Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Characterization of a terbium activated gadolinium oxysulfide plastic optical fibre sensor in photons and protons

A characterization study was carried out to determine if a novel, millimeter sized Terbium-activated Gadolinium Oxysulfide optical fibre detector has potential for future use in proton dosimetry. Preliminary studies employed a Theratronics Theratron 780C Cobalt-60 unit and were used to determine nominal dose response, field size response and. Cerenkov contributions in 1.25-MeV gamma radiation. More extensive testing was done using 74 MeV-protons produced in the TRIUMF 500-MeV cyclotron facility examining raw Bragg peak, spread out Bragg peak, dose response, and. Cerenkov signal. The detector was low-cost and easily assembled; it showed excellent sensitivity, signal to noise ratio, and reproducibility. Quenching at high linear energy transfer was severe. Additional investigations are needed to further explore Cerenkov-only depth-dose curves, signal detection at the extreme distal end of the Bragg peak, and possible sensitivity to neutrons

Validation of a Patient-Reported Outcome Measure for Moist Desquamation among Breast Radiotherapy Patients

There has been an increasing interest in patient-reported outcome (PRO) measures in both the clinical and research settings to improve the quality of life among patients and to identify when clinical intervention may be needed. The primary purpose of this prospective study was to validate an acute breast skin toxicity PRO measure across a broad sample of patient body types undergoing radiation therapy. Between August 2018 and September 2019, 134 women undergoing adjuvant breast radiotherapy (RT) consented to completing serial PRO measures both during and post-RT treatment and to having their skin assessed by trained trial radiation therapists. There was high patient compliance, with 124 patients (92.5%) returning to the clinic post-RT for at least one staff skin assessment. Rates of moist desquamation (MD) in the infra-mammary fold (IMF) by PRO were compared with skin assessments completed by trial radiation therapists. There was high sensitivity (86.5%) and good specificity (79.4%) between PRO and staff-reported presence of MD in the IMF, and there was a moderate correlation between the peak severity of the MD reported by PRO and assessed by staff (rho = 0.61, p < 0.001). This prospective study validates a new PRO measure to monitor the presence of MD in the IMF among women receiving breast RT.Medicine, Faculty ofScience, Faculty ofNon UBCMedical Oncology, Division ofPhysics and Astronomy, Department ofPopulation and Public Health (SPPH), School ofSurgery, Department ofReviewedFacultyResearche

Potential of Novel Optical Fibers for Proton Therapy Dosimetry

International audienc

novel Gd 3+ -doped silica-based optical fiber material for dosimetry in proton therapy

International audienceOptical fibers hold promise for accurate dosimetry in small field proton therapy due to their superior spatial resolution and the lack of significant Cerenkov contamination in proton beams. One known drawback for most scintillation detectors is signal quenching in areas of high linear energy transfer, as is the case in the Bragg peak region of a proton beam. In this study, we investigated the potential of innovative optical fiber bulk materials using the sol-gel technique for dosimetry in proton therapy. This type of glass is made of amorphous silica (SiO 2) and is doped with Gd 3+ ions and possesses very interesting light emission properties with a luminescence band around 314 nm when exposed to protons. The fibers were manufactured at the University of Lille and tested at the TRIUMF Proton Therapy facility with 8.2-62.9 MeV protons and 2-6 nA of extracted beam current. Dose-rate dependence and quenching were measured and compared to other silica-based fibers also made by sol-gel techniques and doped with Ce 3+ and cu +. The three fibers present strong luminescence in the UV (Gd) or visible (Cu,Ce) under irradiation, with the emission intensities related directly to the proton flux. In addition, the 0.5 mm diameter Gd 3+-doped fiber shows superior resolution of the Bragg peak, indicating significantly reduced quenching in comparison to the Ce 3+ and cu + fibers with a Birks' constant, k B , of (0.0162 ± 0.0003) cm/MeV in comparison to (0.0333 ± 0.0006) cm/MeV and (0.0352 ± 0.0003) cm/MeV, respectively. To our knowledge, this is the first report of such an interesting k B for a silica-based optical fiber material, showing clearly that this fiber presents lower quenching than common plastic scintillators. This result demonstrates the high potential of this inorganic fiber material for proton therapy dosimetry