Are prescribing doctors sensitive to the price that their patients have to pay in the Spanish National Health System?

[EN] Background This study aims to design an empirical test on the sensitivity of the prescribing doctors to the price afforded for the patient, and to apply it to the population data of primary care dispensations for cardiovascular disease and mental illness in the Spanish National Health System (NHS). Implications for drug policies are discussed. Methods We used population data of 17 therapeutic groups of cardiovascular and mental illness drugs aggregated by health areas to obtain 1424 observations ((8 cardiovascular groups * 70 areas) + (9 psychotropics groups * 96 areas)). All drugs are free for pensioners. For non-pensioner patients 10 of the 17 therapeutic groups have a reduced copayment (RC) status of only 10% of the price with a ceiling of €2.64 per pack, while the remaining 7 groups have a full copayment (FC) rate of 40%. Differences in the average price among dispensations for pensioners and non-pensioners were modelled with multilevel regression models to test the following hypothesis: 1) in FC drugs there is a significant positive difference between the average prices of drugs prescribed to pensioners and non-pensioners; 2) in RC drugs there is no significant price differential between pensioner and non-pensioner patients; 3) the price differential of FC drugs prescribed to pensioners and non-pensioners is greater the higher the price of the drugs. Results The average monthly price of dispensations to pensioners and non-pensioners does not differ for RC drugs, but for FC drugs pensioners get more expensive dispensations than non-pensioners (estimated difference of €9.74 by DDD and month). There is a positive and significant effect of the drug price on the differential price between pensioners and non-pensioners. For FC drugs, each additional euro of the drug price increases the differential by nearly half a euro (0.492). We did not find any significant differences in the intensity of the price effect among FC therapeutic groups. Conclusions Doctors working in the Spanish NHS seem to be sensitive to the price that can be afforded by patients when they fill in prescriptions, although alternative hypothesis could also explain the results found.

Studio delle proprietà oncotiche e non incotiche dell'albumina nel paziente con cirrosi epatica e ascite

L’albumina umana (HA) è usata per le sue proprietà oncotiche per ricostituire il volume circolante in pazienti critici e nella cirrosi epatica avanzata. Tuttavia, l’albumina non è solo semplice espansore plasmatico, ma è provvista anche di proprietà non oncotiche, quali, la capacità di legare e trasportare molecole insolubili in acqua, come metalli e farmaci, il suo potere antiossidante e di detossificazione di sostanze sia endogene che esogene. Il nostro studio, è stato progettato da un lato per dimostrare che il trattamento in cronico con albumina umana nei pazienti cirrotici con ascite è in grado di ridurre l’incidenza di ascite refrattaria, delle complicanze legate all’uso dei diuretici e la ricorrenza delle ospedalizzazioni (studio randomizzato), dall’altro per determinare se le alterazioni delle proprietà non oncotiche dell’albumina, possono rappresentare degli indicatori di un aumentato rischio di complicanze cliniche e di una prognosi sfavorevole di questi pazienti (studio di coorte). METODI Studio multicentrico, prospettico, randomizzato, in 440 pts cirrotici con ascite: due bracci di trattamento: t. medica standard vs t. medica standard + albumina; Studio di coorte con 110 cirrotici vs 50 individui sani, valutati mediante -analisi proteomica per individuare con le modifiche post-trascrizionali; - Cobalt Binding Albumina (ACB) per quantificare la quota di albumina modificata dall’ischemia e IMA-Ratio. RISULTATI Studio randomizzato: non è possibile trarre conclusioni, ma emerge un dato incoraggiante, cioè i pazienti del braccio standard hanno una maggiore tendenza a chiudere lo studio per tre paracentesi / mese; Studio Coorte:-IMA e IMA-R sono aumentati in cirrosi, ma non associate a complicanze della cirrosi, l'infezione batterica è associata ad un aumento IMA e IMA-R in cirrosi. CONCLUSIONE: Lo studio randomizzato è in corso ma i dati preliminari sono incoraggianti. Lo studio coorte, ha dimostrato che la cirrosi è associata da alterazioni post-trascrizionali che coinvolgono il N-terminale ed i siti di legame Cys-34.

