Costs of chronic obstructive pulmonary disease (COPD) in Italy: The SIRIO study (Social Impact of Respiratory Integrated Outcomes)

SummaryChronic respiratory diseases affect a large number of subjects in Italy and are characterized by high socio-health costs. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and costs generated in 1 year by a population of patients with chronic obstructive pulmonary disease (COPD) in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data from COPD patients who reported spontaneously to pneumological centers participating in the study, the corresponding economic outcomes being assessed at baseline and after a 1-year survey. A total of 748 COPD patients were enrolled, of whom 561 [408m, mean age 70.3 years (SD 9.2)] were defined as eligible by the Steering Committee. At the baseline visit, the severity of COPD (graded according to GOLD 2001 guidelines) was 24.2% mild COPD, 53.7% moderate and 16.8% severe. In the 12 months prior to enrollment, 63.8% visited a general practitioner (GP); 76.8% also consulted a national health service (NHS) specialist; 22.3% utilized Emergency Care and 33% were admitted to hospital, with a total of 5703 work days lost. At the end of the 1-year survey, the severity of COPD changed as follows: 27.5% mild COPD, 47.4% moderate and 19.4% severe. Requirement of health services dropped significantly: 57.4% visited the GP; 58.3% consulted an NHS specialist; 12.5% used Emergency Care and 18.4% were hospitalized. Compared to baseline, the mean total cost per patient decreased by 21.7% (p<0.002). In conclusion, a significant reduction in the use of health resources and thus of COPD-related costs (both direct and indirect costs) was observed during the study, likely due to a more appropriate care and management of COPD patients

Use of aerosols in bronchiectasis patients

Bronchiectasis is a chronic respiratory disease which recognises different etiologies, and characterised by persistent cough, bronchial hypersecretion, airway colonisation with Gram-negative pathogens; frequent infectious exacerbations; progressive lung function decline, and poor quality of life. Several therapeutic strategies are used for managing bronchiectasis, and nebulised medications are regarded with great and ever increasing interest because they allow the direct medication of targets airway structures, higher concentrations of the drug employed, and much less systemic effects. In general terms, the available therapeutic strategies lead to different results depending of whether bronchiectasis are related to cystic fibrosis or not. The effects of the main classes of drugs for aerosol delivery in bronchiectasis patients have been reviewed and updated. Further research is needed in order to ameliorate therapeutic interventions in bronchiectasis, both in terms of new molecules and aerosol formulations to use, and of systems able to optimize drug delivery and drug effectiveness

Disruption of smooth pursuit eye movements in cirrhosis: relationship to hepatic encephalopathy and its treatment.

Smooth pursuit eye movements (SPEM) are the conjugate movements used to track the smooth trajectory of small dots. Jerky or 'saccadic' ocular pursuit has been reported in patients with cirrhosis, but no formal assessment of SPEM has ever been undertaken. The aim of this study was to evaluate SPEM in patients with cirrhosis and varying degrees of hepatic encephalopathy. The patient population comprised 56 individuals (31 men, 25 women) of mean age 51.1 (range, 25-70) years, with biopsy-proven cirrhosis, classified, using clinical, electroencephalographic, and psychometric variables, as either neuropsychiatrically unimpaired or as having minimal or overt hepatic encephalopathy; patients were further categorized in relation to their treatment status. The reference population comprised 28 healthy volunteers (12 men, 16 women) of mean age 47.3 (range, 26-65) years. SPEM was assessed using an electro-oculographic technique. Visual inspection of the SPEM recordings showed clear disruption of smooth pursuit in the patients with minimal hepatic encephalopathy, and more pronounced disruption, if not complete loss, of smooth pursuit in patients with overt hepatic encephalopathy. The differences observed in quantifiable SPEM indices between the healthy volunteers/unimpaired patients and those with overt hepatic encephalopathy were significant (P < .05). In conclusion, SPEM performance is impaired in patients with hepatic encephalopathy in parallel with the degree of neuropsychiatric disturbance: the pathophysiology of these changes is unknown, but retinal, extrapyramidal, and attentional abnormalities are likely to play a role. Treatment status confounds the classification of neuropsychiatric status and should be taken into account when categorizing these patients

Prevalence of severe asthma according to the drug regulatory agency perspective: An Italian experience

Severe asthma prevalenc

A MCh test pre-post esophageal acidification in detecting GER-related asthma.

Abstract The direct effect of gastro-esophageal reflux (GER) on lung function is still debated. Objective. To investigate the role of esophageal acidification in affecting airway response to MCh in GER-related versus atopic asthmatics and to assess specificity and sensitivity of events. Subjects. A total of 56 never-smoking, mild asthmatics: 27 non-atopic asthmatics and acid GER (GER+ve) and 29 atopic asthmatics without any GER (GER-ve). Methods. Each subject performed an MCh challenge in baseline (MCh(b)), and 30 minutes after an acid drink (125 mL at pH = 2; MCh(ac)), one day apart. PD(20)FEV(1) MCh(b) and MCh(ac) were compared by estimating the area under the ROC curve (AU-ROC). Results. GER+ve and GER-ve subjects (well matched in baseline) had a different duration of esophageal acid contact (24-hour monitoring; pH-24h AU(4)), and PD(20)FEV(1) MCh(ac) (both p < 0.001). AU-ROC was 86.3% (76% to 97%, 95%CI). Sensitivity and specificity of changes were 82.8% (72.9% to 92.7%, 95%CI) and 85.2% (75.9% to 94.5%, 95%CI), respectively. The difference in MCh threshold that maximized both the sensitivity and specificity level was 100 mu g. Conclusions. The esophageal acidification identified GER-related asthma with a good level of both sensitivity and specificity by enhancing the MCh response only in the presence of acid GER. Data are supporting the effectiveness of this procedure for clinical purposes

Changes in total IgE plasma concentration measured at the third month during anti-IgE treatment predict future exacerbation rates in difficult-to-treat atopic asthma: a pilot study.

Abstract In severe, difficult-to-treat atopic asthma with sensitization to perennial allergens, monoclonal antibodies directed against immunoglobulin E (IgE) are recognized to be clinically effective. Omalizumab, a recombinant monoclonal antibody, selectively binds to the high-affinity C-epsilon 3 site of human IgE and inhibits the inflammatory cascade in response to antigenic stimuli. Currently, no indicator is available for predicting patients' responsiveness to long-term omalizumab treatment. This study aims to assess the relationship between early changes in plasma IgE concentration and major outcome variables over a 12-month course of omalizumab. METHODS: Twenty-three nonsmoking, severe asthmatics (14 females; mean age 47.3 years \ub1 12.0 SD; mean BMI 25.8 kg/m(2) \ub1 9.6 SD) sensitized to perennial allergens and unresponsive to high doses of common therapies were evaluated during a 12-month period of omalizumab treatment. Variables included total IgE plasma concentrations, Forced Expiratory Volume 1 second (FEV(1)) symptom complaints (Asthma Control Test (ACT) score), number of emergency visits, hospitalizations, and exacerbations. The Wilcoxon signed-rank test was used to compare changes observed after the 1-year omalizumab treatment versus baseline. Statistical modelization was used to determine possible relationships between changes in outcomes after 12 months and early changes in plasma IgE (after 3 months of treatment). RESULTS: The number of emergency visits, hospitalizations, and exacerbations decreased (p < .004, p < .001, and p < .001, respectively) over the 12-months. In contrast, FEV(1) and ACT score substantially increased (both p < .001); the ACT score reaching maximum after only 3 months. The S model showed the best fit and proved the strict relationship between the increase in IgE after 3 months and the exacerbation rate over the 1-year survey (threshold value of 65250 IU/ml, p < .001). The improvement in FEV(1) was independent of the increase in IgE. CONCLUSIONS: When confirmed on a larger population, early changes in IgE may be used as a predictor of future responders to omalizumab in terms of exacerbation rate, thus minimizing the economic burden of anti-IgE therapy

Diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias

PURPOSE Inguinal hernias are mainly diagnosed clinically, but imaging can aid in equivocal cases or for treatment planning. The purpose of this study was to evaluate the diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias. METHODS This single-center retrospective study reviewed all consecutive Valsalva-CT studies between 2018 and 2019. A composite clinical reference standard including surgery was used. Three blinded, independent readers (readers 1-3) reviewed the CT images and scored the presence and type of inguinal hernia. A fourth reader measured hernia size. Interreader agreement was quantified with Krippendorff's α coefficients. Sensitivity, specificity, and accuracy of Valsalva-CT for the detection of inguinal hernias was computed for each reader. RESULTS The final study population included 351 patients (99 women) with median age 52.2 years (interquartile range (IQR), 47.2, 68.9). A total of 381 inguinal hernias were present in 221 patients. Sensitivity, specificity, and accuracy were 85.8%, 98.1%, and 91.5% for reader 1, 72.7%, 92.5%, and 81.8% for reader 2, and 68.2%, 96.3%, and 81.1% for reader 3. Hernia neck size was significantly larger in cases correctly detected by all three readers (19.0 mm, IQR 13, 25), compared to those missed by all readers (7.0 mm, IQR, 5, 9; p < 0.001). Interreader agreement was substantial (α = 0.723) for the diagnosis of hernia and moderate (α = 0.522) for the type of hernia. CONCLUSION Valsalva-CT shows very high specificity and high accuracy for the diagnosis of inguinal hernia. Sensitivity is only moderate which is associated with missed smaller hernias

Cost analysis of GER-induced asthma: a controlled study vs. atopic asthma of comparable severity.

Abstract Bronchial asthma is a costly disease: while the role of pharmaceutical strategies was greatly emphasised in order to alleviate its economic burden,the aetiological approach to asthma has received much less attention from this point of view. The impact of gastro-oesophageal reflux (GER)-related asthma was assessed in comparison to atopic asthma in 262 matched patients,and the corresponding direct and indirect annual costs calculated. All subjects were screened by means of a 95-item self-questionnaire. The overall resource utilisation was calculated for the last 12 months. Drug-induced annual costs were euro 290.4 (interquartile range-iqr 32.8) in atopic and euro 438.4 (iqr 27.8) in GER-related asthma (p<0.001); expenditure for medical consultations and diagnostics were euro 166.1 (iqr 14.8) vs. euro 71.6 (iqr 11.0) (p<0.001),and euro 338.4 (20.0) vs. 186.9 (iqr 26.5) (p<0.001),respectively. Direct costs due to hospital admissions and indirect costs due to absenteeism were also higher in GER-related asthmatics: 2.201.7+/-90.0 vs. euro 567.1+/-11.0 (p<0.001),and euro 748.7+/-94.7 vs. euro 103.6+/-33.9 (p<0.001),respectively. The total annual cost per patient was euro 1246.7 (iqr 1979.6) in atopic and euro 3967.1 (iqr 3751.5) in GER-related asthma,p<0.001. In conclusion,GER-induced asthma has a more relevant economic impact on healthcare resources than atopic asthma. Although further studies are needed,present data tend to demonstrate that when facing difficult asthma (GER-related asthma in this case),the aetiological assessment of the disease plays a critical role in optimising the approach to patients' needs

Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation

Background. Pulmonary Rehabilitation ("Rehabilitation") can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease (COPD) even if only a very small proportion of patients have access to Rehabilitation. Supplementation of Essential Amino Acids (EAAs) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status. Methods. 88 COPD out-patients (GOLD class 3-4) with a body mass index (BMI) &lt;23 Kg/m2 were randomised to receive EAAs (n=44) or placebo (n=44) for twelve weeks. Primary outcome measures were changes in both physical activities in daily life (measured by Sense Wear Armband in terms of mean steps walked in one week) and in quality of life (measured by the St George's Respiratory Questionnaire, SGRQ). Results. After 12 weeks, the physical performance was significantly increased vs baseline only in patients who received EAAs (1140.33 ± 524.69 and 638.68 ± 662.1 steps/day, respectively; p=0.02), being also the comparison vs the placebo group highly significant (p=0.003). Similarly, the SGRQ score improved significantly only in EAA patients (69.35 ± 9.51 vs baseline 72.04 ± 8.62; p&lt;0.01), and changes were significantly different from those measured in the placebo group (p&lt;0.001). Furthermore, when compared to those who received placebo, EAAs patients significantly increased their fat-free mass (p=0.04), muscle strength (p&lt;0.01), saturation of oxygen (p=0.05), serum albumin (p&lt;0.001), and also ameliorated their original cognitive dysfunction (p=0.02). Conclusions. Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme, together with their quality of life; nutritional and cognitive status, and muscle strength

Drop-out rate among patients treated with omalizumab for severe asthma: Literature review and real-life experience

BACKGROUND: In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database. RESULTS: In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals. CONCLUSIONS: Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice