Real‑life cost and cost‑effectiveness for tiotropium 18 μg od monotherapy in moderate and severe COPD patients: a 48‑month survey

BACKGROUND: Tiotropium monotherapy enables a significant minimization of morbidity in COPD. OBJECTIVE: to evaluate and compare cost and cost‑effectiveness of tiotropium monotherapy administrated for 24 months (18 μg od) in mild‑to‑moderate and severe chronic obstructive pulmonary disease (COPD). METHODS: Clinical outcomes (days in hospital; visits in general ward; cycles of systemic steroids; cycles of antibiotics and maintenance therapy drugs) were evaluated in two groups of patients corresponding to predicted FEV1 baseline values ≤ 50% (A) and > 50% (B) from the Italian NHS perspective. In order to perform cost‑effectiveness analysis, FEV1 value, available for each patient, was converted in SGRQ score using a published multivariate linear model. Utilities were then obtained through the Ståhl equation. RESULTS: The comparison between 24 months of standard therapy and subsequent 24‑month period of tiotropium monotherapy showed that hospitalization cost, which represents the driving treatment cost, drops from 77% to 69% (A) and from 67% to 33% (B) of the total cost. Differently, maintenance therapy cost increased but the amount was more than offset by the savings accruing from the shortening of hospitalization. Furthermore, cost‑effectiveness results revealed a mean savings of about 216 € (A) and 961 € (B) other than a mean gain of 0.07 QALY (A) and 0.02 QALY (B). Dominance of tiotropium (calculated only within patients completing treatment course) revealed that in almost 29% (A) and 36% (B) of subjects tiotropium strategy is dominant while only in 2% (A) and 7% (B) of cases is associated to costs increment and worsening on quality of life. The dominance was systematic in severe COPD. Statistical analyses confirm such trend. CONCLUSIONS: Results of the present study suggest that tiotropium used as unique treatment in COPD systematically consents significant costs savings together with positive effects on evaluated quality. These effects prove proportional to COPD severity.

L’emblema dell’Università di Torino. Storia di un sigillo e delle sue diverse realizzazioni e interpretazioni

The University of Turin embossed emblem even now in use had been rediscovered in 1925. Its origin dates back to 1615 in a wax seal kept in the State Archive of Turin. Since then it has been drawn in different style on official records, diplomas, stamps and academic bulletins. By means of pictures the paper illustrates the history of this emblem from 17th century to 20th century and the symbolic elements which are figured on it (an eagle looking at the sun, a bull, three books and three small marks on each of them). The authors show a new philological interpretation of the Turin University seal which is based not only on the previously mentioned records, but also on the thin, small silver plate emblem recently acquired by the University Historical Archive and on the results of chemical and micromorphological analysis of this find

Prevalence of different comorbidities in COPD patients by gender and GOLD stage

Background: Several comorbidities frequently affect COPD progression. Aim of the study was to assess the prevalence of main comorbidities by gender and disease severity in a cohort of COPD patients referring for the first time to a specialist institution. Methods: The study was a non-interventional, cross-sectional investigation carried out via automatic and anonymous selection from the institutional data base over the period 2012–2015. Inclusion criteria were: subjects of both sex aged ≥40 years; diagnosis of COPD according to GOLD guidelines 2014; the availability of a complete clinical record file. Variables collected were: lung function; smoking history; BMI; the Charlson Comorbidity Index (CCI); number and kind of comorbidities for each patient. Results: At least one comorbidity of clinical relevance was found in 78.6 % of patients, but at least two in 68.8 %, and three or more were found in 47.9 % of subjects. Mean CCI was 3.4 ± 1.6sd. The overall prevalence was 2.6 comorbidities per patient, but 2.5 in males, and 3.0 in females, respectively (p < 0.05). Cardio-vascular disorders were the most frequent, but significantly more frequent in males (44.7 vs 30.7 %, respectively), while the metabolic, the digestive and the osteo-articular disorders were prevailing in females (12.4 vs 9.2; 14.2 vs 4.8, and 6.0 vs 3.8, respectively). In particular, chronic cor pumonale and arrhythmias mainly prevailed in men and congestive heart failure in females, while arterial hypertension resulted equally distributed. As concerning respiratory disorders, pneumonia, pleural effusions and chronic respiratory failure were more frequently found in men, while bronchiectasis and asthma-COPD overlap syndrome (ACOS) in females. Anaemia, gall bladder stones, osteoporosis and spontaneous fractures mostly prevailed in females, while gastric disorders of inflammatory origin and arthrosis were more frequent in males. Cognition disorders, dementia and signs of degenerative brain disorders were more frequently found in men, while depression in females. Finally, lung cancer was at the first place in men, but at the second in females. Conclusions: All comorbidities increased their prevalence progressively up to the last stage of COPD severity, except the cardio-vascular and the metabolic ones which dropped in the IV GOLD stage, presumably due to the high mortality rate in this severe COPD stage. The gender-dependency of comorbidities was confirmed in general terms, even if lung cancer proved a dramatic increase almost independently of sex

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

Introduction: Inhalation devices affect both the effectiveness and the therapeutic outcomes in persistent airway obstruction, and the effects are largely independent of the drug(s) assumed. Usability is a complex and comprehensive indicator of inhalation devices' performance. The Global Usability Score (GUS) Questionnaire is an investigational tool designed to assess objectively the patients'-related and unrelated domains of devices' usability. Methods: The GUS questionnaire was administered to all consecutive COPD patients referring for three months to the Lung Unit of CEMS Specialist Centre (Verona, Italy). The usability of seven Dry Powder Inhalers (DPIs) indicated as appropriate in COPD was tested and compared: Breezhaler, Diskus, Ellipta, Genuair, Nexthaler, Spiromax, and Turbohaler. Patients were divided in two groups, checked separately, according to their DPIs previous experience. A Bayesian Indirect Comparison (IC) model was built to assess "global usability" ranking. Results: A total of 103 patients were investigated: 74 patients already instructed in DPI use and 29 naive to DPIs. IC analysis proved Ellipta as the device characterized by the highest usability, while Breezhaler the device with the lowest usability in both groups of COPD patients (both with probability > 90%). Moreover, Turbohaler ranked second according to the Bayesian pooling, followed by Diskus, Spiromax, Nexthaler, and Genuair in patients already instructed in DPI use, while the ranking order was not as much well defined in naïve patients, likely due to their too small sample. Conclusions: Usability is a multifaceted indicator that contributes to assess the factual DPIs' convenience in real life. DPIs are characterized by different levels of real-life usability, which can be checked, compared and ranked by means of the GUS score

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

SummaryBronchial 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 €290.4 (interquartile range—iqr 32.8) in atopic and €438.4 (iqr 27.8) in GER-related asthma (p<0.001); expenditure for medical consultations and diagnostics were €166.1 (iqr 14.8) vs. €71.6 (iqr 11.0) (p<0.001), and €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. €567.1±11.0 (p<0.001), and €748.7±94.7 vs. €103.6±33.9 (p<0.001), respectively. The total annual cost per patient was €1246.7 (iqr 1979.6) in atopic and €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

p130Cas promotes invasiveness of three dimensional ErbB2-transformed mammary acinar structures by enhanced activation of mTOR/p70S6K and Rac1

ErbB2 over-expression is detected in approximately 25% of invasive breast cancers and is strongly associated with poor patient survival. We have previously demonstrated that p130Cas adaptor is a crucial mediator of ErbB2 transformation. Here, we analysed the molecular mechanisms through which p130Cas controls ErbB2-dependent invasion in three-dimensional cultures of mammary epithelial cells. Concomitant p130Cas over-expression and ErbB2 activation enhance PI3K/Akt and Erk1/2 MAPK signalling pathways and promote invasion of mammary acini. By using pharmacological inhibitors, we demonstrate that both signalling cascades are required for the invasive behaviour of p130Cas over-expressing and ErbB2 activated acini. Erk1/2 MAPK and PI3K/Akt signalling triggers invasion through distinct downstream effectors involving mTOR/p70S6K and Rac1 activation, respectively. Moreover, in silico analyses indicate that p130Cas expression in ErbB2 positive human breast cancers significantly correlates with higher risk to develop distant metastasis, thus underlying the value of the p130Cas/ErbB2 synergism in regulating breast cancer invasion. In conclusion, high levels of p130Cas favour progression of ErbB2-transformed cells towards an invasive phenotype