Hematologic toxicity of sodium valproate

PURPOSE: Sodium valproate is a commonly used anticonvulsant in the management of childhood refractory epilepsy with good response rates and acceptable toxicity. Hepatotoxicity is the most widely recognized toxicity. With the use of higher drug levels to achieve adequate seizure control, hematologic toxicity is being increasingly encountered, and the pediatric hematologist is consulted for these problems in the pre- or perioperative setting. The purpose of this article is to characterize the various hematologic toxicities encountered in a clinical setting and to provide guidelines to assist in the management of these patients. METHODS: A literature review was undertaken to identify the hematologic toxicities of valproate used as monotherapy or polytherapy. Key words used in the search were valproate, hematology, and bleeding. RESULTS: Valproate can cause direct bone marrow suppression leading to aplastic anemia or peripheral cytopenia affecting one or more cell lines. Occasional fatal bone marrow failure, myelodysplasia, and a clinical picture resembling acute promyelocytic leukemia have also been seen. Thrombocytopenia, macrocytosis, neutropenia, and pure red cell aplasia can occur but are not reported to be life-threatening. A bleeding diathesis associated with valproate use may include thrombocytopenia, abnormal platelet function, and acquired von Willebrand disease type I. CONCLUSIONS: Hematologic toxicities of valproate are common, vary in onset and severity, are recurrent, transient, or persistent, and usually occur with a serum valproate level greater than 100 microg/mL. In most situations, even when highly clinically significant, they can be reversed with dosage reduction; drug discontinuation is rarely required. Potential adverse effects such as thrombocytopenia and leukopenia are easily detected by laboratory monitoring, which should be continued indefinitely at least on a quarterly basis. Caution for elective surgery is advised; preoperative coagulation studies should be done, including platelet function studies and von Willebrand factor levels. Perioperative use of DDAVP to increase von Willebrand factor levels and improve platelet function is appropriate in some cases.     

Day hospital rehabilitation a six-year study

Summary This paper describes the performance of a day hospital whose specific aims are the rehabilitation and work resettlement of disabled psychiatric patients. The results are reported and discussed in relation to other relevant studies.     

Tamoxifen use in patients with ductal carcinoma in situ and T1a/b N0 invasive carcinoma

BACKGROUND: The purpose of this study was to determine how often patients with ductal carcinoma in situ and T1a/b N0 cancer are offered and accept tamoxifen for secondary chemoprevention. STUDY DESIGN: A retrospective review of 284 patients with T1a/b N0 invasive cancer treated between February 1995 and December 2001 and 129 patients with DCIS treated after September 1998 was carried out. Patient and tumor characteristics associated with being offered and accepting tamoxifen were compared. RESULTS: Tamoxifen was offered to 67% of the invasive cancer patients and accepted by 76% (51% of the entire group). Hormone receptor status was the only significant predictor of being offered tamoxifen (p = 0.004). Older age (p = 0.04), Caucasian race (p = 0.01), and parity (p = 0.04) in premenopausal women were significant predictors of tamoxifen acceptance on univariate analysis. After the publication of the National Surgical Adjuvant Breast and Bowel Project P-1 trial, significantly more patients were offered tamoxifen (p = 0.02), but acceptance rates did not change. Tamoxifen was offered to 91% of the ductal carcinoma in situ patients and accepted by 73% (67% overall). Lumpectomy was associated with significantly higher rates of being offered (p = 0.02) and accepting tamoxifen (p = 0.002) on univariate analysis. CONCLUSIONS: Factors associated with tamoxifen risks and benefits correlate poorly with the use of the drug.     

Polymorphism of the interleukin-4, interleukin-13, and signal transducer and activator of transcription 6 genes in Indonesian children with minimal change nephrotic syndrome

BACKGROUND/AIMS: Minimal change nephrotic syndrome (MCNS) in children is frequently associated with allergy and immunoglobulin E (IgE) production. T-helper subtype 2 cytokines, such as interleukin (IL)-4 and IL-13, have been implicated in the regulation of IgE production. We investigated the associations of gene polymorphisms of IL-4, IL-13, and signal transducer and activator 6 (STAT6) in Indonesian children with MCNS (n = 84) and controls with neither allergic nor renal disease (n = 61). METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the IL-4 promoter gene polymorphism (-590C/T) and IL-13 gene polymorphism (4257G/A), and direct sequencing was used for the STAT6 3S untranslated region (2964G/A) polymorphism. RESULTS: There was a significant difference between the MCNS group and the controls in the genotypic distribution of IL-4 and IL-13 gene polymorphism. In the case of the IL-4 promoter gene, the frequency of the CC homozygote was significantly lower in the MCNS group than in the controls, while, in the case of IL-13, the frequency of the GG homozygote was significantly lower in the MCNS group. However, there was no difference between the MCNS group and the controls in the STAT6 gene polymorphism. CONCLUSION: The genetic variations in the IL-4 and IL-13 genes may be associated with predisposition to MCNS.     

Improving pilot response to in-flight strokes: a randomized controlled trial

BACKGROUND: When a passenger suffers an in-flight stroke (IFS), the pilot decides when to expedite access to ground care. Pilot pro-activeness towards IFS could improve outcome and should be promoted. Unfortunately, little is known about a pilot's stroke pro-activeness or limiting factors. METHODS: Randomized controlled trial of an educational intervention (American Stroke Association, 30-slide stroke awareness lecture) through an internet-based computer system using pilot students and instructors as subjects. Pilots completed pre-intervention and post-intervention tests of 25 simulated in-flight scenarios that describe strokes and other neurological and medical symptoms. Outcomes chosen were the percentage of pilots that would use a medical radio service, declare an emergency on board, or divert to the nearest airport for each scenario. RESULTS: Participant pilots (n = 104) were less likely to respond to IFS than to myocardial infarction (p < 0.001). Fear of retaliation by an employer was the most important modifiable limitation. The educational program increased the simulated rate of emergency declarations for in-flight vertebrobasilar strokes (p < 0.001) and subarachnoid hemorrhage (p < 0.001). CONCLUSIONS: Pilot-simulated response to certain IFS improves immediately after this educational intervention, which should be disseminated in schools and airlines. Further studies are needed to determine the long-term benefits of this intervention and the impact on actual diversion rates. Companies should also review their policies to shield pilots from retaliation when altering the flight plan for patients.