The economic impact of biosimilars in Italy : a scenario analysis

Background: the first generation of biotechnology drugs is reaching, or has already reached, the patent expiry and a large number of biosimilars is entering the Italian pharmaceutical market. The objective of the analysis was to evaluate the economic impacts of biosimilars on the national health expenditure in Italy between 2014 and 2020. Methods: Based on the information deriving from consumption per standard unit and equivalent patients, it was estimated monthly expenditure for some of the biological drugs currently available in Italy that have had or will have a patent expiry within the analysis period (infliximab, etanercept, adalimumab, insulin glargine, trastuzumab, rituximab, bevacizumab and insulin aspart). Pharmaceutical expenditure was calculated on hospital sales prices net of transparent discounts required by law and visible from the AIFA database. Three alternative scenarios have been developed based on the perceptions of a board of clinical experts, pharmacologists and pharmacoeconomists involved in the study. The experts involved analyzed the estimates of treated patients between 2014 and 2017 and reports their hypothetical biosimilar penetration during the period 2018-2020. The results were represented as the difference between the estimated expenditure in the absence of biosimilars and the estimated expenditure in the presence of biosimilars with the real or hypothetical biosimilar penetration. Results: considering the standard units dispensed for each year, the economic model estimate an annual expenditure in 2014 equal to € 1.47 billion for the molecules considered in the analysis. These estimates rise to € 1.54, € 1.50 billion and € 1.51 billion during 2015, 2016 and 2017 in the scenario without biosimilar introduction. Biosimilar introduction generates cost savings between € 3.8 million in 2015 and € 32.9 million in 2017 if compared with the scenario without. Assuming an increasing biosimilar penetration between 2018 and 2020, scenario analysis estimates a cumulative cost reduction equal to € 597 million. Conclusions: Overall, biosimilar penetration generates important cost reduction that could be re-invested in the National Health Sistem

Effects of synchronous music on treadmill running among elite triathletes

Research has shown that running in time to music that is synchronized to stride rate can provide significant benefits for sub-elite athletes, although it is uncertain whether such benefits also accrue for elite performers. The present study evaluated the effects of running in time to music on a treadmill using a range of psychological, physiological and performance indices among a sample of elite triathletes. An initial test was conducted to establish aerobic capacity and individual stride rates at various running speeds. Triathletes were presented with music selections of appropriate tempi for each running speed (i.e., synchronous music), and chose tracks they considered to be (a) motivational, and (b) neutral. They then completed a standardised running test on three occasions in counterbalanced order under three conditions (no-music, motivational music, neutral music). The test protocol involved a warm-up, three 4-minute periods of steady state running at progressively faster velocities, followed by a run-to-exhaustion at approximately 110% of blood lactate threshold. Dietary intake was controlled over the day preceding each test. Measures were taken after each 4-minute period of steady state running and after the run-to-exhaustion for (a) perceived exertion using the Borg Scale; (b) psychological state using the Feeling Scale; (c) oxygen utilization; and (d) blood lactate. Time to exhaustion was recorded and mood responses were assessed prior to and following each test, using the Brunel Mood Scale. Perceived exertion was lower with music than without music even though the same amount of work was completed. Feelings remained more positive throughout the test with motivational music compared to neutral music and no-music. Oxygen consumption was about 3% lower when running in time to music compared to running without music, although blood lactate levels remained almost identical. Compared to the no-music condition, time-toexhaustion improved by more than 12% when running in time to music. Mood responses were more positive with music. Results confirmed the hypothesized benefits of music but suggested that synchronicity of the music to the activity may be more important in functional terms than the motivational qualities of the music

Ergogenic, psychological, and psychophyiological effects of synchronous music on treadmill running

Music has been shown to exert various ergogenic (i.e., work-enhancing), psychological (e.g., improved mood), and psychophysical (i.e., lowered perceptions of exertion) benefits during physical activity.When movements are performed in synchrony with music, some of the benefits (e.g., work-enhancement) appear to be amplified (see e.g., Karageorghis, Mouzourides, Priest, Sasso, Morrish, & Whalley, 2009).To further develop the train of research on synchronous music and to extend it to elite athletes, the present study utilised a sample of Australian triathletes (N = 11) who were exposed to either self-selected motivational music, a neutral equivalent (in terms of its motivational qualities), or a no-music control during steady-state and exhaustive treadmill running.The measured variables were work output (aerobic endurance), psychological (mood states, feeling states), psychophysical (RPE scale), and physiological (blood lactate, oxygen consumption, metabolic efficiency). Both music conditions, in particular the motivational selection, were found to exert consistent benefits across each dependent measure when compared to the no-music control. Notably, feeling states remained more positive throughout the test in the motivational music condition when compared to the other conditions. However, the differences in endurance between motivational and neutral music conditions were negligible, indicating that that music's affective/aesthetic qualities are of lesser importance when used synchronously. The present findings also indicate that both music conditions enhanced metabolic efficiency to a degree that implies a practical value at the highest levels of competition. Guidelines will be offered to facilitate the application of synchronous music among elite endurance athletes

