A phase 1b randomised,placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma

Background Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.Methods Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored.Results The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.Conclusions With personalised dosing, nabiximols had acceptable safety and tolerability with no drug–drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial.Clinical trial registration ClinicalTrials.gov: Part 1– NCT01812603; Part 2– NCT01812616.Subject terms: CNS cancer, Drug development, CNS cancer, Pharmaceutics     

An Evaluation of Spin in Lower Extremity Joint Trials

Background

Spin is a specific type of reporting bias that misrepresents data and results within randomized controlled trials (RCTs). Because spin may provide a surgeon with an inaccurate representation of trial results, thus misconstruing the surgeons' interpretation thereof and possibly negatively affecting patient care, it is important that spin is identified within publications. The primary goal of our study was to determine the prevalence of spin found within the abstracts of lower extremity joint trials.

Regional anaesthesia in patients taking anticoagulant drugs

Many surgical patients are taking drugs that impair normal coagulation, and this causes concern about the risk of perioperative bleeding events. The anaesthetist is particularly concerned about compressive vertebral canal haematomas that may occur after spinal or epidural anaesthetic techniques. Fortunately, the risk of this complication is very low. The major risk factors are coagulopathy or technical difficulties with the block. There is also concern about perineural haematomas that may be associated with peripheral nerve blocks. This article attempts to put the risks of these complications into context, with reference to different classes of anticoagulant drugs.     

Seven-year outcome following Colles' type distal radial fracture. A comparison of two treatment methods

Eighty-five patients were reviewed 7 years after prospective randomization to bridging external fixation or plaster immobilization for treatment of a Colles' type distal radial fracture. The Gartland and Werley score showed that most patients in each group had an excellent or good outcome and patient satisfaction was comparable and high in both groups. The fixator group had significantly less radial shortening (P<0.05). Despite a high level of radiographic malunion (50%) overall function, range of movement and activities of daily living were not limited. Twenty-five per cent of patients had minor radiological signs of post-traumatic arthritis although only one patient was symptomatic. We conclude that, in the long term, external fixation of distal radius fractures does not confer an improved outcome when compared to plaster immobilization.