Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings

An Obscure Case of Hepatic Subcapsular Hematoma

Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma

A process evaluation of user fees abolition for pregnant women and children under five years in two districts in Niger (West Africa)

<p>Abstract</p> <p>Background</p> <p>African policy-makers are increasingly considering abolishing user fees as a solution to improve access to health care systems. There is little evidence on this subject in West Africa, and particularly in countries that have organized their healthcare system on the basis of the Bamako Initiative. This article presents a process evaluation of an NGO intervention to abolish user fees in Niger for children under five years and pregnant women.</p> <p>Methods</p> <p>The intervention was launched in 2006 in two health districts and 43 health centres. The intervention consisted of abolishing user fees and improving the quality of services (drugs, ambulance, etc.). We carried out a process evaluation in April 2007 using qualitative and quantitative data. Three data collection methods were used: i) individual in-depth interviews (n = 85) and focus groups (n = 8); ii) participant observation in 12 health centres; and iii) self-administered structured questionnaires (n = 51 health staff).</p> <p>Results</p> <p>The population favoured abolition; health officials and local decision-makers were in favour, but they worried about its sustainability. Among health workers, opposition to providing free services was more widespread. The strengths of the process were: a top-down phase of information and raising community awareness; appropriate incentive measures; a good drug supply system; and the organization of a medical evacuation system. The major weaknesses of the process were: the perverse effects of incentive bonuses; the lack of community-based management committees' involvement in the management; the creation of a system running in parallel with the BI system; the lack of action to support the service offer; and the poor coordination of the availability of free services at different levels of the health pyramid. Some unintended outcomes are also documented.</p> <p>Conclusion</p> <p>The linkages between systems in which some patients pay (Bamako Initiative) and some do not should be carefully considered and organized in accordance with the local reality. For the poorest patients to really benefit, it is essential that, at the same time, the quality of services be improved and mechanisms be put in place to prevent abuses. Much remains to be done to generate knowledge on the processes for abolishing fees in West Africa.</p