Efficient ultrasonic signal processing techniques for aided medical diagnostics

Ultrasound imaging is widely used in medical diagnostics as it is the fastest, least invasive, and least expensive imaging modality. However, ultrasound images are intrinsically difficult to be interpreted. In this scenario, Computer Aided Detection (CAD) systems can be used to support physicians during diagnosis providing them a second opinion. This thesis discusses efficient ultrasound processing techniques for computer aided medical diagnostics, focusing on two major topics: (i) Ultrasound Tissue Characterization (UTC), aimed at characterizing and differentiating between healthy and diseased tissue; (ii) Ultrasound Image Segmentation (UIS), aimed at detecting the boundaries of anatomical structures to automatically measure organ dimensions and compute clinically relevant functional indices. Research on UTC produced a CAD tool for Prostate Cancer detection to improve the biopsy protocol. In particular, this thesis contributes with: (i) the development of a robust classification system; (ii) the exploitation of parallel computing on GPU for real-time performance; (iii) the introduction of both an innovative Semi-Supervised Learning algorithm and a novel supervised/semi-supervised learning scheme for CAD system training that improve system performance reducing data collection effort and avoiding collected data wasting. The tool provides physicians a risk map highlighting suspect tissue areas, allowing them to perform a lesion-directed biopsy. Clinical validation demonstrated the system validity as a diagnostic support tool and its effectiveness at reducing the number of biopsy cores requested for an accurate diagnosis. For UIS the research developed a heart disease diagnostic tool based on Real-Time 3D Echocardiography. Thesis contributions to this application are: (i) the development of an automated GPU based level-set segmentation framework for 3D images; (ii) the application of this framework to the myocardium segmentation. Experimental results showed the high efficiency and flexibility of the proposed framework. Its effectiveness as a tool for quantitative analysis of 3D cardiac morphology and function was demonstrated through clinical validation.

Musculoskeletal tissue regeneration by human non-embryonic stem cells

The aim of this thesis was to investigate the regenerative potential of alternative sources of stem cells, derived from human dental pulp (hDPSCs) and amniotic fluid (hAFSCs) and, specifically, to evaluate their capability to be committed towards osteogenic and myogenic lineages, for the eventual applicability of these stem cells to translational strategies in regenerative medicine of bone and skeletal muscle tissues. The in vitro bone production by stem cells may represent a radical breakthrough in the treatment of pathologies and traumas characterized by critical bone mass defects, with no medical or surgical solution. Human DPSCs and AFSCs were seeded and pre-differentiated on different scaffolds to test their capability to subsequently reach the osteogenic differentiation in vivo, in order to recover critical size bone defects. Fibroin scaffold resulted to be the best scaffold promoting mature bone formation and defect correction when combined to both hDPSCs and hAFSCs. This study also described a culture condition that might allow human DPSCs to be used for human cell therapy in compliance with good manufacturing practices (GMPs): the use of human serum (HS) promoted the expansion and the osteogenic differentiation of hDPSCs in vitro and, furthermore, allowed pre-differentiated hDPSCs to regenerate critical size bone defects in vivo. This thesis also showed that hDPSCs and hAFSCs can be differentiated towards the myogenic lineage in vitro, either when co-cultured with murine myoblasts and when differentiated alone after DNA demethylation treatment. Interestingly, when injected into dystrophic muscles of SCID/mdx mice - animal model of Duchenne Muscular Dystrophy (DMD) - hDPSCs and hAFSCs pre-differentiated after demethylating treatment were able to regenerate the skeletal muscle tissue and, particularly, to restore dystrophin expression. These observations suggest that human DPSCs and AFSCs might be eventually applied to translational strategies, in order to enhance the repair of injured skeletal muscles in DMD patients.

Skin tissue engineering: medical problems and technological solutions.

In questo elaborato si affrontano problematiche cliniche legate ai traumi gravi della cute in cui è necessario intervenire chirurgicamente per ripristinare una situazione normale: si approfondisce lo studio della fisiologia del tessuto, la classificazione dei gradi delle ustioni della pelle, la guarigione delle ferite e la meccanica della cute. Il trapianto di tessuto autologo costituisce la soluzione più efficace e con minori complicazioni. Tuttavia il paziente potrebbe non presentare una superficie di cute disponibile sufficientemente estesa, per cui si ricorre ad altri metodi. In primo luogo, si effettuano degli allotrapianti di tessuto di donatore cadavere prelevati secondo le normative vigenti e conservati attraverso le varie tecniche, il cui sviluppo ha consentito una durata di conservazione maggiore; mentre la glicerolizzazione abbatte al 100% il rischio di trasmissione di patologie e lo sviluppo di microorganismi, la crioconservazione preserva la vitalità del tessuto. La chirurgia utilizzata per queste operazioni si avvale di tecnologie innovative come la Tecnologia a Pressione Negativa. Un'alternativa necessaria per sopperire all'ingente richiesta di tessuto di donatore sono i sostituti cutanei, che presentano un grande potenziale per il futuro. Per eliminare totalmente il rischio di rigetto sarebbe necessario personalizzare il costrutto utilizzando cellule autologhe, ma la ricerca è stata rallentata da minori investimenti da parte dell'industria biomedica, che si è maggiormente focalizzata sulla realizzazione di prodotti utilizzabili da un più ampio raggio di pazienti. Per queste ragioni, l'ingegneria tissutale della cute ha trovato più ampio campo di applicazione nel sistema dei test in vitro. A tale scopo sono stati creati dei protocolli certificati per testare la corrosività, la irritabilità e la vitalità del tessuto cutaneo, quali EpiDerm, EpiSkin e SkinEthic che si avvalgono dell'uso del metodo MMT e della spettrofotometria, che è diventata un supporto fondamentale per le scienze biologiche.

Advanced aspects of radiation protection in the use of particle accelerators in the medical field

In this work, the well-known MC code FLUKA was used to simulate the GE PETrace cyclotron (16.5 MeV) installed at “S. Orsola-Malpighi” University Hospital (Bologna, IT) and routinely used in the production of positron emitting radionuclides. Simulations yielded estimates of various quantities of interest, including: the effective dose distribution around the equipment; the effective number of neutron produced per incident proton and their spectral distribution; the activation of the structure of the cyclotron and the vault walls; the activation of the ambient air, in particular the production of 41Ar, the assessment of the saturation yield of radionuclides used in nuclear medicine. The simulations were validated against experimental measurements in terms of physical and transport parameters to be used at the energy range of interest in the medical field. The validated model was also extensively used in several practical applications uncluding the direct cyclotron production of non-standard radionuclides such as 99mTc, the production of medical radionuclides at TRIUMF (Vancouver, CA) TR13 cyclotron (13 MeV), the complete design of the new PET facility of “Sacro Cuore – Don Calabria” Hospital (Negrar, IT), including the ACSI TR19 (19 MeV) cyclotron, the dose field around the energy selection system (degrader) of a proton therapy cyclotron, the design of plug-doors for a new cyclotron facility, in which a 70 MeV cyclotron will be installed, and the partial decommissioning of a PET facility, including the replacement of a Scanditronix MC17 cyclotron with a new TR19 cyclotron.

Information and communication technologies nella gestione integrata del diabete mellito: stato dell'arte, progetto Metabo come caso di studio

Il Diabete, modello paradigmatico delle malattie croniche, sta assumendo negli ultimi anni le proporzioni di una pandemia, che non ha intenzione di arrestarsi, ma del quale, con l’aumento dei fattori di rischio, aumentano prevalenza e incidenza. Secondo stime autorevoli il numero delle persone con diabete nel 2035 aumenterà fino a raggiungere i 382 milioni di casi. Una patologia complessa che richiede lo sforzo di una vasta gamma di professionisti, per ridurre in futuro in maniera significativa i costi legati a questa patologia e nel contempo mantenere e addirittura migliorare gli standard di cura. Una soluzione è rappresentata dall'impiego delle ICT, Information and Communication Technologies. La continua innovazione tecnologica dei medical device per diabetici lascia ben sperare, dietro la spinta di capitali sempre più ingenti che iniziano a muoversi in questo mercato del futuro. Sempre più device tecnologicamente avanzati, all’avanguardia e performanti, sono a disposizione del paziente diabetico, che può migliorare tutti processi della cura, contenendo le spese. Di fondamentale importanza sono le BAN reti di sensori e wearable device, i cui dati diventano parte di un sistema di gestione delle cure più ampio. A questo proposito METABO è un progetto ICT europeo dedicato allo studio ed al supporto di gestione metabolica del diabete. Si concentra sul miglioramento della gestione della malattia, fornendo a pazienti e medici una piattaforma software tecnologicamente avanzata semplice e intuitiva, per aiutarli a gestire tutte le informazioni relative al trattamento del diabete. Innovativo il Clinical Pathway, che a partire da un modello Standard con procedimenti semplici e l’utilizzo di feedback del paziente, viene progressivamente personalizzato con le progressive modificazioni dello stato patologico, psicologico e non solo. La possibilità di e-prescribing per farmaci e device, e-learning per educare il paziente, tenerlo sotto stretto monitoraggio anche alla guida della propria auto, la rendono uno strumento utile e accattivante.

