Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial.

Background: Abiraterone acetate plus prednisone and enzalutamide are both used for the treatment of metastatic castration-resistant prostate cancer. We aimed to determine the best sequence in which to use both drugs, as well as their second-line efficacy.

Methods: In this multicentre, randomised, open-label, phase 2, crossover trial done in six cancer centres in British Columbia, Canada, we recruited patients aged 18 years or older with newly-diagnosed metastatic castration-resistant prostate cancer without neuroendocrine differentiation and Eastern Cooperative Oncology Group performance status 2 or less.

Canadian Cancer Trials Group (CCTG) IND211: A randomized trial of pelareorep (Reolysin) in patients with previously treated advanced or metastatic non-small cell lung cancer receiving standard salvage therapy.

Objectives: Pelareorep (reolysin), a Dearing strain of reovirus serotype 3, has demonstrated oncolytic activity as single agent and synergy with chemotherapy. We evaluated pelareorep, combined with standard second-line chemotherapy in patients with non-small cell lung cancer (NSCLC).

Materials And Methods: This randomized phase II trial enrolled patients with advanced or metastatic NSCLC after first line chemotherapy.

A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COU-AA-301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.

Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs.

Farmers' perception and adaptation practice to climate variability and change: a case study of the Vea catchment in Ghana.

Background: Rain-fed agriculture remains the source of employment for a majority of Ghana's population, particularly in northern Ghana where annual rainfall is low. The purpose of this study is to examine farmers' perceptions and adaptation practices to climate change and variability in accordance with actual recorded weather data of the Vea catchment in Upper East Region of northern Ghana during the time interval from 1972 to 2012.

Methods: Climatic data over 41-years (1972-2012) from four stations in vicinity of the catchment was evaluated to identify actual weather outcomes.

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.

Background: Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.

Methods: A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken.

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

Background: Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts.

Methods And Results: Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks.

Mechanisms of phrenic nerve injury during radiofrequency ablation at the pulmonary vein orifice.

Background: The phrenic nerve can be injured with radiofrequency energy delivery. Nevertheless, the mechanisms of injury are unknown. This study was undertaken to examine phrenic nerve tissue temperatures during ablation at the pulmonary vein (PV) orifice, assess the temperature dependence of injury, and to delineate the possible mechanisms of untoward nerve effects.

Efficacy and safety of circumferential pulmonary vein isolation using a novel cryothermal balloon ablation system.

Objectives: We sought to evaluate the efficacy and safety of a novel cryothermal balloon ablation system in creating pulmonary vein (PV) isolation.

Background: Pulmonary vein isolation using standard radiofrequency ablation techniques is limited by procedure-related complications, such as thrombus formation and PV stenosis. Cryothermal ablation may reduce the risk of such complications.

Discrepancies between catheter tip and tissue temperature in cooled-tip ablation: relevance to guiding left atrial ablation.

Background: It is not known whether catheter tip temperatures with a cooled-tip ablation can be reliably extrapolated to estimate actual tissue temperatures. The relationship between catheter tip temperatures, tissue temperatures, power, and microbubble formation is not known.

Methods And Results: Nine dogs underwent 111 radiofrequency energy deliveries at the pulmonary vein ostia with a cooled-tip catheter.

Prediction of short- and long-term outcomes by electrocardiography in survivors of out-of-hospital cardiac arrest.

Background: Programs focusing on early defibrillation have improved both short- and long-term survival of patients with VF out-of-hospital cardiac arrest (OHCA). Subsequent long-term management of survivors would be facilitated by a straight-forward, non-invasive method of identifying those at highest risk for recurrence. Therefore, we assessed the predictive value of the standard ECG to determine both short- and long-term outcomes in survivors of VF OHCA to assist in risk stratification of those patients at highest risk of sudden death.

Analysis of catheter-tip (8-mm) and actual tissue temperatures achieved during radiofrequency ablation at the orifice of the pulmonary vein.

Background: Many ablative approaches in or near the orifice of the pulmonary vein (PV) have demonstrated success in eliminating atrial fibrillation. Despite current practice, there are no data regarding the in vivo efficacy and safety of an 8-mm catheter tip for ablation at the PV orifice.

Methods And Results: Ten mongrel dogs were studied.

Measurement of the anticancer agent gemcitabine and its deaminated metabolite at low concentrations in human plasma by liquid chromatography-mass spectrometry.

A liquid chromatography/mass spectrometry (LC-MS) method has been developed and validated for the determination of the anticancer agent gemcitabine (dFdC) and its metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) in human plasma. An Oasis((R)) HLB solid phase extraction cartridge was used for plasma sample preparation. Separation of the analytes was achieved with a YMC ODS-AQ (5 microm, 120 A, 2.

Eosinophilic-lymphocytic myocarditis after smallpox vaccination.

Smallpox is an eradicated viral disease that has re-emerged as a potential bioterrorism threat. Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option.

A phase I and pharmacologic study of weekly gemcitabine in combination with infusional 5-fluorodeoxyuridine and oral calcium leucovorin.

Purpose: Since preclinical studies have shown more than additive cytotoxicity and DNA damage with the combination of gemcitabine and 5-fluoro-2'-deoxyuridine (FUDR), we studied this combination in a phase I trial.

Methods: Gemcitabine alone was given in cycle 1 as a 24-h, 2-h or 1-h i.v.

Measurement of the anti-cancer agent gemcitabine in human plasma by high-performance liquid chromatography.

A reversed-phase HPLC assay has been developed to determine the concentration of the anti-metabolite 2',2'-difluorodeoxycytidine (gemcitabine, dFdC) in human plasma over the concentration range of 0.5-150 microM (0.13-39.

Subsets more likely to benefit from surgery or prophylactic cranial irradiation after chemoradiation for localized non-small-cell lung cancer.

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful.

A phase I pharmacologic and pharmacodynamic study of pyrazoloacridine given as a weekly 24-hour continuous intravenous infusion in adult cancer patients.

Purpose: Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases I and II through a mechanism distinct from other topoisomerase poisons. PZA shows schedule-independent cytotoxicity against tumor cells, whereas host toxicity is greater with shorter infusions. We assessed the clinical toxicities and pharmacologic effects of PZA given as a 24-h i.

Impact of two weekly schedules of oral eniluracil given with fluorouracil and leucovorin on the duration of dihydropyrimidine dehydrogenase inhibition.

Purpose: This study determined the effect of different weekly dosing schedules of 5-fluorouracil (5-FU)/leucovorin (LV)/eniluracil on dihydropyrimidine dehydrogenase (DPD) activity and plasma uracil levels.

Methods: Plasma and mononuclear cells were isolated from peripheral blood samples obtained before, during, and at various times after 5-FU/LV/eniluracil therapy. Two schedules were studied: 20 mg of eniluracil p.