Intravenous sodium valproate in status epilepticus: review and Meta-analysis

Abstract

Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.

Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24?h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I² < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.

Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83–4.75), 24?h-efficacy: FE-OR = 1.32, 95% CI = (0.60–2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17–1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05–9.44), 24?h-efficacy: RE-OR = 0.88, 95% CI = (0.02–33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09–0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04–2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34–1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01–0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01–0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37–1.24)].

Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.     

Peptide Arrays for Development of PDGFRβ Affine Molecules

Purpose

Peptide arrays represent an attractive method for identification of amino acid motifs that bind to target structures. Spotting derivatives of the linear peptide platelet-derived growth factor receptor (PDGFR)-P1, which has been identified to bind the extracellular domain of the platelet-derived growth factor receptor beta, allows the synchronous investigation of the target affinity of numerous ligands.

Procedures

A peptide array randomizing PDGFR-P1 was constructed by replacement of each amino acid by all 20 natural amino acids. Incubation of the array with PDGFRβ and fibroblast growth factor receptor as negative control target was performed. Selected derivatives and fragments of PDGFR-P1 were chemically synthesized, radiolabeled, and evaluated in cell-based assays, using human pancreatic carcinoma BxPC3 and human breast cancer MCF7 cells.

Results

Binding capacity was increased for the derivate yG2 by exchange of ⁷S to ⁷R. Competition experiments demonstrated a binding decrease with increasing competitor concentration. Serum stability of yG2 was improved compared to the native ligand.

Conclusion

Peptide arrays were successfully applied for the improvement of the PDGFRβ binding peptide PDGFR-P1.     

Impact of clinical and procedural factors upon C reactive protein dynamics following transcatheter aortic valve implantation

AIM: To determine the effect of procedural and clinical factors upon C reactive protein(CRP) dynamics following transcatheter aortic valve implantation(TAVI).METHODS: Two hundred and eight consecutive patients that underwent transfemoral TAVI at two hospitals(Imperial, College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom and San Raffaele Scientific Institute, Milan, Italy) were included. Daily venous plasma CRP levels were measured for up to 7 d following the procedure(or up to discharge). Procedural factors and 30-d safety outcomes according tothe Valve Academic Research Consortium 2 definition were collected. RESULTS: Following TAVI, CRP significantly increased reaching a peak on day 3 of 87.6 ± 5.5 mg/d L, P 0.001. Patients who developed clinical signs and symptoms of sepsis had significantly increased levels of CRP(P 0.001). The presence of diabetes mellitus was associated with a significantly higher peak CRP level at day 3(78.4 ± 3.2 vs 92.2 ± 4.4, P 0.001). There was no difference in peak CRP release following balloonexpandable or self-expandable TAVI implantation(94.8 ± 9.1 vs 81.9 ± 6.9, P = 0.34) or if post-dilatation was required(86.9 ± 6.3 vs 96.6 ± 5.3, P = 0.42), however, when pre-TAVI balloon aortic valvuloplasty was performed this resulted in a significant increase in the peak CRP(110.1 ± 8.9 vs 51.6 ± 3.7, P 0.001). The development of a major vascular complication did result in a significantly increased maximal CRP release(153.7 ± 11.9 vs 83.3 ± 7.4, P = 0.02) and there was a trend toward a higher peak CRP following major/lifethreatening bleeding(113.2 ± 9.3 vs 82.7 ± 7.5, P = 0.12) although this did not reach statistical significance. CRP was not found to be a predictor of 30-d mortality on univariate analysis. CONCLUSION: Careful attention should be paid to baseline clinical characteristics and procedural factors when interpreting CRP following TAVI to determine their future management.     

E-cadherin expression in cervical epithelial cells of postmenopausal women: association with hormone therapy, tibolone, and raloxifene

This study assesses the possible associations between postmenopausal therapy (hormone therapy, raloxifene, and tibolone) and E-cadherin expression in normal cervical Papanicolaou smears (squamous, glandular, and metaplastic cells). E-cadherin immunostaining was less intense in metaplastic cells of women on tibolone, whereas hormone therapy and raloxifene were not associated with altered E-cadherin expression.     

Radiation dose,chemotherapy and risk of osteosarcoma after solid tumours during childhood

Osteosarcoma is the most frequent second primary cancer occurring during the first 20 years following treatment for a solid cancer in childhood. Using a cohort study of children treated for a solid cancer, we investigated the incidence and etiology of osteosarcoma as a second malignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiation and the risk of osteosarcoma, taking into account chemotherapy received. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-control study, we matched 32 cases and 160 controls for sex, type of first cancer, age at first cancer and the duration of follow-up. Parameters studied were the incidence of osteosarcoma, the cumulative local dose of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray = 1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field. Int. J. Cancer 77:370–377, 1998. © 1998 Wiley-Liss, Inc.     

Systematic irradiation of the vaginal vault in stage I endometrial carcinoma

One hundred and twenty patients with clinical pathological stage I carcinoma of the endometrium were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and either pre- or postoperative intracavitary cesium insertion. External pelvic irradiation (45-50 Gy in 5 weeks) was given postoperatively in 36 cases, mainly for deep myometrial invasion. All the women have been followed for a minimum of 5 years. The overall 5-year survival rate is 86%. According to histological grading, the 5-year survival was 88, 83 and 57% for grades 1 (90 patients), 2 (23 patients) and 3 (7 patients) respectively. A total of 17 local and distant failures were observed: 10 patients had distant metastases, six patients had a pelvic failure and one had both. There was only one isolated vaginal recurrence. Depth of myometrial invasion was not a statistically significant indicator of outcome. Survival rates were comparable in pre- and postoperatively treated patients.