The historical origins of modern international normalized ratio targets.

Prothrombin time (PT) and its derivative international normalized ratio (INR) are frequently ordered to assess the coagulation system. Plasma transfusion to treat incidentally abnormal PT/INR is a common practice with low biological plausibility and without credible evidence, yet INR targets appear in major clinical guidelines and account for the majority of plasma use at many institutions. In this article, we review the historical origins of INR targets. We recount historical milestones in the development of the PT, discovery of vitamin K antagonists (VKAs), motivation for INR standardization, and justification for INR targets in patients receiving VKA therapy. Next, we summarize evidence for INR testing to assess bleeding risk in patients not on VKA therapy and plasma transfusion for treating mildly abnormal INR to prevent bleeding in these patients. We conclude with a discussion of the parallels in misunderstanding of historic PT and present-day INR testing with lessons from the past that might help rationalize plasma transfusion in the future.

Leading digit bias in hemoglobin thresholds for red cell transfusion.

BACKGROUND: Leading digit bias is a heuristic whereby humans overemphasize the left-most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients. STUDY DESIGN AND METHODS: Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups. RESULTS: A total of 211,872 red cell transfusions were identified over the study period (median pre-transfusion hemoglobin 76 g/L; interquartile range = 69-92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: -1215 to -415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: -4407 to -1220), and 89 g/L showed 40 fewer units (95% CI: -408 to 328). The effect was accentuated during daytime, weekday, and May-June months, persisted in analyses including all transfusions, and was absent at control thresholds. CONCLUSION: Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi-experimental study design in transfusion research.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

BACKGROUND: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. STUDY DESIGN AND METHODS: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). RESULTS: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. CONCLUSION: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion.

Costs for Long-Term Health Care After a Police Shooting in Ontario, Canada.

Importance: Police shootings can cause serious acute injury, and knowledge of subsequent health outcomes may inform interventions to improve care. Objective: To analyze long-term health care costs among survivors of police shootings compared with those surviving nonfirearm police enforcement injuries using a retrospective design. Design, Setting, and Participants: This population-based cohort analysis identified adults (age ≥16 years) who were injured by police and required emergency medical care between April 1, 2002, and March 31, 2022, in Ontario, Canada. Exposure: Police shootings compared with other mechanisms of injury involving police. Main Outcomes and Measures: Long-term health care costs determined using a validated costing algorithm. Secondary outcomes included short-term mortality, acute care treatments, and rates of subsequent disability. Results: Over the study, 13 545 adults were injured from police enforcement (mean [SD] age, 35 [12] years; 11 637 males [86%]). A total of 13 520 individuals survived acute injury, and 8755 had long-term financial data available (88 surviving firearm injury, 8667 surviving nonfirearm injury). Patients surviving firearm injury had 3 times greater health care costs per year (CAD$16 223 vs CAD$5412; mean increase, CAD$9967; 95% CI, 6697-13 237; US $11 982 vs US $3997; mean increase, US $7361; 95% CI, 4946-9776; P < .001). Greater costs after a firearm injury were not explained by baseline costs and primarily reflected increased psychiatric care. Other characteristics associated with increased long-term health care costs included prior mental illness and a substance use diagnosis. Conclusions and Relevance: In this longitudinal cohort study of long-term health care costs, patients surviving a police shooting had substantial health care costs compared with those injured from other forms of police enforcement. Costs primarily reflected psychiatric care and suggest the need to prioritize early recognition and prevention.

Therapeutic plasma exchange in alloimmune platelet refractoriness.

Patients with alloimmune platelet refractoriness can present complex clinical conundrums. Herein we describe a case of platelet refractoriness in the setting of combined HLA and HPA alloimmunization in a patient with acute myeloid leukemia and life-threatening bleeding. We discuss causative antibodies and compare prevailing therapeutic modalities. We highlight plasma exchange as a potentially feasible, repeatable, and personalized treatment option for patients with extensive platelet alloimmunization who require transfusion.

Reducing redundant creatine kinase testing in cardiac injury.

BACKGROUND: Creatine kinase (CK) testing in the setting of suspected cardiac injury is commonly performed yet rarely provides clinical value beyond troponin testing. We sought to evaluate and reduce CK testing coupled with troponin testing by 50% or greater. METHODS: We performed root cause analysis to study prevailing processes and patterns of CK testing. We developed new institutional guidelines, removed CK from high-volume paper and electronic order bundles and conducted academic detailing for departments with highest ordering frequency. We evaluated consecutive patients at Sunnybrook Health Sciences Centre between 1 January 2018 and 31 March 2020 who had either a CK or troponin level measured. We prespecified successful implementation as a reduction of 50% in total CK orders and a decrease in the ratio of CK-to-troponin tests to one-third or less. We retained additional data beyond our study period to assess for sustained reductions in testing. RESULTS: Total CK tests decreased over the study period from 3963 to 2111 per month, amounting to a 46.7% reduction (95% CI 33.2 to 60.2; p<0.001) equalling 61 fewer tests per hospital day. Troponin testing did not significantly change during the intervention. Ratio of CK-to-troponin tests decreased from 0.91 to 0.49 (p<0.001). The reduction coincided with changes to order-sets, was observed across all clinical units and was sustained during additional months beyond the study period. These reductions in testing resulted in a projected annual cost savings of C$28 446. CONCLUSIONS: We demonstrate that a low-cost and feasible quality improvement initiative may lead to significant reduction in unnecessary CK testing and substantial savings in healthcare costs for patients with suspected cardiac injury.

Death and long-term disability after gun injury: a cohort analysis.

BACKGROUND: Gun injury accounts for substantial acute mortality worldwide and many others survive with lingering disabilities. We investigated whether additional health losses beyond mortality can also arise for patients who survive with long-term disability. METHODS: We conducted a population-based individual patient analysis of adults injured by firearms who had received emergency medical care in Ontario, Canada, from Apr. 1, 2002, to Apr. 1, 2019. Longitudinal cohort analyses were evaluated through deterministic linkages of individual electronic patient files. The primary outcome was death or subsequent application for long-term disability in the years after hospital discharge. RESULTS: In total, 8313 patients were injured from firearms, of which 3020 were injured from intentional incidents and 5293 were injured from unintentional incidents. A total of 2657 (88.0%) patients with intentional gun injury and 5089 (96.1%) patients with unintentional gun injury survived initial injuries. After a mean 7.75 years of follow-up, patients surviving intentional injuries had a disability rate twice as high as patients surviving unintentional injuries (19.7% v. 10.1%, p < 0.001), equivalent to a hazard ratio of 2.01 (95% confidence interval 1.80-2.25). The higher risk of long-term disability for survivors after intentional gun injury was not explained by demographic characteristics, extended to survivors treated and released from the emergency department, and was observed regardless of whether the incident was self-inflicted or from interpersonal assault. Half of the disability cases were identified after the first year. Additional predictors of long-term disability included a lower socioeconomic status, an urban home location, arrival by ambulance transport, a history of mental illness and a diagnosis of substance use disorder. INTERPRETATION: Our study shows that gun death statistics underestimate the extent of health losses from long-term disability, particularly for those with intentional injuries. Additional and sustainable follow-up medical care might improve patient outcomes.

Optical illusions and life-threatening traffic crashes: A perspective on aerial perspective.

Aerial perspective illusion is a feature of visual perception where landscapes appear relatively close in clear light and distant in dim light. We hypothesized that bright sunlight might cause drivers to perceive distant terrain as relatively close and misinterpret the approach speed of surrounding landscape as unduly slow. This hypothesis would mean, in turn, that drivers in bright sunlight may underestimate their progress on the road, compensate by traveling at a faster baseline speed, and ultimately increase the prevailing risk of a life-threatening traffic crash. We conducted three pilot studies to illustrate how the illusion might contribute to a life- threatening traffic crash. The first illustration used a questionnaire to demonstrate that most respondents were mistaken when judging the distance between simple balls in different positions. The second illustration involved an experimental manipulation to assess whether aerial perspective influenced judgments about the relative positions of vehicles in traffic. The third illustration analyzed a segment of high-volume fast-speed traffic and found an increased frequency of speeding under bright sunlight. Together with past work based on the visual arts, these examples illustrate how an aerial perspective illusion can affect distance perception, may appear in realistic traffic situations, and could potentially contribute to the risk of a life-threatening traffic crash. An awareness of this hypothesis might lead to applications on how optical illusions could extend to everyday traffic and might potentially inform safety warnings to prevent life- threatening crashes.

Life-threatening motor vehicle crashes in bright sunlight.

Bright sunlight may create visual illusions that lead to driver error, including fallible distance judgment from aerial perspective. We tested whether the risk of a life-threatening motor vehicle crash was increased when driving in bright sunlight.This longitudinal, case-only, paired-comparison analysis evaluated patients hospitalized because of a motor vehicle crash between January 1, 1995 and December 31, 2014. The relative risk of a crash associated with bright sunlight was estimated by evaluating the prevailing weather at the time and place of the crash compared with the weather at the same hour and location on control days a week earlier and a week later.The majority of patients (n = 6962) were injured during daylight hours and bright sunlight was the most common weather condition at the time and place of the crash. The risk of a life-threatening crash was 16% higher during bright sunlight than normal weather (95% confidence interval: 9-24, P < 0.001). The increased risk was accentuated in the early afternoon, disappeared at night, extended to patients with different characteristics, involved crashes with diverse features, not apparent with cloudy weather, and contributed to about 5000 additional patient-days in hospital. The increased risk extended to patients with high crash severity as indicated by ambulance involvement, surgical procedures, length of hospital stay, intensive care unit admission, and patient mortality. The increased risk was not easily attributed to differences in alcohol consumption, driving distances, or anomalies of adverse weather.Bright sunlight is associated with an increased risk of a life-threatening motor vehicle crash. An awareness of this risk might inform driver education, trauma staffing, and safety warnings to prevent a life-threatening motor vehicle crash. LEVEL OF EVIDENCE: Epidemiologic Study, level III.

Concussions and Repercussions.

In their Perspective, Donald A. Redelmeier and Sheharyar Raza discuss the significance of Seena Fazel and colleagues' longitudinal study of traumatic brain injury (TBI)-associated outcomes.