Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

Component resolved diagnosis in real life: the risk assessment of food allergy using microarray-based immunoassay.

BACKGROUND: The development of component-resolved diagnostics constitutes a potential breakthrough in food allergy testing, as detection of specific IgE (sIgE) to individual allergens may make it possible to establish the risk of a mild versus severe reaction. OBJECTIVE: To compare allergists' risk assessment based on the current decision making process with that of virtual allergen-oriented risk assessment through microarray-based immunoassay. METHODS: An observational, real-life study was performed on 86 adults with food allergy. The prescription of epinephrine was the surrogate marker of a severe reaction. In the same patients, the prescription of epinephrine based on the current decision making of the allergist and the independently established allergen-oriented risk assessment determined by microarray-based immunoassay were compared. RESULTS: Fair degree of agreement between the specialists' risk assessment and that of the microarray-based immunoassay (k index 0.372 (95% CI: 0.185- 0.559) p < 0.001) was documented. Three causes of discrepancy emerged: the poor sensitivity of the allergen microarray-immunoassay (51.9%), the differences in risk assessment established by the specialist and the microarray-immunoassay (33.3%), the non-inclusion of the causative allergen in the microarray-immunoassay platform (14.8%). CONCLUSION: Improvement of the diagnostic accuracy of microarray-immunoassay, combined with marrying its results to clinical information, could one day soon lead to changes in clinical practice in food allergy.

The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy.

BACKGROUND: The IgE response is directed against specific components from an allergenic source. The traditional diagnostic methods use whole extracts, containing allergenic, nonallergenic and cross-reactive molecules. This may pose diagnostic challenges in polysensitized patients. Microarray techniques detect specific IgE against multiple molecules, but their value in term of additional information and economic saving has not been yet defined. OBJECTIVE: We assessed the additional diagnostic information provided by an allergen microarray in a large population of polysensitized subjects. METHODS: In this multicentre study, allergists were required to carefully record diagnosis and treatment of consecutive patients referred for asthma/rhinitis, using the standard methodology (history, skin prick test, IgE assay). Then, a microarray allergen assay was carried out. Clinicians were required to review their diagnosis/treatment according to microarray results. RESULTS: 318 allergic patients (30% reporting also nonrespiratory symptoms) and 91 controls were enrolled. The clinicians reported at least one additional information from the microarray in about 60% of patients, this resulting in therapeutic adjustments. In 66% of patients IgE to pan-allergens were detectable, being this clinically relevant in 38% of patients with polysensitization to pollens. CONCLUSION: Microarray IgE assay represents an advancement in allergy diagnosis, as a third-level approach in polysensitized subjects, when the traditional diagnosis may be problematic.

Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

BACKGROUND: Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. OBJECTIVE: The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. METHODS: Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. RESULTS: The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. CONCLUSION: Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

Asthma severity and medical resource utilisation.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1-November 30, 1999, and 500 consecutive patients with asthma, aged 18-55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros (Euros) for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be Euros 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to Euros 720, Euros 1,046, Euros 1,535 and Euros 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.

Clinical value of quantitative long-term assessment of bcr-abl chimeric transcript in chronic myelogenous leukemia patients after allogeneic bone marrow transplantation.

BACKGROUND AND OBJECTIVE: For purposes of therapeutic decision making, we used quantitative polymerase chain reaction (PCR) for molecular follow-up of 55 patients with chronic myeloid leukemia (CML) in complete remission (CR) after allogeneic bone marrow transplantation (BMT) from HLA compatible donors. DESIGN AND METHODS: A total of 402 bone marrow samples from 40 patients transplanted in chronic phase (group 1) and 15 in accelerated/blastic phase (group 2) were analyzed by qualitative and quantitative PCR. RESULTS: Regarding clinical outcome, 34/40 (85%) group 1 vs. 8/15 (54%) group 2 patients are alive. Only 1/40 (2.5%) group 1 patient relapsed, as against 6/15 (40%) in group 2 (p = 0. 0002). At qualitative PCR, 8/40 (19%) group 1 vs. 9/15 (60%) group 2 patients were positive, with a significantly greater total number of positive samples in group 2 (33/129, 27% vs. 16/273, 5%; p<0.001). The probability of qualitative PCR positivity >1 year after BMT was significantly lower in group 1 patients (4/40 pts, 10% vs. 9/15 pts, 60%; p = 0.01). At quantitative PCR, 4/8 (50%) group 1 patients were positive only once (< 400 transcripts/microg RNA). In group 2, 9/15 (60%) patients had 3 or more positive samples (always with >4,000 copies/mg RNA); therapeutic interventions (cyclosporin A discontinuation, temporary a-interferon or donor lymphocyte infusion) restored molecular remission in 4/9 (44%) cases. INTERPRETATION AND CONCLUSIONS: This study indicates that quantitative PCR could provide practical indications capable of directing therapeutic interventions for transplanted CML patients, especially those transplanted in accelerated/blastic phase, for whom intensive monitoring is required.

Comparative study of terfenadine and cetirizine in hay fever: assessment of efficacy and central nervous system effects.

A daily dose of either terfenadine 120 mg or cetirizine 10 mg was compared in two parallel groups of patients suffering from hay fever. According to a double-blind, double-dummy, randomized design, 28 patients were treated with one of the two drugs once daily in the morning for 2 weeks during the 1990 grass pollen season. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching and itchy, watery, red eyes was evaluated by the investigator after a 1-week run-in period and at the end of the treatment. The patients made a daily record of the severity of symptoms on a diary card. In addition, drug-related central nervous system (CNS) effects were assessed at baseline and at the end of the treatment by neuropsychological tests aimed at investigating selective and sustained attention, visuomotor abilities and anxiety, and by quantitative, bit-mapped EEG. Both terfenadine and cetirizine produced a significant improvement in symptoms at endpoint without any significant difference between the two drugs. Drowsiness was referred by one patient in each treatment group. No significant impairment of psychomotor performance occurred with either drug. Quantitative EEG showed a significant power increase in the relative (%) delta band in both groups of treated patients. Although the difference was not statistically significant, a tendency towards greater involvement of the CNS was observed with the use of cetirizine. In conclusion, the results of this study confirm that terfenadine and cetirizine are equally effective in the management of hay fever. Some differentiated untoward EEG changes were also observed in relation to the drugs used, without any variation in neuropsychological performance.