.325-0.952). The strength of this association increased in the PS-matched sample. There is no clear evidence of NT's effect on ER visits (RR = 0.892; 95% CI, 0.580-1.373) or LOS per episode (Δ = 1.46 days; 95% CI, -3.39 to 6.31). CONCLUSIONS: Detecting and treating malnutrition seems to promptly improve the patients' clinical course after discharge, reducing the number of subsequent hospitalizations, particularly nonelective ones, probably caused by unresolved, ongoing malnutrition.

A computational framework for modeling and studying pertussis epidemiology and vaccination.

BACKGROUND: Emerging and re-emerging infectious diseases such as Zika, SARS, ncovid19 and Pertussis, pose a compelling challenge for epidemiologists due to their significant impact on global public health. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to better understand the spreading characteristics of these diseases and to decide on vaccination policies, human interaction controls, and other social measures to counter, mitigate or simply delay the spread of the infectious diseases. Nevertheless, the construction of mathematical models for these diseases and their solutions remain a challenging tasks due to the fact that little effort has been devoted to the definition of a general framework easily accessible even by researchers without advanced modelling and mathematical skills. RESULTS: In this paper we describe a new general modeling framework to study epidemiological systems, whose novelties and strengths are: (1) the use of a graphical formalism to simplify the model creation phase; (2) the implementation of an R package providing a friendly interface to access the analysis techniques implemented in the framework; (3) a high level of portability and reproducibility granted by the containerization of all analysis techniques implemented in the framework; (4) a well-defined schema and related infrastructure to allow users to easily integrate their own analysis workflow in the framework. Then, the effectiveness of this framework is showed through a case of study in which we investigate the pertussis epidemiology in Italy. CONCLUSIONS: We propose a new general modeling framework for the analysis of epidemiological systems, which exploits Petri Net graphical formalism, R environment, and Docker containerization to derive a tool easily accessible by any researcher even without advanced mathematical and computational skills. Moreover, the framework was implemented following the guidelines defined by Reproducible Bioinformatics Project so it guarantees reproducible analysis and makes simple the developed of new user-defined workflows.

The Global Usability Score Short-Form for the simplified assessment of dry powder inhalers (DPIs) usability.

BACKGROUND: The choice of the Dry Powder Inhaler (DPI) to prescribe is a critical issue. The estimation of DPIs usability depends on the objective assessment of several indices related to both subjective and objective determinants. The Global Usability Score (GUS) Questionnaire is a comprehensive tool usable for checking, comparing, and ranking inhalers' usability objectively in real life, but it takes some time to fill. AIM: The aim of this study was to favour the quicker check of DPIs usability in clinical practice by means of a simplified short-form GUS (S-GUS) Questionnaire, while maintaining the high specificity and sensitivity of the original, extended version of the Questionnaire (O-GUS questionnaire). METHODS: The usability of the six most prescribed DPIs was assessed in 222 patients with persistent airway obstruction and needing long-term inhalation treatments. LASSO regression and multicollinearity test were used to select the subset of questions of the O-GUS questionnaire, with the highest information power. Each item was then scored using the corresponding coefficient in the linear regression (normalized at 50 as the O-GUS score). Agreement between the original and the short-form questionnaire was evaluated using the Cohen's kappa statistic (κ). The overall S-GUS values obtained for each DPI were then compared to those from the O-GUS, in the same patients, using a Bayesian indirect comparison (IC) model. RESULTS: After the statistical selection of the items mostly contributing to the overall score, the novel S-GUS questionnaire consists of twelve items only. Nine items are related to patients' opinion before DPIs handling, and three to the nurse's assessment after DPIs practicality. O-GUS and S-GUS score were strongly correlated (R2=0.9843, p<0.0001) and the usability score calculated for each DPI by means of the O- and of S- GUS overlapped almost completely (κ=84.5%, 95% CI 81.3% to 89.2%). Furthermore, S-GUS was much faster to complete than O-GUS (mean time 6.1 vs 23.4 minutes, p<0.001). Estimates of S-GUS, obtained from the IC model, allowed to propose a simple classification of usability: "good" by GUS values >25; "pretty good" by values ≤25≥15, and "insufficient" by values <15. CONCLUSIONS: The S-GUS proves as much specific and suitable as the extended O-GUS questionnaire in measuring DPIs usability, while maintaining the same high sensitivity. As the time required for its use is quite shorter, S-GUS is also particularly suitable and helpful in current clinical practice.

Correction to: Patients' usability of seven most used dry-powder inhalers in COPD.

[This corrects the article DOI: 10.1186/s40248-019-0192-5.].