Bispectral index is a topographically dependent variable in patients receiving propofol anaesthesia

Background. As very strong agreement has been reported between bispectral index (BIS) values measured from the occipital and frontal skull areas, we compared BIS values measured from central and parietal areas with those from frontal area to investigate whether BIS is really a topographically dependent or topographically independent variable. Methods. Twenty patients, ASA I-II, non-obese, aged 18-62 yr and with no neurological disorders were enrolled. Based on the 10-20 international landmarks, five silver dome electrodes were positioned: F7, C3, P7, Cz (common reference) and Fp1 (ground). Using frontal (F7-Cz), central (C3-Cz) and parietal (P7-Cz) electrode montages, the corresponding BIS values were simultaneously recorded with an Aspect A-1000 monitor (software v3.12). The BIS values were recorded at the propofol concentration allowing laryngeal mask insertion, which was maintained during the 10 min data collection period in absence of additional external stimuli. Data were analysed using the Kruskall-Wallis, Wilcoxon paired sign with Bonferroni correction, Bland-Altman and linear correlation tests. Results. At the predicted effect target propofol concentration 4-8 μg ml−1, the 10 min mean BIS (median [min-max]) were 32 [20-44], 46 [28-68] and 58 [41-72] for the frontal, central and parietal leads, respectively. Differences between these BIS recordings were statistically significant (P<0.0001, Kruskall-Wallis; P<0.005, Wilcoxon paired sign test). Conclusions. The present results provide evidence that BIS index is a topographically dependent variable in patients receiving propofol anaesthesi

The case for Option B and Optional B+: Ensuring that South Africa’s commitment to eliminating mother-to-child transmission of HIV becomes a reality

In a previous issue of the Southern African Journal of HIV Medicine, Pillay and Black summarised the trade-offs of the safety of efavirenz use in pregnancy (Pillay P, Black V. Safety, strength and simplicity of efavirenz in pregnancy. Southern African Journal of HIV Medicine 2012;13(1):28-33.). Highlighting the benefits of the World Health Organization’s proposed options for the prevention of mother-to-child transmission (PMTCT) of HIV, the authors argued that the South African government should adopt Option B as national PMTCT policy and pilot projects implementing Option B+ as a means of assessing the individual- and population-level effect of the intervention. We echo this call and further propose that the option to remain on lifelong antiretroviral therapy, effectively adopting PMTCT Option B+, be offered to pregnant women following the cessation of breastfeeding, for their own health, following the provision of counselling on associated benefits and risks. Here we highlight the benefits of Options B and B+

Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.

BackgroundCabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts.Patients and methodsEligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily. After an initial 12-week cabozantinib treatment period, patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead-in stage was objective response rate (ORR) at week 12, and the primary endpoint of the randomized stage was progression-free survival (PFS).ResultsAmong the 41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a confirmed partial response (PR). The week 12 disease control rate (PR or SD) was 66% (Asian subgroup: 73%). Of patients with ≥1 post-baseline scan, 78% had tumor regression, with no apparent relationship to prior sorafenib therapy. Alpha-fetoprotein (AFP) response (&gt;50% reduction from baseline) occurred in 9 of the 26 (35%) patients with elevated baseline AFP and ≥1 post-baseline measurement. Twenty-two patients with SD at week 12 were randomized. Median PFS after randomization was 2.5 months with cabozantinib and 1.4 months with placebo, although this difference was not statistically significant. Median PFS and overall survival from Day 1 in all patients were 5.2 and 11.5 months, respectively. The most common grade 3/4 adverse events, regardless of attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia (15%). Dose reductions were utilized in 59% of patients.ConclusionsCabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.Trial registration numberNCT00940225

safety and efficacy of trifluridine tipiracil ftd tpi in metastatic colorectal cancer mcrc patients according to previous treatment with regorafenib in the international phase iiib preconnect study

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A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

Oral capecitabine (Xeloda&lt;sup&gt;&#174;&lt;/sup&gt;) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by &gt;75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

canstem303c trial a phase 3 study of napabucasin napa in combination with 5 fluorouracil 5 fu leucovorin and irinotecan folfiri in adult patients pts with previously treated metastatic colorectal cancer mcrc trial in progress

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o 013safety and efficacy of trifluridine tipiracil in previously treated metastatic colorectal cancer mcrc preliminary results from the phase iiib international open label early access preconnect study

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A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

Background:Approximately 5%-10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome versus paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by fluorescence in situ hybridization. Patients and methods:Patients were randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2 administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point was progression-free survival (PFS). Safety outcomes were assessed and an exploratory biomarker analysis was undertaken. Results:Of 71 patients randomized (AZD4547 n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547 n = 40, paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse events was similar in both treatment arms. Exploratory biomarker analyses revealed marked intratumor heterogeneity of FGFR2 amplification and poor concordance between amplification/polysomy and FGFR2 mRNA expression. Conclusions:AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated