Cost-effectiveness of benralizumab versus mepolizumab and dupilumab in patients with severe uncontrolled eosinophilic asthma in Spain.

OBJECTIVE: To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. METHODS: Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), -0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. RESULTS: Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. CONCLUSIONS: Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.

Roles of age, length of service and job in work-related injury: a prospective study of 446 120 person-years in railway workers.

OBJECTIVES: Because work-related injuries are common and yet the mechanisms through which various types of injuries relate to age, length of service and job remain unknown, this study assessed the role of age, length of service and job in work-related injury. METHODS: Prospective study of all 164,814 permanently employed male workers at the French national railway company during 1998-2000, based on the company's injury database: 446,120 person-years, 15,195 injuries with working days lost, coded using the company's injury classification, which is derived from that of the French health insurance scheme. We investigated the incidence of 10 types of injury: fall on same level, fall to lower level, handling materials/machine parts during assembly, handling objects, lifting/handling equipment, collision with/by moving objects, collision with/by vehicles, operating machines/equipment, using hand tools and other injuries. Data were analysed using negative binomial regression. RESULTS: Workers aged <25 years were subject to a higher injury risk from handling materials/machine parts during assembly, and collision with/by moving objects or vehicles. Older workers, especially those aged 50-55 years, were subject to a higher risk of fall and injury resulting from lifting/handling materials/equipment/objects or from collision with/by moving objects/vehicles. Using hand tools was a risky task for workers aged <30 or > or =40 years. The relative risk decreased steadily with increasing length of service with the company, from 2.6 for 1 year to 1.0 for > or =30 years, and the slope of the trend is stronger for fall to lower level, lifting/handling materials/equipment and collision with/by moving objects. CONCLUSION: Younger and older ages and shorter length of service are at risk for various types of injuries. Preventive measures should improve working conditions, especially for younger/older ages, provide knowledge through specific training during the first years in a job and help workers to be more aware of risks associated with their age, years of employment and job.

ADAM33 gene polymorphisms in chronic obstructive pulmonary disease.

STUDY OBJECTIVE: The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants. Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving. In the present study, we investigated whether single nucleotide polymorphisms in "a disintegrin and metalloprotease" 33 (ADAM33) are associated with the development and course of COPD. PATIENTS AND DESIGN: We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively. To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease. RESULTS: In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively). The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47). CONCLUSION: The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD. Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course.

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes.

Naturally scrapie-affected ewes present a syndrome of hypercortisolism as evaluated by measuring total plasma cortisol concentrations. The objective of this study was to investigate the plasma protein binding of cortisol and to evaluate the concentration of the biologically active free fraction of cortisol in scrapie-affected ewes. Corticosteroid binding globulin (CBG) binding parameters were evaluated by equilibrium dialysis in 13 naturally scrapie-affected ewes and nine healthy ewes, during two periods of the clinical evolution of the disease. The hypercortisolism of the scrapie-affected ewes was confirmed by a significant increase of the plasma 20 beta-dihydrocortisol and cortisone concentrations, while total cortisol concentrations, obtained from an isolated sample, did not differ between scrapie-affected and control ewes. The scrapie diagnosis was confirmed by histopathology. The CBG maximal capacity (B(max)) was two times lower in scrapie-affected ewes than in healthy ewes (37+/-32 nM and 73+/-28 nM respectively). The dissociation constant K(d) (8.8+/-3.7 nM and 9.8+/-3.0 nM respectively) and the non-specific constant value of binding to albumin (1.13+/-0.18 and 1.14+/-0.23 respectively) did not differ significantly between diseased and control ewes. The significant increased concentrations of CBG-free cortisol (i.e. both albumin-bound and free cortisol fractions) in scrapie-affected ewes indicates that total plasma cortisol concentration is not an appropriate index of pituitary-adrenocortical hyperactivity. In conclusion, ewes with naturally occurring scrapie display a syndrome of hypercortisolism associated with a lower CBG binding capacity which leads to an overexposure of glucocorticoid-sensitive targets to CBG-free cortisol. The physiopathological consequences of this overexposure on the development of the neurodegenerative process in prion disease are discussed.

Determinants of accident proneness: a case-control study in railway workers.

BACKGROUND: Accident proneness or workers who have more frequent occupational injuries is common but the role of occupational and individual factors has rarely been studied. AIM: To assess the relationships of certain occupational and individual characteristics with frequency of occupational injuries. METHOD: This case-control study included 1305 male workers with occupational injuries during 1999-2000 and 1305 controls from a railway company. A standardized questionnaire was completed by the occupational physician in the presence of the subject. The data were analysed using logistic regression. RESULTS: Having more than one injury was associated with short service in the present job, younger age, sleep disorders, smoking, requesting a job change, physical disability and lack of physical activity. Safety training was negatively related to injury frequency. Short service in the present job was the only significant factor for single injuries. CONCLUSION: This study identified a number of work and individual factors that predicted occupational injury frequency and may be useful in designing preventative measures. Occupational physicians could assist workers to be more aware of the risks and to find remedial measures.

Adverse haematological effects of vinblastine, prednisolone and cimetidine treatment: a retrospective study in fourteen dogs with mast cell tumours.

Vinblastine toxicity is poorly documented in dogs. The aim of this study was to investigate the haematological alterations in dogs treated with vinblastine and prednisolone. Fourteen dogs with mast cell tumours (MCT) were selected on at least one of the following criteria: lymph node infiltration, surgical margin infiltration, grade II MCTs with Ki-67 >10%, and grade III MCTs. Starting 15 days after surgery, the dogs were given vinblastine (2 mg/m2 i.v. four times weekly, then twice monthly for 2 months) and prednisolone (2 mg/kg/day p.o.). An EDTA blood sample was collected weekly for complete blood count (CBC). A total of 98 doses of vinblastine were given to the 14 dogs and 114 CBC were performed. Abnormal haematological findings were observed in 12 CBCs from five dogs, which represent a prevalence of 20% of the total CBCs performed in these animals. The most prevalent abnormal finding was thrombopenia (9/12) most often with grade I toxicity (6/9). In conclusion, the risk of occurrence of adverse haematological effects resulting from vinblastine-prednisolone treatment seems limited in dogs with MCT and it should not be overestimated.

[Study on the relationship between serum alpha 1 antitrypsin level, the phenotype Pi and various bronchopulmonary diseases]. / Recherche de liaisons entre le taux sérique d'alpha-1-antitrypsine, le phénotype P1 et différentes affections broncho-pulmonaires

The authors determined in 418 adults, males and females, admitted to hospital on the Respiratory Unit of the Montpellier University Hospital, the serum levels of alpha-1-antitrypsin, phenotype Pi and serum immunoglobulin levels. They compare these data together and with the diagnosis using a mathematical method known as factorial correspondence analysis.

Individual characteristics in occupational accidents due to imbalance: a case-control study of the employees of a railway company.

BACKGROUND: Falls are frequent occupational accidents, and are responsible for a significant amount of lost working time and, more importantly, for a high mortality. The factors involved in falling mechanisms can be of external or individual origin, the latter being less well identified. AIMS: To assess the relations between certain individual characteristics and occupational accidents due to imbalance. METHODS: A total of 427 male employees, who had been victims of at least one occupational accident with sick leave due to imbalance (cases) and 427 controls were recruited among the employees of a large French railway company. A standardised questionnaire on life conditions and professional factors, and a description of the accidents was filled in by an occupational physician for each subject. RESULTS: Some job categories were more affected by a specific release mechanism of work related falls. Certain individual characteristics such as smoking, alcohol consumption, inactivity, sleep disorders, and request for a job change were correlated with the occurrence of occupational accidents. Sick leaves of eight days or over were more frequent in older and overweight injured workers. Some lesions were linked with the specific fall released mechanisms. CONCLUSIONS: Individual characteristics can increase the risk of occupational accidents, especially falling. This study identified subjects most at risk on whom prevention related to working conditions and falls could be focused.

Benzene exposure in car mechanics and road tanker drivers.

The purpose of this study was to identify professional factors related to benzene exposure and to deduce suitable safety measures. Atmospheric benzene, urinary muconic acid (tt-MA) and leukocyte alkaline phosphatase activity (LAPA) were evaluated among 66 car mechanics, 34 road tanker drivers, and 28 nonexposed workers. Professional and medical questionnaires were filled in at the same time. Atmospheric benzene was significantly higher among road tanker drivers than among car mechanics. The arithmetic mean +/- SD, median, and geometric mean values were, respectively, 0.48 +/- 1.49, 0.14, and 0.06 mg/m3 among car mechanics and 1.88 +/- 4.18, 0.68, and 0.65 mg/m3 among road tanker drivers. In the latter case the increase was caused by transport of unleaded petrol and correlated with the volume of the tank. Among car mechanics, tobacco smoking, windy conditions, dismantling of petrol filters, and handling of petrol increased atmospheric benzene levels. Urinary muconic acid was increased significantly among car mechanics (148 +/- 137, 127, and 111 micrograms/g) and among road tanker drivers (309 +/- 420, 137, and 151 micrograms/g) as compared with the controls (49 +/- 46, 33, and 33 micrograms/g). Among road tanker drivers, alcohol intake and transportation of unleaded petrol increased the excretion of muconic acid, which was also directly related to the volume of the tank. Among car mechanics, professional factors (dismantling of petrol filters, handling of and washing of hands with petrol) and nonprofessional factors (tobacco smoking and damaged skin on the hands and forearms) increased muconic acid excretion. In the control group, tobacco smoking increased its excretion. LAPA was not significantly modified among exposed workers. There was a weak but significant linear correlation between LAPA and muconic acid. These results suggest that to reduce exposure to benzene in unleaded petrol, individual and collective safety measures should be imposed in both occupations.