Interruptions are an inevitable, and often negative, part of everyday life that increase both errors and the time needed to complete even menial tasks. However, existing research suggests that being ...given time to prepare for a pending interruption-a lag time-can mitigate some of the interruption costs. To understand better why interruption lags are effective, we present a series of three experiments in which we develop and test a novel sequential decision-making paradigm, the mazing race. We find that interruption lags were only beneficial when participants had a clear strategy for how to complete the task, allowing them to avoid specific errors. In the final experiment, we attempted to use what we learned about the kinds of errors introduced by interruptions to develop a feedback-based intervention, aimed at dealing with situations in which interruption lags are not possible. We found that feedback was, only in certain situations, an effective replacement for an interruption lag. Overall, however, because the usefulness of interruption lags depend on the specific strategy a participant adopts, developing generic interventions to replace interruption lags is likely to be difficult.
Public Significance Statement
We argue that having time to prepare for an impending interruption (i.e., an "interruption lag") can reduce its negative impact, particularly when one has a clear strategy for what needs to be remembered during that time. We also conclude that it is not trivial to replace these so-called interruption lags with information that might have been forgotten during an interruption, because individuals use this time in a variety of ways, remembering whatever information they believe is necessary for their specific way of solving a problem.
Jointly initiated by Monash Children's and The Royal Children's Hospital (RCH), The Victorian Children's Tool for Observation and Response project, known as ViCTOR is a sector-led project funded by ...the Victorian Paediatric Clinical Network.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Interruptions are an inevitable occurrence in health care. Interruptions in diagnostic decision-making are no exception and can have negative consequences on both the decision-making process and ...well-being of the decision-maker. This may result in inaccurate or delayed diagnoses. To date, research specific to interruptions on diagnostic decision-making has been limited, but strategies to help manage the negative impacts of interruptions need to be developed and implemented. In this perspective, we first present a modified model of interruptions to visualize the interruption process and illustrate where potential interventions can be implemented. We then consider several empirically tested strategies from the fields of health care and cognitive psychology that can lay the groundwork for additional research to mitigate effects of interruptions during diagnostic decision-making. We highlight strategies to minimize the negative impacts of interruptions as well as strategies to prevent interruptions altogether. Additionally, we build upon these strategies to propose specific research priorities within the field of diagnostic safety. Identifying effective interventions to help clinicians better manage interruptions has the potential to minimize diagnostic errors and improve patient outcomes.
In three experiments, we sought to understand when and why people use an algorithm decision aid. Distinct from recent approaches, we explicitly enumerate the algorithm’s accuracy while also providing ...summary feedback and training that allowed participants to assess their own skills. Our results highlight that such direct performance comparisons between the algorithm and the individual encourages a strategy of selective reliance on the decision aid; individuals ignored the algorithm when the task was easier and relied on the algorithm when the task was harder. Our systematic investigation of summary feedback, training experience, and strategy hint manipulations shows that further opportunities to learn about the algorithm encourage not only increased reliance on the algorithm but also engagement in experimentation and verification of its recommendations. Together, our findings emphasize the decision-maker’s capacity to learn about the algorithm providing insights for how we can improve the use of decision aids.
Abstract
Background
Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed ...beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA
.
Methods
This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized.
Results
Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (
n
= 6/13) of patients in SAR200 + 26W, 43% (
n
= 3/7) in SAR150 + 26W, 30% (
n
= 3/10) in PBO + 52W, and 0 (
n
= 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (
n
= 6/10) in PBO + 52W and 17% (
n
= 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (
n
= 6/13, SAR200 + 26W), 43% (
n
= 3/7, SAR150 + 26W), 60% (
n
= 6/10, PBO + 52W), and 33% (
n
= 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80–100%) experienced treatment-emergent adverse events, with similar incidences reported across groups.
Conclusions
Owing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings.
Trial registration
ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.
