Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program

Two randomized, double-blind, placebo-controlled studies demonstrated responses (≥50 000/μL) to fostamatinib in adults with long-standing immune thrombocytopenia (ITP). The long-term safety and efficacy of fostamatinib were evaluated in a follow-on, open-label extension (OLE) study. Patients received double-blind fostamatinib in the randomized trials, and responders continued the same dose, 100 to 150 mg BID, in the OLE study. Nonresponders received 100 mg BID for 4 weeks and could escalate to 150 mg BID at week 4. Endpoints included stable response, platelet count ≥50 000/μL at 4/6 biweekly (randomized trials) or 2/3 monthly visits (OLE), and overall response, ≥1 platelet count ≥50 000/μL during weeks 1 to 12. A total of 146 patients received fostamatinib including 123 in the OLE study. Median treatment duration was 6.7 months. Baseline median ITP duration was 8 years and median platelet count was 16 000/μL; prior treatments included thrombopoietic (TPO) agents (47%), splenectomy (35%), and rituximab (32%). Twenty-seven (18%) patients achieved a stable response with median duration of >28 months and a median platelet count of 89 000/μL. Sixty-four (44%) patients achieved an overall response (including stable responders) with a median platelet count of 63 000/μL and a median response duration of >28 months. Twenty-four of 71 (34%) patients who had failed TPO agents achieved overall responses to fostamatinib. The most common adverse events (AEs) were diarrhea, hypertension, nausea, epistaxis, and abnormal liver function tests. Most AEs were mild/moderate and resolved or were managed with dose reduction, dose interruption, and/or secondary medication. Almost half of the patients achieved an overall response, and most of these maintained their responses for >2 years. No new or increased frequency of AEs was seen at up to 31 months of treatment.     

Family Medicine in Egypt From Medical Students' Perspective: A Nationwide Survey

Phenomenon: Attitudes of medical students toward family medicine as a specialty choice can provide information on the future supply of family physicians. Due to the current worldwide shortage of family physicians, these attitudes, with their subsequent effects on the state and dynamics of the healthcare system, are important to investigate. Approach: A web-based questionnaire was sent to 600 medical students, selected by a systematic random sampling technique, in 7 Egyptian medical schools. Participants were surveyed to assess their perception of the family medicine specialty as a future career and explore the impact of different factors, including undergraduate family medicine clerkships, on their attitudes toward family medicine. Findings: We had a response rate of 75.2% (n = 451). Although 90.7% of students believed in the vital role that family medicine can play in Egypt's healthcare system, only 4.7% showed an intention to choose it as a future career. Students choosing family medicine as a first-career choice were more likely to have a prior contact with family physicians as consumers. Exposure to an undergraduate family medicine curriculum was associated with increased knowledge about family medicine but not the intentions to pursue it as a career. Insights: Medical students in Egypt have a positive perception of family medicine as an important specialty but low interest in its choice as a future career.     

Early postoperative MRI findings following surgery for herniated lumbar disc part II: A gadolinium-enhanced study

Summary The aim of our study was to evaluate the contrast-enhanced MR imaging (MRI) findings, in the early postoperative period, in unselected patients undergoing lumbar microdiscectomy (15/16 had total resolution of their symptoms). Contrast-enhanced imaging studies were performed, in all 16 patients of our series, before surgery, and at the third postoperative day and, two months after surgery. Postoperative paraspinal muscles enhancement was present in all patients. In the postoperative period, nerve root enhancement was present in 5/16 patients at the early survey and persisted in one after two months. A pseudohernia depicted as epidural intermediate signal intensity tissue, was seen in 13 patients at the third day MRI, and only in eight after two months. This pseudohernia enhanced peripherally in 8/13 patients and enhanced homogeneously in the remaining five at the first postsurgical examination; in the late MRI the peripheral enhancement was appreciable in only two patients while a homogeneous enhancement was observed in six.Clinical symptoms resolved completely in 14/16 patients on clinical evaluation at the third postoperative day, while the remaining two patients showed residual symptoms and signs of radicular compression. At the early MRI these two patients showed intradural nerve root enhancement. Two months later, one patient did not show the previously described nerve root enhancement and improved clinically, while the other had a positive Straight Leg Raising Sign with persistent intradural nerve root enhancement. In conclusion, no correlation between clinical course and contrastenhancement of pseudohernia and extradural nerve root was appreciable, although intradural nerve root enhancement seems to represent a clinically relevant finding.     

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.     

Serum vascular endothelial growth factor as a possible marker for early ectopic pregnancy

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) concentrations in women with normal intrauterine pregnancy (IUP), arrested IUP and ectopic pregnancy (EP). METHOD: This was a prospective, case-control study evaluating serum VEGF concentrations among 45 early pregnant women who subsequently were found to have an EP, a normal IUP or an arrested IUP (15 women in each group). Patients were stratified according to serum VEGF concentrations above and below 200 pg/ml. RESULTS: There was a significant difference in VEGF concentrations among women with EP, arrested IUP and normal IUP (306.1 +/- 26.5, 169.7 +/- 16.6 and 27.0 +/- 4.4 pg/ml respectively, P < 0.001). With a cut-off concentration of 200 pg/ml, serum VEGF could distinguish normal IUP from EP with a sensitivity of 88%, a specificity of 100% and a positive predictive value of 100%. Between EP and arrested IUP, the sensitivity was 87.5%, specificity 75% and positive predictive value of 77.8%. CONCLUSIONS: VEGF is a potential marker for EP. Its concentrations in women with EP are higher than in those with normal and arrested IUP.     

Prognostic impact of CD200 and CD56 expression in pediatric B-cell acute lymphoblastic leukemia patients

This study aimed to determine the prognostic impact of CD200 and CD56 expression in pediatric B cell acute lymphoblastic leukemia (B-ALL) patients, both of which have been implicated in immune tolerance and previously suggested as independent risk factors. CD200 has a central role in immune tolerance that protects stem cells and other critical tissues from immune damage. The expression of CD200/CD56 in leukemic blasts were assessed in leukemic blasts before chemotherapy in 43 bone marrow (BM) and/or peripheral blood (PB) samples by flow cytometry. Twenty eight of 43 B-ALL cases (65%) showed CD200 positive expression, 5 of 43 cases (11.6%) showed CD56 expression, and only 2 patients (4.7%) expressed both CD200 and CD56. Patients with CD200⁺ and CD56⁺ were significantly associated with lower platelet count; less tendency for induction of remission response as compared to negative ones (p = .01 for both). The overall survival (OS) and DFS were significantly shorter in CD200⁺ and CD56⁺ cases as compared to those with CD200^? and CD56^? expression. In conclusion, CD200 and/or CD56 positive expression in B-ALL at diagnosis suggest a poor prognosis and may be associated with biological aggressiveness.