Design and fluid dynamic analysis of a custom drip chamber in a medical disposable device

Negli ultimi anni, parallelamente allo sviluppo di calcolatori elettronici sempre più performanti, la fluidodinamica computazionale è diventata uno strumento di notevole utilità nell’analisi dei flussi e nello sviluppo di dispositivi medici. Quando impiegate nello studio di flussi di fluidi fisiologici, come il sangue, il vantaggio principale delle analisi CFD è che permettono di caratterizzare il comportamento fluidodinamico senza dover eseguire test in-vivo/in-vitro, consentendo quindi notevoli vantaggi in termini di tempo, denaro e rischio derivante da applicazioni mediche. Inoltre, simulazioni CFD offrono una precisa e dettagliata descrizione di ogni parametro di interesse permettendo, già in fase di progettazione, di prevedere quali modifiche al layout garantiranno maggiori vantaggi in termini di funzionalità. Il presente lavoro di tesi si è posto l’obiettivo di valutare, tramite simulazioni CFD, le performances fluidodinamiche del comparto sangue “camera venosa” di un dispositivo medico monouso Bellco impiegato nella realizzazione di trattamenti di emodialisi. Dopo una panoramica del contesto, è presentata una breve descrizione della disfunzione renale e dei trattamenti sostitutivi. Notevole impegno è stato in seguito rivolto allo studio della letteratura scientifica in modo da definire un modello reologico per il fluido non-Newtoniano preso in considerazione e determinarne i parametri caratteristici. Il terzo capitolo presenta lo stato dell’arte delle apparecchiature Bellco, rivolgendosi con particolare attenzione al componente “cassette” del dispositivo monouso. L’analisi fluidodinamica del compartimento “camera venosa” della cassette, che sarà presa in considerazione nei capitoli quinto e sesto, si inserisce nell’ambito della riprogettazione del dispositivo attualmente in commercio: il quarto capitolo si incentra sul suo nuovo design, ponendo specifico interesse sul layout della camera venosa di nuova generazione. Per lo studio dei flussi che si sviluppano internamente ad essa ci si è avvalsi del modulo CFD del software COMSOL multiphysics® (versione 5.0); la definizione del modello implementato e della tipologia di studio effettuato sono presi in considerazione nel quinto capitolo. Le problematiche di maggior impatto nella realizzazione di un trattamento di emodialisi sono l’emolisi e la coagulazione del sangue. Nell'evenienza che si verifichino massivamente occorre infatti interrompere il trattamento con notevoli disagi per il paziente, per questo devono essere evitate. Nel sesto capitolo i risultati ottenuti sono stati esaminati rivolgendo particolare attenzione alla verifica dell’assenza di fenomeni che possano portare alle problematiche suddette.

Ease of Application of Medical Compression-stocking Systems for the Treatment of Venous Ulcers

OBJECTIVE: To evaluate the ease of application of two-piece, graduated, compression systems for the treatment of venous ulcers. METHODS: Four kits used to provide limb compression in the management of venous ulcers were evaluated. These have been proven to be non-inferior to various types of bandages in clinical trials. The interface pressure exerted above the ankle by the under-stocking and the complete compression system and the force required to pull the over-stocking off were assessed in vitro. Ease of application of the four kits was evaluated in four sessions by five nurses who put stockings on their own legs in a blinded manner. They expressed their assessment of the stockings using a series of visual analogue scales (VASs). RESULTS: The Sigvaris Ulcer X((R)) kit provided a mean interface pressure of 46 mmHg and required a force in the range of 60-90 N to remove it. The Mediven((R)) ulcer kit exerted the same pressure but required force in the range of 150-190 N to remove it. Two kits (SurePress((R)) Comfort and VenoTrain((R)) Ulcertec) exerted a mean pressure of only 25 mmHg and needed a force in the range of 100-160 N to remove them. Nurses judged the Ulcer X and SurePress kits easiest to apply. Application of the VenoTrain kit was found slightly more difficult. The Mediven kit was judged to be difficult to use. CONCLUSIONS: Comparison of ease of application of compression-stocking kits in normal legs revealed marked differences between them. Only one system exerted a high pressure and was easy to apply. Direct comparison of these compression kits in leg-ulcer patients is required to assess whether our laboratory findings correlate with patient compliance and ulcer healing.

A Hybrid Multimodal Non-Rigid Registration of MR Images Based on Diffeomorphic Demons

n this paper we present a novel hybrid approach for multimodal medical image registration based on diffeomorphic demons. Diffeomorphic demons have proven to be a robust and efficient way for intensity-based image registration. A very recent extension even allows to use mutual information (MI) as a similarity measure to registration multimodal images. However, due to the intensity correspondence uncertainty existing in some anatomical parts, it is difficult for a purely intensity-based algorithm to solve the registration problem. Therefore, we propose to combine the resulting transformations from both intensity-based and landmark-based methods for multimodal non-rigid registration based on diffeomorphic demons. Several experiments on different types of MR images were conducted, for which we show that a better anatomical correspondence between the images can be obtained using the hybrid approach than using either intensity information or landmarks alone.

Referral practice among Swiss and non-Swiss walk-in patients in an urban surgical emergency department

To assess the relationship between nationality, gender and age and use of health services among patients visiting an urban university hospital emergency department (ED).

A systematic review of medical interventions for oral submucous fibrosis and future research opportunities

Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.

Personalized X-Ray Reconstruction of the Proximal Femur via Intensity-Based Non-rigid 2D-3D Registration

This paper presents a new approach for reconstructing a patient-specific shape model and internal relative intensity distribution of the proximal femur from a limited number (e.g., 2) of calibrated C-arm images or X-ray radiographs. Our approach uses independent shape and appearance models that are learned from a set of training data to encode the a priori information about the proximal femur. An intensity-based non-rigid 2D-3D registration algorithm is then proposed to deformably fit the learned models to the input images. The fitting is conducted iteratively by minimizing the dissimilarity between the input images and the associated digitally reconstructed radiographs of the learned models together with regularization terms encoding the strain energy of the forward deformation and the smoothness of the inverse deformation. Comprehensive experiments conducted on images of cadaveric femurs and on clinical datasets demonstrate the efficacy of the present approach.

Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI

Introduction Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery. Methods We investigated clinical outcomes of high-risk patients with severe aortic stenosis undergoing medical treatment (n = 71) or TAVI (n = 256) stratified by left ventricular ejection fraction (LVEF) in a prospective single center registry. Results Twenty-five patients (35%) among the medical cohort were found to have an LVEF≤30% (mean 26.7±4.1%) and 37 patients (14%) among the TAVI patients (mean 25.2±4.4%). Estimated peri-interventional risk as assessed by logistic EuroSCORE was significantly higher in patients with severely impaired LVEF as compared to patients with LVEF>30% (medical/TAVI 38.5±13.8%/40.6±16.4% versus medical/TAVI 22.5±10.8%/22.1±12.8%, p <0.001). In patients undergoing TAVI, there was no significant difference in the combined endpoint of death, myocardial infarction, major stroke, life-threatening bleeding, major access-site complications, valvular re-intervention, or renal failure at 30 days between the two groups (21.0% versus 27.0%, p = 0.40). After TAVI, patients with LVEF≤30% experienced a rapid improvement in LVEF (from 25±4% to 34±10% at discharge, p = 0.002) associated with improved NYHA functional class at 30 days (decrease ≥1 NYHA class in 95%). During long-term follow-up no difference in survival was observed in patients undergoing TAVI irrespective of baseline LVEF (p = 0.29), whereas there was a significantly higher mortality in medically treated patients with severely reduced LVEF (log rank p = 0.001). Conclusion TAVI in patients with severely reduced left ventricular function may be performed safely and is associated with rapid recovery of systolic left ventricular function and heart failure symptoms.