Estimation of Simulated Blood Loss by Orthopaedic Residents Before and After Brief Training

Background: Accurate estimation of blood loss (EBL) may be helpful for patient safety during certain operative procedures; however, medical students and residents are rarely instructed in EBL. In a series of two tests, we attempted to reveal any significant improvement in accuracy of EBL after a brief training session. Methods: Fourteen orthopaedic residents were recruited. Participants estimated the amounts of simulated blood before and after a training session that involved a visual of 110 cm3 of the spilled fluid. Three volumes of 50, 237, and 531 cm3 of simulated blood were spilled on a lap sponge, blanket, and trash bag, creating nine stations total for estimating blood loss. Results: The EBL for each surface was inaccurate, particularly on the absorbent material (ie, sponge and blanket). Of the 126 initial estimates, a total of 13 (10%) were within 20% of the true value. After a brief training session, a total of 43 estimates (34%) were within 20% of the true value spilled. Individual estimates maintained a wide range in both tests. Conclusions: Although EBL is a difficult skill to learn, training may result in significant improvement of accuracy. Healthcare professionals should be aware of the complications in estimating blood loss and possible benefits of formal instruction

Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors

International audienceImportance: Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data.Objective: To determine the spectrum, timing, and clinical features of fatal ICI-associated toxic effects.Design, setting, and participants: We retrospectively queried a World Health Organization (WHO) pharmacovigilance database (Vigilyze) comprising more than 16 000 000 adverse drug reactions, and records from 7 academic centers. We performed a meta-analysis of published trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) to evaluate their incidence using data from large academic medical centers, global WHO pharmacovigilance data, and all published ICI clinical trials of patients with cancer treated with ICIs internationally.Exposures: Anti-CTLA-4 (ipilimumab or tremelimumab), anti-PD-1 (nivolumab, pembrolizumab), or anti-PD-L1 (atezolizumab, avelumab, durvalumab).Main outcomes and measures: Timing, spectrum, outcomes, and incidence of ICI-associated toxic effects.Results: Internationally, 613 fatal ICI toxic events were reported from 2009 through January 2018 in Vigilyze. The spectrum differed widely between regimens: in a total of 193 anti-CTLA-4 deaths, most were usually from colitis (135 [70%]), whereas anti-PD-1/PD-L1-related fatalities were often from pneumonitis (333 [35%]), hepatitis (115 [22%]), and neurotoxic effects (50 [15%]). Combination PD-1/CTLA-4 deaths were frequently from colitis (32 [37%]) and myocarditis (22 [25%]). Fatal toxic effects typically occurred early after therapy initiation for combination therapy, anti-PD-1, and ipilimumab monotherapy (median 14.5, 40, and 40 days, respectively). Myocarditis had the highest fatality rate (52 [39.7%] of 131 reported cases), whereas endocrine events and colitis had only 2% to 5% reported fatalities; 10% to 17% of other organ-system toxic effects reported had fatal outcomes. Retrospective review of 3545 patients treated with ICIs from 7 academic centers revealed 0.6% fatality rates; cardiac and neurologic events were especially prominent (43%). Median time from symptom onset to death was 32 days. A meta-analysis of 112 trials involving 19 217 patients showed toxicity-related fatality rates of 0.36% (anti-PD-1), 0.38% (anti-PD-L1), 1.08% (anti-CTLA-4), and 1.23% (PD-1/PD-L1 plus CTLA-4).Conclusions and relevance: In the largest evaluation of fatal ICI-associated toxic effects published to date to our knowledge, we observed early onset of death with varied causes and frequencies depending on therapeutic regimen. Clinicians across disciplines should be aware of these uncommon lethal complications