The evaluation of midazolam on head injured patients in the prehospital setting

Midazolam (Hypnovel ®) is the only sedating agent used by paramedics at St John Ambulance Service W.A. in the management of many conditions including seizure activities, antisocial or uncontrollable behaviours, back pain incidents and head injuries. Midazolam, with a rapid absorption, fast onset of action and short duration on neurological activity, has been accepted as a safe and effective agent in prehospital treatment since the late-1990s. Often, if a patient is not complying with treatment or is uncontrollable or aggressive, paramedics are required to sedate the individual. This study primarily examines the use of midazolam for the sedation of unmanageable patients who have sustained a head injury in a prehospital setting. The research investigated whether midazolam (n=49) increases the symptoms of hypotension and hypoxia in patients with head injuries in a prehospital selling. Patients that sustained a head injury but did not receive midazolam (n=47) were used as controls. Physiological parameters including blood pressure, pulse and respiration rates, oxygen saturation, along with Coma Scale and Visual Analogue Scale were placed into SPSS analysis package and Excel t-tests. Further analysis on sub divided cohorts of gender, age and severity of head injury was conducted. Results indicated that although significance differences were present, midazolam did not influence hypotension or hypoxia in head injured patients. However the nature of the head injury along with behavioural issues was the result of increased symptoms of hypotension and hypoxia

Advances in personalized targeted treatment of metastatic melanoma and non-invasive tumor monitoring

Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved theway for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time.We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management

Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma

Background: New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.Methods: CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.Results: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.Conclusions: Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment