Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke

Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke.

Treatment of proximal interphalangeal joint flexion contracture: Combined static and dynamic orthotic intervention compared with other therapy intervention: randomized controlled trial

Purpose To test the effectiveness of static and dynamic orthoses using them as an exclusive treatment for proximal interphalangeal (PIP) joint flexion contracture compared with other hand therapy conservative treatments described in the literature. Methods 60 patients who used orthoses were compared with a control group that received other hand therapy treatments. Clinical assessments were measured before the experiment and 3 months after and included active PIP joint extension and function. Results A significant improvement in the extension active range of motion at the PIP joint in the second measurement was found in both groups, but it was significantly greater in the experimental group. Improvement in function (Disabilities of the Arm, Shoulder, and Hand score) between the first and second assessment was similar in the control and experimental groups. Conclusions Using night progressive static and daily dynamic orthoses as an exclusive treatment during the proliferative phase led to significant improvements in the PIP joint active extension, but the improvement did not correlate with increased function as perceived by the patient.

Changes in white matter connectivity following therapy for anomia post stroke

Background. The majority of studies investigating the neural mechanisms underlying treatment-induced recovery in aphasia have focused on the cortical regions associated with language processing. However, the integrity of the white matter connecting these regions may also be crucial to understanding treatment mechanisms. Objective. This study investigated the integrity of the arcuate fasciculus (AF) and uncinate fasciculus (UF) before and after treatment for anomia in people with aphasia. Method. Eight people with aphasia received 12 treatment sessions to improve naming; alternating between phonologically-based and semantic-based tasks, with high angular resolution diffusion imaging conducted pre and post treatment. The mean generalized fractional anisotropy (GFA), a measure of fiber integrity, and number of fibers in the AF and UF were compared pre and post treatment, as well as with a group of 14 healthy older controls. Results. Pre treatment, participants with aphasia had significantly fewer fibers and lower mean GFA in the left AF compared with controls. Post treatment, mean GFA increased in the left AF to be statistically equivalent to controls. Additionally, mean GFA in the left AF pre and post treatment positively correlated with maintenance of the phonologically based treatment. No differences were found in the right AF, or the UF in either hemisphere, between participants with aphasia and controls, and no changes were observed in these tracts following treatment. Conclusions. Anomia treatments may improve the integrity of the white matter connecting cortical language regions. These preliminary results add to the understanding of the mechanisms underlying treatment outcomes in people with aphasia post stroke.

Interplay of MLC, gantry and respiratory motion during DCAT delivery

This study investigated the possible interplay effects arising from the treatment of moving targets using the dynamic conformal arc therapy (DCAT) technique. Dose from a modulated test beam was measured, with and without phantom motion and with and without a 30o arc rotation, using a diode array placed on a sinusoidally moving platform. Measurements were repeated at five different collimator angles (0, 22.5, 45, 67.5 and 90o), at two different dose rates (300 and 600 MU/min). Results showed that the effect of respiratory motion on the measured dose distribution increased slightly when the beams were delivered as arcs, rather than with a static gantry angle, and that this effect increased substantially as the collimator angle was increased from 0o (MLC motion perpendicular to respiratory motion) to 90o (MLC motion parallel to respiratory motion). The dose oscillations arising from interplay between phantom and MLC motion were found to increase in magnitude when the dose rate was increased. These results led to the development of simple recommendations for minimizing the negative effects of motion interplay on DCAT dose distributions

Investigation of the relationship between BMI and prostate motion in radiation therapy treatment for prostate cancer

This thesis studied the influence of patient obesity on prostate motion during radiation therapy treatment delivery, an important consideration in the accurate treatment of prostate cancer. The study highlighted the importance of daily image guidance to correct for prostate motion, increasing radiation dose to the prostate while decreasing radiation dose to surrounding healthy tissues, thereby increasing patient quality of life.

To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

Adverse effects of androgen-deprivation therapy in prostate cancer and their management

Objective To provide an up-to-date summary of current literature on the management of adverse effects of androgen-deprivation therapy (ADT). Patients and Methods All relevant medical literature on men with prostate cancer treated with ADT from 2005 to 2014, and older relevant papers, were reviewed. Recent health advisory statements from the Australian government, societies and advocacy groups have been incorporated to the document. Results There are numerous adverse effects of ADT that require pro-active prevention and treatment. Ranging from cardiovascular disease, diabetes and osteoporosis, to depression, cognitive decline and sexual dysfunction, the range of adverse effects is wide. Baseline assessment, monitoring, prevention and consultation from a multidisciplinary team are important in minimising the harm from ADT. Conclusions This review provides a series of practical recommendations to assist with managing the adverse effects of ADT.

A virtual radiation therapy workflow training simulation

Aim Simulation forms an increasingly vital component of clinical skills development in a wide range of professional disciplines. Simulation of clinical techniques and equipment is designed to better prepare students for placement by providing an opportunity to learn technical skills in a “safe” academic environment. In radiotherapy training over the last decade or so this has predominantly comprised treatment planning software and small ancillary equipment such as mould room apparatus. Recent virtual reality developments have dramatically changed this approach. Innovative new simulation applications and file processing and interrogation software have helped to fill in the gaps to provide a streamlined virtual workflow solution. This paper outlines the innovations that have enabled this, along with an evaluation of the impact on students and educators. Method Virtual reality software and workflow applications have been developed to enable the following steps of radiation therapy to be simulated in an academic environment: CT scanning using a 3D virtual CT scanner simulation; batch CT duplication; treatment planning; 3D plan evaluation using a virtual linear accelerator; quantitative plan assessment, patient setup with lasers; and image guided radiotherapy software. Results Evaluation of the impact of the virtual reality workflow system highlighted substantial time saving for academic staff as well as positive feedback from students relating to preparation for clinical placements. Students valued practice in the “safe” environment and the opportunity to understand the clinical workflow ahead of clinical department experience. Conclusion Simulation of most of the radiation therapy workflow and tasks is feasible using a raft of virtual reality simulation applications and supporting software. Benefits of this approach include time-saving, embedding of a case-study based approach, increased student confidence, and optimal use of the clinical environment. Ongoing work seeks to determine the impact of simulation on clinical skills.

Practice patterns of radiation therapy technology in Australia: Results of a national audit

This article presents the results of a single-day census of radiation therapy (RT) treatment and technology use in Australia. The primary aim of the study was to ascertain patterns of RT practice and technology in use across Australia. These data were primarily collated to inform curriculum development of academic programs, thereby ensuring that training is matched to workforce patterns of practice. Methods: The study design was a census method with all 59 RT centres in Australia being invited to provide quantitative summary data relating to patient case mix and technology use on a randomly selected but common date. Anonymous and demographic-free data were analysed using descriptive statistics. Results: Overall data were provided across all six Australian States by 29 centres of a possible 59, yielding a response rate of 49% and representing a total of 2743 patients. Findings from this study indicate the increasing use of emerging intensity-modulated radiotherapy (IMRT), image fusion and image-guided radiation therapy (IGRT) technology in Australian RT planning and delivery phases. IMRT in particular was used for 37% of patients, indicating a high uptake of the technology in Australia when compared to other published data. The results also highlight the resource-intensive nature of benign tumour radiotherapy. Conclusions: In the absence of routine national data collection, the single-day census method offers a relatively convenient means of measuring and tracking RT resource utilisation. Wider use of this tool has the potential to not only track trends in technology implementation but also inform evidence-based guidelines for referral and resource planning.

Factors influencing radiation therapy student clinical placement satisfaction

Introduction Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning.

Evaluation of a school-based creative arts therapy programme for adolescents from refugee backgrounds

Creative arts therapy programs have been identified as effective interventions with adolescents affected by adversity. The current study provided a controlled trial of creative arts therapy to address the psychosocial needs of students from refugee backgrounds. Forty-two students participated in a therapy trial, comprising an intervention and control group. Mental health and behavioural difficulties were assessed pre and post intervention. Hopkins Symptoms Checklist-25 (HSCL-25) and the Strengths and Difficulties Questionnaire (SDQ) were used to assess wellbeing. Findings suggested an effect for a reduction in behavioural difficulties for the treatment group. A significant reduction in emotional symptoms was found for the treatment group. Findings provide empirical support for school-based creative arts therapy interventions specific to refugee young people.

De novo combination therapy adefovir plus lamivudine as a treatment for women of child-bearing age with HBeAg-positive chronic hepatitis B before pregnancy

Substantial progress has been achieved in antiviral therapy for chronic hepatitis B; however, options for women of child-bearing age with HBeAg-positive chronic hepatitis B remain a challenge. In this study, we sought to determine whether de novo combination therapy of Adefovir plus Lamivudine was a super treatment for women of child-bearing age with HBeAg-positive chronic hepatitis B prior to conception. A total of 122 women patients of child-bearing age with HBeAg-positive chronic hepatitis B were randomly assigned to receive (i) 10 mg Adefovir plus 100 mg Lamivudine (64 patients) or (ii) 10 mg Adefovir monotherapy (58 patients), administrated orally once daily for 96 weeks. The therapeutic efficacy within each group was compared at weeks 48 and 96. The results showed that de novo combination therapy of Adefovir plus Lamivudine significantly reduced HBV-DNA detectability, and enhanced ALT normalization and HBeAg seroconversion in women of child-bearing age with HBeAg-positive chronic hepatitis B. No virological breakthrough and genotypic resistance were observed in the combination therapy group. Additionally, the combination therapy with Adefovir plus Lamivudine was well tolerated. This study suggests that de novo combination therapy of Adefovir plus Lamivudine offers a therapeutic advantage for women of child-bearing age with HBeAg-positive chronic hepatitis B when taken before conception.

Dietary and exercise interventions to improve quality of life, metabolic risk factors and androgen deficiency symptoms in men with prostate cancer undergoing androgen deprivation therapy

Introduction Lifestyle interventions might be useful in the management of adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. Objectives To examine the effects of dietary and exercise interventions on quality of life (QoL), metabolic risk factors and androgen deficiency symptoms in men with prostate cancer undergoing ADT. Methods CINAHL, Cochrane library, Medline and PsychINFO were searched to identify randomised controlled trials published from January, 2004 to October, 2014. Data extraction and methodological quality assessment was independently conducted by two reviewers. Meta-analysis was conducted using RevMan® 5.3.5. Results Of 2183 articles retrieved, 11 studies met the inclusion criteria and had low risk of bias.Nine studies evaluated exercise (resistance and/or aerobic and/or counselling) and three evaluated dietary supplementation. Median sample size =79 (33–121) and median intervention duration was 12 weeks (12–24). Exercise improved QoL measures (SMD 0.26, 95%CI −0.01 to 0.53) but not body composition, metabolic risk or vasomotor symptoms. Qualitative analysis indicated soy (or isoflavone) supplementation did not improve vasomotor symptoms; however, may improve QoL. Conclusions Few studies have evaluated the efficacy of lifestyle interventions in the management of adverse effects of ADT. We found inconclusive results for exercise in improving QoL and negative results for other outcomes. For soy-based products, we found negative results for modifying vasomotor symptoms and inconclusive results for improving QoL. Future work should investigate the best mode of exercise for improving QoL and other interventions such as dietary counselling should be investigated for their potential to modify these outcomes.

Successful topical tacrolimus (FK506) therapy in a child with pyoderma gangrenosum

The inflammatory skin disease pyoderma gangrenosum is characterized by destructive ulceration, typically occurring on the calves and thighs and less commonly on the buttocks and face. Lesions vary in size and may be multiple, often rapidly ulcerating to form deep painful wounds. Ulcers characteristically have ragged purple edges that overhang. In many patients a concomitant condition can be identified such as inflammatory bowel disease, rheumatoid arthritis, chronic autoimmune hepatitis, and various hematologic and solid tumours (1,2). Treatment of these ulcers in the past has been disappointing. The large lesions usually run a chronic course and heal very slowly, with traditional dressings often in combination with systemic steroids or immunosuppressants. Since 1998, a small number of case have been reported of adults with pyoderma gangrenosum whose lesions heal with the use of topical tacrolimus (FK506) (2–4). We report, to the best of our knowledge, the first successful treatment of a child with pyoderma gangrenosum using topical tacrolimus.