[Characteristics and effectiveness of smoking cessation programs in Italy. Results of a multicentric longitudinal study]

Aim: to describe the characteristics and effectiveness of various smoking cessation programs offered by Italian treatment services operating within the National Health Service. Design: prospective longitudinal multicentre study involving 41 smoking cessation services in 16 Italian regions. Study population: the study population includes patients entering smoking cessation programs between April 2003 and June 2004. The "study population" includes 1226 patients (54.2% males and 45.4% females), mean age 47 years. Patients have a middle/high level of education and a long history of smoking; most are highly dependent on nicotine and report previous attempts to quit smoking. Methods: treatment effectiveness in smoking cessation is assessed six months after entering treatment service. Logistic Regression Model was used to determine the predictors of successfiul cessation, independent of treatment typology. The predictors were included as confounding variables in the logistic regression model that was used to evaluate the effectiveness of treatments. Besides the effect of treatment completion on smoking cessation was estimated. Results: predictors of successful smoking cessation are: being male, presence of a partner, strong motivation to quit, previous attempts to give up smoking, mild nicotine dependence, and not suffering from mood disturbances. All treatments are effective in helping people to stop smoking: cessation rate ranges between 25.00% for patients receiving a single session of motivational counselling and 65.3% for those receiving nicotine replacement therapy combined to group therapy. Compared to a single session of motivational counseling, nicotine replacement therapy combined to group therapy is the most effective therapeutic program (OR 5.4; 95%CI 12.5-12.0). Treatment completion is a strong determinant ofsuccess (OR 4.8; 95%CI 3.5-6.4). Conclusion: enrolling people in any type of therapeutic program, in particular nicotine replacement therapy combined with group therapy increases the probability of successfully quitting smoking; moreover, patients that begin a smoking cessation program should be encouraged to complete the therap

L’attività dei Centri Antifumo italiani tra problematiche e aree da potenziare: i risultati di un’indagine svolta attraverso un questionario on-line

Introduzione. In Italia sono 295 i Servizi per la cessazione dal fumo di tabacco (Centri Antifumo - CA) afferenti al Servizio Sanitario Nazionale (SSN) censiti nel 2011 dall’Osservatorio Fumo, Alcol e Droga (OssFAD) dell’Istituto Superiore di Sanità. La presente indagine, condotta dall’OssFAD in collaborazione con i CA, è stata volta a rilevare alcune delle problematiche con le quali il personale dei CA si confronta per portare avanti la propria attività e le iniziative ritenute utili per migliorarla. Materiali e metodi. L’indagine è stata condotta dal 7 al 21 maggio 2012, mediante un questionario compilabile on-line composto da 5 brevi sezioni di domande con un totale di 38 items da completare. Il link al questionario on-line è stato inviato per e-mail a 322 indirizzi dei CA censiti nel 2011 dall’OssFAD. I dati raccolti sono stati elaborati statisticamente con il programma SPSS 20. Risultati. All’indagine hanno risposto 146 operatori dei CA (45,3%). Sebbene ci siano aspetti ormai consolidati dell’attività dei CA, sono ancora molte le criticità che gli operatori riscontrano nella loro attività. Le principali problematiche che influiscono in modo fondamentale/rilevante per la buona attività del centro sono le “Scarse o nulle risorse economiche” per il 60,7% del personale, “la mancanza di personale dedicato” per il 52,4% del personale; il “riconoscimento/mandato istituzionale del CA” per il 40,9% del personale. Tra le azioni ritenute più efficaci per facilitare l’accesso ai CA sono risultate la sensibilizzazione del personale sanitario (91%), in particolare dei medici di famiglia e l’inserimento delle prestazioni antitabagiche nei LEA (76,8%). Conclusioni. È auspicabile che l’attività dei CA riceva una maggiore attenzione, attraverso la dotazione di strutture, personale e finanziamenti adeguati a svolgere un importante ruolo nella tutela e promozione della salute

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old