Timing of elective pre-labour caesarean section : A decision analysis

BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548), and reports consultancy for ObsEva, Merck and Guerbet.Peer reviewedPublisher PD

Dose-Dependent Thresholds of 10-ns Electric Pulse Induced Plasma Membrane Disruption and Cytotoxicity in Multiple Cell Lines

In this study, we determined the LD50 (50% lethal dose) for cell death, and the ED50 (50% of cell population staining positive) for propidium (Pr) iodide uptake, and phosphatidylserine (PS) externalization for several commonly studied cell lines (HeLa, Jurkat, U937, CHO-K1, and GH3) exposed to 10-ns electric pulses (EP). We found that the LD50 varied substantially across the cell lines studied, increasing from 51 J/g for Jurkat to 1861 J/g for HeLa. PS externalized at doses equal or lower than that required for death in all cell lines ranging from 51 J/g in Jurkat, to 199 J/g in CHO-K1. Pr uptake occurred at doses lower than required for death in three of the cell lines: 656 J/g for CHO-K1, 634 J/g for HeLa, and 142 J/g for GH3. Both Jurkat and U937 had a LD50 lower than the ED50 for Pr uptake at 780 J/g and 1274 J/g, respectively. The mechanism responsible for these differences was explored by evaluating cell size, calcium concentration in the exposure medium, and effect of trypsin treatment prior to exposure. None of the studied parameters correlated with the observed results suggesting that cellular susceptibility to injury and death by 10-ns EP was largely determined by cell physiology. In contrast to previous studies, our findings suggest that permeabilization of internal membranes may not necessarily be responsible for cell death by 10-ns EP. Additionally, a mixture of Jurkat and HeLa cells was exposed to 10-ns EP at a dose of 280 J/g. Death was observed only in Jurkat cells suggesting that 10-ns EP may selectively kill cells within a heterogeneous tissue

A Dual-Beam Irradiation Facility for a Novel Hybrid Cancer Therapy

In this paper we present the main ideas and discuss both the feasibility and the conceptual design of a novel hybrid technique and equipment for an experimental cancer therapy based on the simultaneous and/or sequential application of two beams, namely a beam of neutrons and a CW (continuous wave) or intermittent sub-terahertz wave beam produced by a gyrotron for treatment of cancerous tumors. The main simulation tools for the development of the computer aided design (CAD) of the prospective experimental facility for clinical trials and study of such new medical technology are briefly reviewed. Some tasks for a further continuation of this feasibility analysis are formulated as well.Comment: 18 pages, 3 tables, 8 figures, 50 reference

Cost-effectiveness of CTA, MRA and DSA in patients with non-traumatic subarachnoid haemorrhage

OBJECTIVES: Intra-arterial digital subtraction angiography (DSA), magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) are imaging modalities used for diagnostic work-up of non-traumatic subarachnoid haemorrhage. The aim of our study was to compare the cost-effectiveness of MRA, DSA and CTA in the first year after the bleed. METHODS: A decision model was used to calculate costs and benefits (in quality-adjusted life-years [QALYs]) that accrued to cohorts of 1,000 patients. Costs and characteristics of diagnostic tests, therapy, patients’ quality of life and associated costs were respected. The diagnostic strategy with highest QALYs and lowest costs was considered most cost-effective. RESULTS: DSA was the most effective diagnostic option, yielding on average 0.6039 QALYs (95 % CI, 0.5761–0.6327) per patient, followed by CTA 0.5983 QALYs (95 % CI, 0.5704–0.6278) and MRA 0.5947 QALYs (95 % CI, 0.5674–0.6237). Cost was lowest for DSA (39,808 €; 95 % CI, 37,182–42,663), followed by CTA (40,748 €; 95 % CI, 37,937–43,831) and MRA (41,814 €; 95 % CI, 38,730–45,146). A strategy of CTA followed by DSA if CTA was negative or coiling deemed not feasible, was as effective as DSA alone at average costs of 39,767€ (95 % CI, 36,903–42,402). CONCLUSION: A combined strategy of CTA and DSA was found to be the most cost-effective diagnostic approach. MAIN MESSAGES: • We defined a standard model for cost-effectiveness analysis in diagnostic imaging. • Comparing total 1-year health costs and benefits, CTA is superior to MRA. • A strategy of combining CTA and DSA was found to be the most cost-effective diagnostic approach

A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations

Recent studies of cerebral pathology in patients with schizophrenia have focused on symptomatological and electrophysiological correlates of reduced temporal lobe structure volumes. Volume deficits of the left superior temporal gyrus have been correlated with auditory hallucinations as well as to left-sided P300 amplitude reduction. However, caution is needed to interpret correlational data as evidence of a specific relationship. Therefore, a controlled study was undertaken on schizophrenic patients with and without auditory hallucinations. MRI-defined volumes of the left superior temporal gyrus and other temporal lobe structures were quantified from 3-mm coronal slices in 15 schizophrenic patients with chronic auditory hallucinations (hallucinators), 15 schizophrenic patients without auditory hallucinations (nonhallucinators) and 17 healthy controls. In all subjects a simple oddball paradigm was used to elicit P300 responses at temporal and centro-parietal electrode sites. No evidence was found for volume reductions of temporal lobe structures in the combined patient group compared with controls, or in the hallucinators compared with the nonhallucinators. The patients did show left P300 amplitude reduction compared with controls, particularly in the hallucinator group. Correlations between volumes of left temporal lobe structures and left P300 amplitudes were low and not significant. The results of the present study do not indicate that auditory hallucinations and associated abnormal electrophysiological activity are the consequence of atrophy of localized temporal lobe structures. However, replication in a larger sample of subjects is needed before firm conclusions can be drawn

Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs)

Treatment and Survival of Elderly Patients with Stage I–II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium

Background: Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. Objective: The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I–II pancreatic cancer in the EURECCA Pancreas Consortium. Methods: This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. Results: In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. Conclusions: Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I–II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment