[Assessment of the budgetary impact of an emicizumab therapy introduction for patients with severe haemophilia A without inhibitor]. / Évaluation de l'impact budgétaire de l'introduction d'un traitement par émicizumab chez des patients atteints d'hémophilie A sévère congénitale sans inhibiteur.

Since March 2019, émicizumab is indicated for the treatment of patients with severe haemophilia A without inhibitor. This therapy's price amounts approximately to €33 600 per 4 weeks for a 70kg patient which represents about two times more than a factor VIII concentrates treatment's price. This study aims to assess the budgetary impact for the French Health Insurance of an émicizumab therapy introduction for patients with severe haemophilia A without inhibitor. It was an observational, retrospective, and monocentric study. Every severe haemophilia A without inhibitor patient over 18 years old followed at the Cochin Hospital haemophilia treatment centre who received émicizumab from June 2020 and for at least one year have been included. The budgetary impact was estimated by comparing the total costs of patient care the year before versus the year after émicizumab initiation. Total costs of patient care included prices of i) treatments consumed, ii) consultations with specialist physicians, iii) hospitalizations and iv) imaging procedures. Thirty-eight patients were included. The total cost of patient care increased significantly the year after émicizumab introduction (P < 0.0001). On average, this cost was estimated at €537 887 ± €137 139 per patient whereas it was at €151 442 ± €94 708 the year before. While costs of physician consultations increased, no significant difference has been reported about hospitalizations and imaging costs. Over a one-year period, émicizumab therapy significantly increased the total costs of patient care. It is mostly caused by the drug price itself.

[Assessment of the impact of pharmaceutical consultations at initiation of a treatment with emicizumab in patients with severe hemophilia A without inhibitors]. / Évaluation de l'impact de consultations pharmaceutiques à l'instauration d'un traitement par émicizumab chez les patients hémophiles A sévères sans inhibiteurs.

Since 2019, severe haemophilia A without inhibitors can be treated with emicizumab. Its action, route of administration and management justified the creation of new tools for therapeutic education sessions addressed to patients. The main objective of our work was to assess the knowledge and skills acquired by patients after therapeutic education. The various documents created were a video, a slideshow, clinical cases in form of cards, and summary sheets intended for patients. At treatment beginning, a pharmaceutical consultation was proposed to all patients. Two months later, an evaluation was carried out and a second pharmaceutical consultation aimed to consolidate the achievements of patients. Simultaneously, a clinical self-evaluation by the patients was carried out. Thirty-six patients were included in the study. Theoretical items: method of manufacture, mechanism of action and regimen, are known for more than ¾ of patients. Practical skills, such as administration modalities, management of missed doses or bleeding, are familiar for more than 8 out of 10 patients. Sixteen (44.4%) patients presented an up-to-date haemophilia card. The assessment of the knowledge and skills of patients is encouraging since most of the items are acquired. These result highlights the interest of the new tools developed for the therapeutic education sessions.

Halotolerant and metalotolerant bacteria strains with heavy metals biorestoration possibilities isolated from Uburu Salt Lake, Southeastern, Nigeria.

Environmental contaminations by heavy metals are currently an increasing public health concern globally. One key challenge of these toxic metals is the extremely difficulties involved in their detoxification from the environment and effluents because of their non-degradability. An efficient biologic agent with potentials of remediating these toxic metals may ease these ever-increasing problems. We reported toxic metals tolerance and bioremediation potentials of novel bacteria sp. Strains USL2S, USL4W and USL5W isolated from Uburu salt lake, Ebonyi State, Nigeria. The phenotypic characteristics and the 16S rRNA gene analyses revealed that USL2S strain belongs to the genus Klebsiella, whereas USL4W and USL5W strains belong to the genus Pseudomonas. The bacteria isolates grew well in media containing 5-15 % of sodium chloride. The bacteria isolate showed capacity to tolerate 50.0 mM Hg+2 and Pb+2, 17.0, 12.50 and 4.0mM Ni+2, Cd+2, and Zn+2 respectively in solid media. Pseudomonas putida A4W Strain also tolerated 16.0 mM Cu+2, while Klebsiella sp. Strain USL2S, Pseudomonas putida USL5W Strain tolerated 4.0 mM each. AAS analyses showed 85, 95, and 95 % Hg; 97.13, 98.89, and 97.55 % Pb; 73.33, 77.42 and 69.72 Cd; 88.06, 99.54, and 97.91 % Ni; 100, 100 and 83.62% Cu; 42.30, 84.52 and 98.80 % Zn removal from media broth incorporated with the tested metals by Klebsiella sp. USL2S, Pseudomonas sp. Strain USL5W and Pseudomonas sp. USL4W respectively. We therefore recommend these novel moderately halophilic and metal tolerant isolates as possible biologic agents for effective bioremediation of mercury, lead, cadmium, nickel, copper and zinc in contaminated environments and effluents.

Surgical treatment of glottic cancer: retrospective analysis of 192 cases in a multidisciplinary tertiary care centre in Pune, India.

OBJECTIVES: A multidisciplinary team approach is required for the preservation of voice and appropriate management of glottic cancer. This study aimed to investigate the outcomes of surgically treated glottic cancers of all stages. All aspects of surgical management, such as laser cordectomy, partial laryngectomy, total laryngectomy with voice prosthesis, and salvage laryngectomy, conducted at a single tertiary care institute in India, were reviewed. METHOD: A retrospective analysis of hospital records was performed for 192 glottic cancer patients who were surgically treated between 2003 and 2007. RESULTS: Patients with tumour stages 1 or 2 glottic cancer treated with laser cordectomy had a local control rate of 85 per cent and five-year survival rate of 98.6 per cent. The findings suggest that the number of partial laryngectomies performed for stage 3 tumours is declining. Patients with a tumour stage 3 lesion with a fixed hemilarynx or a tumour stage 4 lesion, treated with total laryngectomy, were found to have a five-year survival rate of 61.6 per cent. Nodal status was significantly associated with five-year survival rate. CONCLUSION: Surgery offers a viable five-year survival rate in glottic cancer patients.

Intracranial low-grade chondrosarcoma with hyperostosis of the skull: a case report.

We describe a case of intracranial chondrosarcoma in a 46-year-old woman. The preoperative diagnosis was meningioma as plain radiography and computed tomography of the head revealed a tumor with discrete calcifications predominantly in the right frontoparietal region and hyperostosis of the inner table of the skull overlying the tumor. However, the tumor was histologically composed of cartilaginous tissue without meningiomatous differentiation and the final diagnosis was a low-grade chondrosarcoma based on its histological appearance and size, together with the radiologic images. Intracranial chondrosarcoma occurring above the skull base is extremely rare and 19 cases were found in our literature review. Intracranial chondrosarcoma showing hyperostosis of the skull has not been reported in the cases. The discussion includes its differential diagnosis, origin, and clinical behavior.

Structural characteristic of splenic sinuses in idiopathic portal hypertension.

Splenic sinuses in idiopathic portal hypertension (IPH; 8 patients), liver cirrhosis (LC; 14 patients) and in regenerating autotransplanted spleens from 25 rats were compared with each other by scanning electron microscopy (SEM) and immunohistochemistry using antibodies against proliferating cell nuclear antigen (PCNA). Spleens obtained from six patients with gastric carcinoma and from five untreated adult rats were examined as controls. SEM of the sinuses showed that in IPH endothelial cells became irregular in shape, and the interendothelial slits of sinuses were irregularly enlarged. Sinus endothelial processes traversing the sinusal lumen were also found. The same changes were observed in the proliferating sinuses during regeneration of splenic tissue after autotransplantation in rats, but disappeared when the regeneration was completed. Irregular endothelial cells were few in LC. PCNA-positive sinus endothelial cells were increased in number in IPH as compared with those in LC; the mean number of PCNA-positive ones per cm2 was 45.4 in IPH and 8.2 in LC. It was suggested that, from SEM observation of sinus endothelial cells and counting PCNA-positive sinus endothelial cells, the sinuses of the spleen in IPH consist of proliferating endothelial cells or are in the state of increased proliferation. In conclusion, splenomegaly in IPH was presumed to be caused by proliferation of sinus endothelial cells, and by the increased splenic blood flow in the irregularly widened interendothelial slits of the sinuses.

Simple method for quantifying disorientation of myofiber in endomyocardial biopsy specimens using an image analyzer.

The disarray of cardiac myofibers was morphometrically evaluated in biopsy specimens, obtained from patients with hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD), chronic phase myocarditis and controls. Microphotographs of myocardium were taken at a final magnification of x 250. For each segment of myofibers, the longitudinal direction was traced on a transparent sheet, and the angle of the traced direction to the baseline was measured by an image analyzer. The standard deviation of the angles was used as an indicator of myofiber disarray. The histograms showed a narrow variation in the control group, but a wide variation in the patients with HCM, HHD and chronic phase myocarditis. The mean value of standard deviations of myofiber angles in HCM was significantly larger than that in the other groups. In HCM, the standard deviation of the myofiber angle proved to correlate positively with IVST/LVPWT (the thickness ratio of interventricular septum to the left ventricular posterior wall) (r = 0.70, p < 0.05), and also with LVEDP (left ventricular end-diastolic pressure) (r = 0.66, p < 0.05). In conclusion, the image analyzer serves as a simple and useful tool in quantifying the disorientation of myofibers and estimating the correlation between the histological and clinical findings.