There is great interest in relating individual differences in cognitive processing to activation of neural systems. The general process involves relating measures of task performance like reaction ...times or accuracy to brain activity to identify individual differences in neural processing. One limitation of this approach is that measures like reaction times can be affected by multiple components of processing. For instance, some individuals might have higher accuracy in a memory task because they respond more cautiously, not because they have better memory. Computational models of decision making, like the drift-diffusion model and the linear ballistic accumulator model, provide a potential solution to this problem. They can be fitted to data from individual participants to disentangle the effects of the different processes driving behavior. In this sense the models can provide cleaner measures of the processes of interest, and enhance our understanding of how neural activity varies across individuals or populations. The advantages of this model-based approach to investigating individual differences in neural activity are discussed with recent examples of how this method can improve our understanding of the brain-behavior relationship.
Highlights • A case of human parechovirus type 3 (HPeV3) myocarditis and encephalitis in an adolescent is reported. • HPeV3 infection occurred in the setting of rituximab-related ...hypogammaglobulinemia. • HPeV3 persistence for 2 years was associated with severe clinical consequences. • Complete VP1 gene sequencing revealed five unique amino acid substitutions. • Intravenous immunoglobulin therapy was followed by gradual clinical improvement.
In patients with polymyalgia rheumatica with relapse during glucocorticoid tapering, interleukin-6 receptor antagonist sarilumab increased disease remission and reduced glucocorticoid exposure at 1 ...year.
Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe ...(requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.
We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 death to 7 discharged from hospital) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021.
Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 20%), sarilumab 200 mg (n=159 38%), or sarilumab 400 mg (n=173 42%). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days 95% CI 9·0 to 15·0) and sarilumab 200 mg (10·0 days 9·0 to 12·0; hazard ratio HR 1·03 95% CI 0·75 to 1·40; log-rank p=0·96) or sarilumab 400 mg (10·0 days 9·0 to 13·0; HR 1·14 95% CI 0·84 to 1·54; log-rank p=0·34), or in proportions of patients alive (77 92% of 84 patients in the placebo group; 143 90% of 159 patients in the sarilumab 200 mg group; difference -1·7 -9·3 to 5·8; p=0·63 vs placebo; and 159 92% of 173 patients in the sarilumab 400 mg group; difference 0·2 -6·9 to 7·4; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% 95% CI -7·7 to 25·5; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group.
This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19.
Sanofi and Regeneron Pharmaceuticals.
Leukocyte interactions with vascular endothelium during inflammation depend on cascades of adhesion molecule engagement, particularly during selectin-mediated leukocyte rolling. Leukocyte rolling is ...also facilitated by members of the integrin and Ig families. Specifically, leukocyte rolling velocities during inflammation are significantly increased in ICAM-1-deficient mice, with ICAM-1 expression required for optimal P- and L-selectin-mediated rolling. Elimination of ICAM-1 expression in L-selectin-deficient mice significantly reduces leukocyte rolling. Whether disrupted leukocyte rolling in L-selectin and ICAM-1 double-deficient (L-selectin/ICAM-1-/-) mice affects leukocyte entry into sites of inflammation in vivo was assessed in the current study by using experimental models of inflammation; thioglycollate-induced peritonitis, chemokine-induced neutrophil migration to the skin, delayed-type hypersensitivity responses, rejection of allogeneic skin grafts, and septic shock. In many cases, the loss of both L-selectin and ICAM-1 expression dramatically reduced leukocyte migration into sites of inflammation beyond what was observed with loss of either receptor alone. In fact, the effects from loss of both L-selectin and ICAM-1 effectively eliminated multiple chronic inflammatory responses in L-selectin/ICAM-1-/- mice. By contrast, the combined loss of L-selectin and ICAM-1 expression had minimal effects on the generation of Ag-specific T cell responses or humoral immunity. Thus, members of the selectin and Ig families function synergistically to mediate optimal leukocyte rolling and entry into tissues, which is essential for the generation of effective inflammatory responses in vivo.
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