Predicting neurobehavioral performance of resident physicians in a Randomized Order Safety Trial Evaluating Resident-Physician Schedules (ROSTERS).

OBJECTIVES: Mathematical models of human neurobehavioral performance that include the effects of acute and chronic sleep restriction can be key tools in assessment and comparison of work schedules, allowing quantitative predictions of performance when empirical assessment is impractical. METHODS: Using such a model, we tested the hypothesis that resident physicians working an extended duration work roster, including 24-28 hours of continuous duty and up to 88 hours per week averaged over 4weeks, would have worse predicted performance than resident physicians working a rapidly cycling work roster intervention designed to reduce the duration of extended shifts. The performance metric used was attentional failures (ie, Psychomotor Vigilance Task lapses). Model input was 169 actual work and sleep schedules. Outcomes were predicted hours per week during work hours spent at moderate (equivalent to 16-20 hours of continuous wakefulness) or high (equivalent to ≥20 hours of continuous wakefulness) performance impairment. RESULTS: The model predicted that resident physicians working an extended duration work roster would spend significantly more time at moderate impairment (p = .02, effect size=0.2) than those working a rapidly cycling work roster; this difference was most pronounced during the circadian night (p < .001). On both schedules, performance was predicted to decline from weeks 1 + 2 to weeks 3 + 4 (p < .001), but the rate of decline was significantly greater on extended duration work roster (p < .01). Predicted performance impairment was inversely related to prior sleep duration (p < .001). CONCLUSIONS: These findings demonstrate the utility of a mathematical model to evaluate the predicted performance profile of schedules for resident physicians and others who experience chronic sleep restriction and circadian misalignment.

Assessing the impact of FFP3 masks to oxygen saturation and pulse rate in the Oral Surgery department at the Glasgow Dental Hospital during the COVID-19 pandemic: an observational study.

Aim: The impact on physiological parameters and well-being from potential respiratory distress caused by FFP3 masks, particularly during extensive clinical sessions, has been widely speculated during the COVID-19 pandemic. This study aims to investigate the effect of FFP3 mask wear on clinicians' pulse rate and oxygen saturation. Material & Methods: Clinical staff within the Oral Surgery department recorded their oxygen saturation (SpO2) and pulse rate prior to donning an FFP3 mask, prior to doffing FFP3 mask and after doffing FFP3 mask using a finger pulse oximeter for a two-week period in May-June 2020. The duration of wear, the session (AM/PM), the brand of mask and the presence of previous COVID-19 symptoms were also recorded. Results: Twenty-eight data sets were collected from twelve participants (1M:11F). Of the FFP3 masks worn, nineteen (67.86%) were ARCOTM, eight (28.57%) were 3MTM masks and one (3.57%) was 3M+TM. At baseline, the mean SpO2 was 98.39% and the mean pulse rate was 72.11. Prior to mask removal, the mean SpO2 was 97.82% and the mean pulse rate was 70.04. At the end of the session, the mean SpO2 was 98.14% and the mean pulse rate was 69.54. The mean duration of wear was 150.34 min. Data sets were collected evenly across AM (14) and PM (14) sessions. Five participants (17.86%) reported previous COVID-19 symptoms. Conclusion: The data demonstrated a mean reduction of 0.25% in oxygen saturation and 3.56% in pulse rate, following the use of an FFP3 mask. These changes in physiological parameters are not clinically significant and sessional use appears to be safe.

Extended Work Shifts and Neurobehavioral Performance in Resident-Physicians.

OBJECTIVES: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians. METHODS: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs. Resident-physicians worked 4-week EDWRs with shifts of 24+ hours every third or fourth shift, or an RCWR in which most shifts were ≤16 consecutive hours. Participants completed a daily sleep and work log and the 10-minute Psychomotor Vigilance Task and Karolinska Sleepiness Scale 2 to 5 times per shift approximately once per week as operational demands allowed. RESULTS: Overall, the mean (± SE) number of attentional failures was significantly higher (P =.01) on the EDWR (6.8 ± 1.0) compared with RCWR (2.9 ± 0.7). Reaction time and subjective alertness were also significantly higher, by ∼18% and ∼9%, respectively (both P <.0001). These differences were sustained across the 4-week rotation. Moreover, attentional failures were associated with resident-physician-related serious medical errors (SMEs) (P =.04). Although a higher rate of SMEs was observed under the RCWR, after adjusting for workload, RCWR had a protective effect on the rate of SMEs (rate ratio 0.48 [95% confidence interval: 0.30-0.77]). CONCLUSIONS: Performance impairment due to EDWR is improved by limiting shift duration. These data and their correlation with SME rates highlight the impairment of neurobehavioral performance due to extended-duration shifts and have important implications for patient safety.

Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors. CONCLUSIONS: Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).

Kinetic model optimization and its application to mitigating the Warburg effect through multiple enzyme alterations.

Pathway engineering is a powerful tool in biotechnological and clinical applications. However, many phenomena cannot be rewired with a single enzyme change, and in a complex network like energy metabolism, the selection of combinations of targets to engineer is a daunting task. To facilitate this process, we have developed an optimization framework and applied it to a mechanistic kinetic model of energy metabolism. We then identified combinations of enzyme alternations that led to the elimination of the Warburg effect seen in the metabolism of cancer cells and cell lines, a phenomenon coupling rapid proliferation to lactate production. Typically, optimization approaches use integer variables to achieve the desired flux redistribution with a minimum number of altered genes. This framework uses convex penalty terms to replace these integer variables and improve computational tractability. Optimal solutions are identified which substantially reduce or eliminate lactate production while maintaining the requirements for cellular proliferation using three or more enzymes.

Design and recruitment of the randomized order safety trial evaluating resident-physician schedules (ROSTERS) study.

INTRODUCTION: While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs). METHODS: ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers. The primary aim was to compare patient safety between the extended duration work roster (EDWR), which included shifts ≥24 h, and a rapidly cycling work roster (RCWR), where shifts were limited to a maximum of 16 h. Information on potential medical errors was gathered and used for classification by centrally trained physician reviewers who were blinded to the study arm. Secondary aims were to assess the relationship of the study arm to resident-physician sleep duration, work hours and neurobehavioral performance. RESULTS: The study involved 6577 patients with a total of 38,821 patient days (n = 18,749 EDWR, n = 20,072 RCWR). There were 413 resident-physician rotations included in the study (n = 203 EDWR, n = 210 RCWR). Resident-physician questionnaire data were over 95% complete. CONCLUSIONS: Results from data collected in the ROSTERS study will be evaluated for the impact of resident-physician schedule roster on patient safety outcomes in PICUs, and will allow for examination of a number of secondary outcome measures. ClinicalTrials.gov Identifier: NCT02134847.

An integrated platform for mucin-type O-glycosylation network generation and visualization.

Mucin-type O-glycans have profound effects on the structure and stability of glycoproteins. O-Glycans on the cell surface proteins also modulate the cell's interactions with the surrounding environments and other cells. The synthetic pathway of O-glycans involves a large number of enzymes with diverse substrate specificity. The expression pattern of these enzymes is cell and tissue-specific, thus making the pathway highly diverse. To facilitate pathway analysis in a cell and tissue-specific fashion, we developed an integrated platform of RING (Rule Input Network Generator) and O-GlycoVis. RING uses an English-like reaction language to describe the substrate specificity of enzymes and additional constraints on the formation of the glycan products. Using this information, the RING generates a list of possible glycans, which is used as input into O-Glycovis. O-GlycoVis displays the glycan distribution in the pathway and potential reaction paths leading to each glycan. With the input glycan data, O-GlycoVis also traces all possible reaction paths leading to each glycan and outputs pathway maps with the relative abundance levels of glycans overlaid. O-Glycan profiles from two breast cancer cell lines, MCF7 and T47d, human umbilical vascular endothelium cells, Chinese Hamster Ovary cells were generated based on transcriptional data and compared with experimentally observed O-glycans. This RING-based program allows rules to be added or subtracted for network generation and visualization of networks of O-glycosylation network of different tissues and species.

Cross-sectional analysis of sleep-promoting and wake-promoting drug use on health, fatigue-related error, and near-crashes in police officers.

OBJECTIVES: To examine sleep-promoting and wake-promoting drug use in police officers and associations between their use and health (excessive sleepiness, stress and burnout), performance (fatigue-related errors) and safety (near-crashes) outcomes, both alone and in combination with night-shift work. DESIGN: Cross-sectional survey. SETTING: Police officers from North America completed the survey either online or via paper/pencil at a police station. PARTICIPANTS: 4957 police participated, 3693 online (91.9%, participation rate) and 1264 onsite (cooperation rate 63.1%). MAIN OUTCOME MEASURES: Sleep-promoting and wake-promoting drug use, excessive sleepiness, near-crash motor vehicle crashes, dozing while driving, fatigue errors, stress and burnout. RESULTS: Over the past month, 20% of police officers reported using sleep-promoting drugs and drugs causing sleepiness, while wake-promoting agents were used by 28% of police (5% used wake-promoting drugs, 23% used high levels of caffeine and 4% smoked to stay awake). Use of sleep-promoting drugs was associated with increased near-crashes (OR=1.61; 95% CI 1.21 to 2.13), fatigue-related errors (OR=1.75; 95% CI 1.32 to 2.79), higher stress (OR=1.41; 95% CI 1.10 to 1.82), and higher burnout (OR=1.83; 95% CI 1.40 to 2.38). Wake-promoting drug use, high caffeine and smoking to stay awake were associated with increased odds of a fatigue-related error, stress and burnout (ORs ranging from 1.68 to 2.56). Caffeine consumption was common, and while smoking was not, of those participants who did smoke, one-in-three did so to remain awake. Night-shift work was associated with independent increases in excessive sleepiness, near-crashes and fatigue-related errors. Interactions between night-shift work and wake-promoting drug use were also found for excessive sleepiness. CONCLUSIONS: Police who use sleep-promoting and wake-promoting drugs, especially when working night shifts, are most vulnerable to adverse health, performance and safety outcomes. Future research should examine temporal relationships between shift work, drug use and adverse outcomes, in order to develop optimal alertness management strategies.

Novel use of combination of electromyography and ultrasound to guide quadratus lumborum block after open appendicectomy.

The quadratus lumborum (QL) block facilitates the administration of anaesthesia to the anterior abdominal wall. The use of ultrasound (US) improves the accuracy of the QL block and reduces the risk of adverse events. Electromyography (EMG) in combination with US for muscle plane blocks has not been described previously. We postulated that the addition of EMG-guided needle positioning might assist the execution of this block. This case report describes the first use of combined needle EMG and US to carry out a QL block performed for postoperative analgesia following an open appendicectomy.

Using Contact Forces and Robot Arm Accelerations to Automatically Rate Surgeon Skill at Peg Transfer.

OBJECTIVE: Most trainees begin learning robotic minimally invasive surgery by performing inanimate practice tasks with clinical robots such as the Intuitive Surgical da Vinci. Expert surgeons are commonly asked to evaluate these performances using standardized five-point rating scales, but doing such ratings is time consuming, tedious, and somewhat subjective. This paper presents an automatic skill evaluation system that analyzes only the contact force with the task materials, the broad-bandwidth accelerations of the robotic instruments and camera, and the task completion time. METHODS: We recruited N = 38 participants of varying skill in robotic surgery to perform three trials of peg transfer with a da Vinci Standard robot instrumented with our Smart Task Board. After calibration, three individuals rated these trials on five domains of the Global Evaluative Assessment of Robotic Skill (GEARS) structured assessment tool, providing ground-truth labels for regression and classification machine learning algorithms that predict GEARS scores based on the recorded force, acceleration, and time signals. RESULTS: Both machine learning approaches produced scores on the reserved testing sets that were in good to excellent agreement with the human raters, even when the force information was not considered. Furthermore, regression predicted GEARS scores more accurately and efficiently than classification. CONCLUSION: A surgeon's skill at robotic peg transfer can be reliably rated via regression using features gathered from force, acceleration, and time sensors external to the robot. SIGNIFICANCE: We expect improved trainee learning as a result of providing these automatic skill ratings during inanimate task practice on a surgical robot.

Conservation of the photoperiodic neuroendocrine axis among vertebrates: evidence from the teleost fish, Gasterosteus aculeatus.

Photoperiod, or length of day, has a predictable annual cycle, making it an important cue for the timing of seasonal behavior and development in many organisms. Photoperiod is widely used among temperate and polar animals to regulate the timing of sexual maturation. The proper sensing and interpretation of photoperiod can be tightly tied to an organism's overall fitness. In photoperiodic mammals and birds the thyroid hormone pathway initiates sexual maturation, but the degree to which this pathway is conserved across other vertebrates is not well known. We use the threespine stickleback Gasterosteus aculeatus, as a representative teleost to quantify the photoperiodic response of key genes in the thyroid hormone pathway under controlled laboratory conditions. We find that the photoperiodic responses of the hormones are largely consistent amongst multiple populations, although differences suggest physiological adaptation to various climates. We conclude that the thyroid hormone pathway initiates sexual maturation in response to photoperiod in G. aculeatus, and our results show that more components of this pathway are conserved among mammals, birds, and teleost fish than was previously known. However, additional endocrinology, cell biology and molecular research will be required to define precisely which aspects of the pathway are conserved across vertebrates.