Anesthesia environmental sustainability programs-a survey of Canadian department chiefs and residency program directors.

INTRODUCTION: Anesthesia-related activities contribute to operating room waste impacting climate change. The aim of this study was to ascertain 1) the current existence and scope of department and education programs concerned with anesthesia "green" practice; and 2) perceived barriers to environmental sustainability efforts among Canadian anesthesia department chiefs and residency program directors. METHODS: Association of Canadian University Departments of Anesthesia-affiliated anesthesiology department chiefs (n = 113) were invited to complete an online survey ascertaining current efforts in, and barriers to, environmentally sustainable anesthesia practice. Similarly, Canadian anesthesiology residency program directors (n = 17) were invited to complete an online survey delineating current educational programs on environmental sustainability and identifying interest in, and barriers to, developing a Canada-wide curriculum. RESULTS: The response rates for department chiefs and program directors were 23% (26/113) and 41% (7/17), respectively. Department chiefs indicated that their departments participate in sustainability efforts such as donating medical equipment (65%) and recycling (58%). Despite interest in environmental sustainability, department chiefs identified inadequate funding (72%), lack of a mandate (64%), and inadequate knowledge (60%) as barriers to implementing environmentally sustainable practices. Only 29% of responding Canadian anesthesiology programs include environmental sustainability in their curriculum. Responding residency program directors believe residents would benefit from more teaching on the topic (86%) but identified barriers including a lack of faculty expertise (100%) and time constraints (71%). Respondents (71%) also indicated an interest in developing a Canadian curriculum on the topic. CONCLUSION: Our results highlight current attitudes, gaps, and barriers to environmentally sustainable anesthesiology practice among departmental and educational leadership. Furthermore, this study identifies potential opportunities to develop cross-Canada collaborative educational programs in this field.

RéSUMé: INTRODUCTION: Les activités liées à l'anesthésie contribuent aux déchets de salle d'opération qui ont un impact sur les changements climatiques. L'objectif de cette étude était d'établir 1) l'existence et la portée des programmes départementaux et de formation s'intéressant à une pratique écoresponsable de l'anesthésie; et 2) les obstacles perçus aux efforts en matière de durabilité environnementale parmi les chefs de départements et les directeurs de programmes de résidence en anesthésie canadiens. MéTHODE: Les chefs des départements d'anesthésiologie affiliés à l'Association canadienne universitaire des départements d'anesthésie (ACUDA) (n = 113) ont été invités à remplir un sondage en ligne afin de déterminer les efforts actuels et les obstacles à une pratique durable de l'anesthésie. Les directeurs de programmes de résidence en anesthésiologie canadiens (n = 17) ont également été invités à remplir un sondage en ligne décrivant les programmes de formation actuels portant sur la durabilité environnementale et identifiant l'intérêt pour et les obstacles à la création d'un cursus s'appliquant à tout le Canada. RéSULTATS: Les taux de réponse des chefs de département et des directeurs de programme étaient de 23 % (26/113) et 41 % (7/17), respectivement. Les chefs de département ont indiqué que leurs départements prenaient part aux efforts de durabilité en faisant don des équipements médicaux (65 %) et en recyclant (58 %). Malgré un intérêt pour la durabilité environnementale, les chefs de département ont fait mention d'un financement inadapté (72 %), de l'absence de mandat (64 %), et d'un manque de connaissances (60 %) en tant qu'obstacles à la mise en place de pratiques durables. Seuls 29 % des programmes d'anesthésiologie canadiens ayant répondu comportaient un volet sur la durabilité environnementale dans leur programme. Les directeurs de programmes de résidence ayant répondu étaient d'avis que les résidents bénéficieraient d'une augmentation de l'enseignement à ce sujet (86 %) mais ont identifié divers obstacles, notamment un manque d'expertise du corps enseignant (100 %) et des contraintes de temps (71 %). Les répondants (71 %) ont également indiqué leur intérêt pour la création d'un cursus canadien à ce sujet. CONCLUSION: Nos résultats résument les attitudes, écueils et obstacles actuels à une pratique durable de l'anesthésiologie parmi les directions des départements et des programmes de formation. En outre, cette étude identifie des occasions potentielles de création de programmes éducatifs collaboratifs pancanadiens dans ce domaine.

Hospital admission on weekends for patients who have surgery and 30-day mortality in Ontario, Canada: A matched cohort study.

BACKGROUND: Healthcare interventions on weekends have been associated with increased mortality and adverse clinical outcomes, but these findings are inconsistent. We hypothesized that patients admitted to hospital on weekends who have surgery have an increased risk of death compared with patients who are admitted and have surgery on weekdays. METHODS AND FINDINGS: This matched cohort study included 318,202 adult patients from Ontario health administrative and demographic databases, admitted to acute care hospitals from 1 January 2005 to 31 December 2015. A total of 159,101 patients who were admitted on weekends and underwent noncardiac surgery were classified by day of surgery (weekend versus weekday) and matched 1:1 to patients who both were admitted and had surgery on a weekday (Tuesday to Thursday); matching was based on age (in years), anesthesia basic unit value for the surgical procedure, median neighborhood household income quintile, resource utilization band (a ranking system of overall morbidity), rurality of home location, year of admission, and urgency of admission. Of weekend admissions, 16.2% (25,872) were elective and 53.9% (85,744) had surgery on the weekend of admission. The primary outcome was all-cause mortality within 30 days of the date of hospital admission. The 30-day all-cause mortality for patients admitted on weekends who had noncardiac surgery was 2.6% (4,211/159,101) versus 2.5% (3,901/159,101) for those who were admitted and had surgery on weekdays (adjusted odds ratio [OR] 1.05; 95% CI 1.00 to 1.11; P = 0.03). However, there was significant heterogeneity in the increased odds of death according to the urgency of admission and when surgery was performed (weekend versus weekday). For urgent admissions on weekends (n = 133,229), there was no significant increase in odds of mortality when surgery was performed on the weekend (adjusted OR 1.02; 95% CI 0.95 to 1.09; P = 0.7) or on a subsequent weekday (adjusted OR 1.05; 95% CI 0.98 to 1.12; P = 0.2) compared to urgent admissions on weekdays. Elective admissions on weekends (n = 25,782) had increased risk of death both when surgery was performed on the weekend (adjusted OR 3.30; 95% CI 1.98 to 5.49; P < 0.001) and when surgery was performed on a subsequent weekday (adjusted OR 2.70; 95% CI 1.81 to 4.03; P < 0.001). The main limitations of this study were the lack of data regarding reason for admission and cause of increased time interval from admission to surgery for some cases, the small number of deaths in some subgroups (i.e., elective surgery), and the possibility of residual unmeasured confounding from increased illness severity for weekend admissions. CONCLUSIONS: When patients have surgery during their hospitalization, admission on weekends in Ontario, Canada, was associated with a small but significant proportional increase in 30-day all-cause mortality, but there was significant heterogeneity in outcomes depending on the urgency of admission and when surgery was performed. An increased risk of death was found only for elective admissions on weekends; whether this is a function of patient-level factors or represents a true weekend effect needs to be further elucidated. These findings have potential implications for resource allocation in hospitals and the redistribution of elective surgery to weekends.

A national survey on attitudes and barriers on recycling and environmental sustainability efforts among Canadian anesthesiologists: an opportunity for knowledge translation.

BACKGROUND: Anesthesia-related activities produce 25% of all operating room (OR) waste and contribute to environmental pollution and climate change. The aim of this study was to document Canadian anesthesiologists' current practice, attitudes towards, and perceived barriers regarding recycling of OR waste and environmental sustainability efforts. METHODS: With Research Ethics Board approval, members of the Canadian Anesthesiologists' Society (CAS) completed an online survey consisting of 25 questions assessing current environmentally sustainable practices in anesthesiology and gaps, barriers, and interest in gaining further knowledge on this topic. RESULTS: Four hundred and twenty-six of 2,695 (16%) CAS members responded to the questionnaire. Despite a willingness to recycle at work among most anesthesiologists (393/403, 97.5%), only 122/403 (30.2%) did so. Other sustainability efforts in Canadian ORs included donating unused medical equipment and supplies to medical missions (198/400, 49.5%) and evening shut-off of anesthesia machines and other OR equipment (185/400, 46.3%). Reported barriers to recycling in the OR included a lack of support from hospital/OR leadership (254/400, 63.5%) and inadequate information/education (251/400, 62.8%). Only 122/389 (31.4%) of respondents were aware of any efforts to expand sustainability programs at their institutions but 273/395 (69.1%) of respondents indicated an interest in obtaining further education on the topic. CONCLUSION: Canadian anesthesiologists appear ready to incorporate environmental sustainability in their practice but indicate that significant barriers exist. Our study highlights the need for further educational programs and implementation strategies.

RéSUMé: CONTEXTE: Les activités liées à l'anesthésie produisent 25 % de tous les déchets en salle d'opération et contribuent à la pollution de l'environnement et au changement climatique. Le but de cette étude était de documenter les pratiques actuelles des anesthésiologistes canadiens, leurs attitudes envers le recyclage des déchets de salle d'opération et les efforts pour la protection de l'environnement, ainsi que les obstacles perçus comme s'y opposant. MéTHODES: Après approbation d'un Comité d'éthique de la recherche, les membres de la Société canadienne des anesthésiologistes (SCA) ont pu remplir une enquête en ligne comportant 25 questions évaluant les pratiques actuelles en anesthésiologie pour un environnement durable ses obstacles, ses lacunes, ainsi que l'intérêt à en savoir plus sur ce sujet. RéSULTATS: Quatre cent vingt-six des 2695 membres (16 %) de la SCA ont répondu au questionnaire. Malgré un désir de recyclage dans le cadre du travail chez la plupart des anesthésiologistes (393/403, 97,5 %), seulement 122/403 (30,2 %) le faisaient. D'autres efforts des salles d'opération canadiennes en faveur de la durabilité incluaient le don de l'équipement médical et des fournitures non utilisés à des missions médicales (198/400, 49,5 %) et la fermeture des appareils d'anesthésie et des autres équipements de la salle d'opération le soir (185/400, 46,3 %). Les obstacles au recyclage en salle d'opération qui ont été mentionnés incluaient une absence de soutien de la part du leadership de l'hôpital/de la salle d'opération (254/400, 63,5 %) et une information/éducation insuffisante sur le sujet (251/400, 62,8 %). Seulement 122 des 389 répondants (31,4 %) étaient au courant d'efforts d'extension des programmes en faveur de l'environnement, mais 273/395 (69,1 %) répondants ont manifesté de l'intérêt à obtenir plus de formation sur le sujet. CONCLUSION: Les anesthésiologistes canadiens semblent prêts à incorporer la protection de l'environnement dans leurs pratiques, mais indiquent qu'il existe des obstacles significatifs. Notre étude souligne le besoin de poursuivre les programmes éducatifs et les stratégies de mise en œuvre.

Incidence of non-physiologically complex surgical procedures performed in children: an Ontario population-based study of health administrative data.

PURPOSE: Quantification of surgical procedures undertaken by hospitals is necessary for informing resource allocation and modelling healthcare services. Our objective was to quantify the incidence, similarity, and diversity of non-physiologically complex surgical procedures performed at pediatric specialist hospitals and other hospitals performing pediatric surgery. METHODS: We conducted a population-based cohort study of children aged 28 days to 18 yr who underwent surgery in the province of Ontario from 2007 to 2015 using healthcare administrative databases. We estimated the incidence of non-physiologically complex procedures (i.e., ≤ 7 basic units in the 2015 Ontario Health Insurance Plan Schedule of Benefits) performed in pediatric specialist hospitals and other hospitals performing pediatric surgery. We used Yue and Clayton's index and the effective number of common procedures (1/Herfindahl index) to quantify the similarity and diversity of pediatric surgical procedures performed in these hospital types. RESULTS: Overall, 830,830 pediatric surgical procedures were performed in 158 Ontario hospitals during the eight-year study period. Most surgical procedures performed at hospitals performing pediatric surgery were non-physiologically complex (vs 50%, P < 0.001). The incidence of non-physiologically complex procedures increased progressively each year at pediatric specialist hospitals and was associated with a reciprocal decline among the other hospitals. Comparing pediatric specialist hospitals with the other hospitals, the mean similarity index for non-physiologically complex procedures was less than moderate (0.52; 95% confidence interval [CI], 0.51 to 0.54). The mean effective number of common non-physiologically complex procedures (i.e., the diversity) among the pediatric specialist hospitals was greater than at the other 154 hospitals performing pediatric surgery (65.3 vs 21.8 procedures, respectively; mean difference, 43.5; 95% CI, 42.2 to 44.8; P < 0.001). CONCLUSIONS: Non-physiologically complex procedures have progressively migrated to pediatric specialist hospitals from other hospitals in Ontario. Specialty pediatric hospitals are principally dissimilar from other hospitals performing pediatric surgery based not on physiological complexity, but on their diversity. These findings suggest that some types of surgical procedures may be redistributed from specialist pediatric hospitals to other hospitals performing pediatric surgery. TRIAL REGISTRATION: www.clinicaltrials.gov , number NCT03144544. Registered 2 May 2016.

New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures.

We report useful new lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades. A strategic nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C-C or C-X bond-forming events via resulting chiral enamide intermediates or imine products. The mechanism of the amino-Cope rearrangement was explored with density functional theory. A stepwise dissociation-recombination mechanism was found to be favored. The stereochemistry of the chiral auxiliary determines the stereochemistry of the Cope product by influencing the orientation of the lithium dienolate and sulfinylimine fragments in the recombination step. These robust asymmetric anion-accelerated amino-Cope enabled cascades open the door for rapid and predictable assembly of complex chiral acyclic and cyclic nitrogen-containing motifs in one pot.

Dexamethasone as an adjuvant to peripheral nerve block.

BACKGROUND: Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone. OBJECTIVES: To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events. AUTHORS' CONCLUSIONS: Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.

L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats.

BACKGROUND: The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg-1 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. METHODS: In the first of two experiments, L-carnitine 100 mg·kg-1 iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg-1·min-1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg-1 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg-1, L-carnitine 100 mg·kg-1, 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. RESULTS: In the first study, L-carnitine 100 mg·kg-1 increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). CONCLUSION: These findings suggest that acute administration of L-carnitine 100 mg·kg-1 decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.

The efficacy and durability of the Venous Window Needle Guide implanted on uncannulatable arteriovenous fistulas.

BACKGROUND: The Venous Window Needle Guide (VWING; Vital Access Corp, Salt Lake City, Utah) is a surgically implanted titanium device designed to facilitate cannulation of uncannulatable dialysis access arteriovenous fistulas (AVFs) because of excessive depth, aneurysm formation, or tortuosity but that exhibit sufficient flow volume to support hemodialysis. We report the 18-month fistula patency, functionality, and complications of the use of the VWING device. METHODS: This retrospective study examined AVF patency, VWING functionality, interventions, and device infections at 18 months after VWING implantation. The study population comprised the eligible patients enrolled in the VWING Salvage of AV Fistula (SAVE) trial. RESULTS: Fifty-four patients were originally enrolled in the SAVE trial, and 35 were enrolled in the follow-up study. At 18 months, when considering surgical or percutaneous interventions at the VWING site(s) only, the primary AVF patency rate was 78%. Interventions elsewhere on the AVF, outside the boundaries of the VWING, resulted in a primary patency rate of 38%. The VWING accounted for 13% loss of AVF primary patency compared with 53% loss from the remaining AVFs. The overall AVF assisted primary patency rate was 91%, and the primary patency rate was 21%. VWING secondary functionality, the continued ability to access the fistula through the VWING using a constant site cannulation technique, was 65%. During the 12 months after the SAVE Study 80% of patients did not require the use of a central venous catheter. Eleven VWING devices were removed from eight patients, all but one for cannulation difficulties. One device was removed during the SAVE trial because of infection. No device or systemic infection was identified in the ensuing 12 months, for an overall systemic infection rate of 0.014 per device-year. An intervention rate of 0.32 per device-year was required to maintain device functionality during the 18-month follow-up period. CONCLUSIONS: Implantation of the VWING device is a safe and effective means of establishing hemodialysis access in an otherwise functional but uncannulatable AVF. The device infection rate is acceptably low.

A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry.

BACKGROUND: It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. METHODS: The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children's developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. RESULTS: Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. CONCLUSIONS: Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

Effect of surgical safety checklists on pediatric surgical complications in Ontario.

BACKGROUND: In health care, most preventable adverse events occur in the operating room. Surgical safety checklists have become a standard of care for safe operating room practice, but there is conflicting evidence for the effectiveness of checklists to improve perioperative outcomes in some populations. Our objective was to determine whether surgical safety checklists are associated with a reduction in the proportion of children who had perioperative complications. METHODS: We conducted a retrospective cohort study using administrative health care databases housed at the Institute for Clinical Evaluative Sciences to compare the risk of perioperative complications in children undergoing common types of surgery before and after the mandated implementation of surgical safety checklists in 116 acute care hospitals in Ontario. The primary outcome was a composite outcome of 30-day all-cause mortality and perioperative complications. RESULTS: We identified 14 458 and 14 314 surgical procedures in pre- and postchecklist groups, respectively. The proportion of children who had perioperative complications was 4.08% (95% confidence interval [CI] 3.76%-4.40%) before the implementation of the checklist and 4.12% (95% CI 3.80%-4.45%) after implementation. After we adjusted for confounding factors, we found no significant difference in the odds of perioperative complications after the introduction of surgical safety checklists (adjusted odds ratio 1.01, 95% CI 0.90-1.14, p = 0.9). INTERPRETATION: The implementation of surgical safety checklists for pediatric surgery in Ontario was not associated with a reduction in the proportion of children who had perioperative complications. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02419053.

Do clinicians understand the size of treatment effects? A randomized survey across 8 countries.

BACKGROUND: Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences - from trivial to large - can, however, be challenging. We investigated clinicians' understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference). METHODS: We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paper-based, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants' understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1). RESULTS: Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful. INTERPRETATION: None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.

Patient-Controlled Analgesia Plus Background Opioid Infusion for Postoperative Pain in Children: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Bolus administration of opioids via a patient-controlled analgesia (PCA) device is widely used in the postoperative pediatric population. PCA devices have been shown to provide superior analgesia and greater patient satisfaction compared with intermittent administration. Studies comparing the efficacy of PCA with and without a background infusion for postoperative analgesia in children vary considerably in terms of dosing and methodologic quality, making it difficult for practitioners to derive clinically useful information. The purpose of this meta-analysis was to assess whether the addition of a background infusion to PCA bolus administration of an opioid analgesic is more effective (defined as lower pain scores) than PCA bolus alone in the postoperative population specific to children. METHODS: We searched Medline, Embase, and CENTRAL from inception to January 2015 for registered and ongoing trials included in the meta-Register of Controlled Trials and ClinicalTrials.gov, and reference lists of review articles and included articles. Study selection was randomized controlled studies comparing PCA bolus with PCA bolus plus background infusion for postoperative analgesia in children aged 0 to 18 years and adolescents aged 13 to 21 years undergoing any form of surgery that used patient-reported pain scores as an outcome measure. Two reviewers independently extracted data on patient and study characteristics, interventions, and outcomes from included studies using standardized data extraction forms. Seven trials met our eligibility criteria. Data were analyzed using Review Manager version 5.3. Meta-analyses were performed for outcomes that were defined similarly and reported in 2 or more studies, including patient-reported pain scores, nausea and/or vomiting, sedation, and opioid consumption. We independently assessed the risk of bias for each outcome and the certainty in the estimates of effect for critically important outcomes (pain scores, nausea and/or vomiting, excessive sedation) using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Subgroup analyses based on dose of background infusion (high versus low dose) and risk of bias (low versus high/unclear) were performed. RESULTS: There were no significant differences found with respect to pain scores 12 and 24 hours after surgery, opioid consumption, or risk of adverse events with the addition of a background opioid infusion to PCA opioid bolus doses. The quality of the evidence was deemed to be low to very low. CONCLUSIONS: There was no significant difference in outcomes with the addition of an opioid background infusion to PCA bolus doses of opioid. Further high-quality studies are required.

Perspectives on Canadian core fellowship training in pediatric anesthesia: a survey of graduate fellows.

BACKGROUND: Educators in anesthesia have an obligation to ensure that fellowship programs are training anesthesiologists to meet the highest standards of performance in clinical and academic practice. The objective of this survey was to characterize the perspectives of graduates of Canadian core fellowship programs in pediatric anesthesia (during a ten-year period starting in 2003) on the adequacies and inadequacies of fellowship training. METHODS: We conducted an electronic survey of graduates from eight departments of pediatric anesthesia in Canada who completed one-year core fellowship training in pediatric anesthesia from 2003 to 2013. A novel survey design was implemented, and the content and structure of the design were tested before distribution. Data were collected on respondents' demographics, details of training and practice settings, perceived self-efficacy in subspecialty practices, research experience, and perspectives on one-year core fellowship training in pediatric anesthesia. Descriptive statistics and 95% confidence intervals were determined. RESULTS: The survey was sent to 132 anesthesiologists who completed core fellowship training in pediatric anesthesia in Canada. Sixty-five (49%) completed and eligible surveys were received. Most of the anesthesiologists surveyed perceived that 12 months of core fellowship training are sufficient to acquire the knowledge and critical skills needed to practice pediatric anesthesia. Subspecialty areas most frequently perceived to require improved training included pediatric cardiac anesthesia, chronic pain medicine, and regional anesthesia. CONCLUSIONS: This survey reports perceived deficiencies in domains of pediatric anesthesia fellowship training. These findings should help guide the future development of core and advanced fellowship training programs in pediatric anesthesia.

A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.

PURPOSE: Discharge criteria based on physiological scoring systems can be used in the postanesthesia care unit (PACU) to fast-track patients after ambulatory surgery; however, studies comparing physiological scoring systems with traditional time-based discharge criteria are lacking. The purpose of this study was to compare PACU discharge readiness times using physiological vs time-based discharge criteria in pediatric ambulatory surgical patients. METHODS: We recorded physiological observations from consecutive American Society of Anesthesiologists physical status I-III patients aged 1-18 yr who were admitted to the PACU after undergoing ambulatory surgery in a tertiary academic pediatric hospital. The physiological score was a combination of the Aldrete and Chung systems. Scores were recorded every 15 min starting upon arrival in the PACU. Patients were considered fit for discharge once they attained a score ≥12 (maximum score, 14), provided no score was zero, with the time to achieve a score ≥12 defining the criteria-based discharge (CBD) time. Patients were discharged from the PACU when both the CBD and the existing time-based discharge (TBD) criteria were met. The CBD and TBD data were compared using Kaplan-Meier and log-rank analysis. RESULTS: Observations from 506 children are presented. Median (interquartile range [IQR]) age was 5.5 [2.8-9.9] yr. Median [IQR] CBD and TBD PACU discharge readiness times were 30 [15-45] min and 60 [45-60] min, respectively. Analysis of Kaplan-Meier curves indicated a significant difference in discharge times using the different criteria (hazard ratio, 5.43; 95% confidence interval, 4.51 to 6.53; P < 0.001). All patients were discharged home without incident. CONCLUSIONS: This prospective study suggests that discharge decisions based on physiological criteria have the potential for significantly speeding the transit of children through the PACU, thereby enhancing PACU efficiency and resource utilization.

Erratum to: A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.

Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0428-6. In the published version, the first phrase of the introduction was incorrect and should read as follows: Since the inception of the postanesthesia care unit (PACU) in 1923, the question of when it is safe to discharge a patient has remained contentious. The publisher apologizes most sincerely for this typesetting error.

Nuclear cytoplasmic trafficking of proteins is a major response of human fibroblasts to oxidative stress.

We have used a subcellular spatial razor approach based on LC-MS/MS-based proteomics with SILAC isotope labeling to determine changes in protein abundances in the nuclear and cytoplasmic compartments of human IMR90 fibroblasts subjected to mild oxidative stress. We show that response to mild tert-butyl hydrogen peroxide treatment includes redistribution between the nucleus and cytoplasm of numerous proteins not previously associated with oxidative stress. The 121 proteins with the most significant changes encompass proteins with known functions in a wide variety of subcellular locations and of cellular functional processes (transcription, signal transduction, autophagy, iron metabolism, TCA cycle, ATP synthesis) and are consistent with functional networks that are spatially dispersed across the cell. Both nuclear respiratory factor 2 and the proline regulatory axis appear to contribute to the cellular metabolic response. Proteins involved in iron metabolism or with iron/heme as a cofactor as well as mitochondrial proteins are prominent in the response. Evidence suggesting that nuclear import/export and vesicle-mediated protein transport contribute to the cellular response was obtained. We suggest that measurements of global changes in total cellular protein abundances need to be complemented with measurements of the dynamic subcellular spatial redistribution of proteins to obtain comprehensive pictures of cellular function.

Systematic nucleo-cytoplasmic trafficking of proteins following exposure of MCF7 breast cancer cells to estradiol.

We have used a proteomics subcellular spatial razor approach to look at changes in total protein abundance and in protein distribution between the nucleus and cytoplasm following exposure of MCF7 breast cancer cells to estradiol. The dominant response of MCF7 cells to estrogen stimulation involves dynamic changes in protein subcellular spatial distribution rather than changes in total protein abundance. Of the 3604 quantitatively monitored proteins, only about 2% show substantial changes in total abundance (>2-fold), whereas about 20% of the proteins show substantial changes in local abundance and/or redistribution of their subcellular location, with up to 16-fold changes in their local concentration in the nucleus or the cytoplasm. We propose that dynamic redistribution of the subcellular location of multiple proteins in response to stimuli is a fundamental characteristic of cells and suggest that perturbation of cellular spatial control may be an important feature of cancer.

Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury.

Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFß1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFß1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.

The proteome of Toll-like receptor 3-stimulated human immortalized fibroblasts: implications for susceptibility to herpes simplex virus encephalitis.

BACKGROUND: Inborn errors in Toll-like receptor 3 (TLR3)-IFN type I and III pathways have been implicated in susceptibility to herpes simplex virus encephalitis (HSE) in children, but most patients studied do not carry mutations in any of the genes presently associated with HSE susceptibility. Moreover, many patients do not display any TLR3-IFN-related fibroblastic phenotype. OBJECTIVE: To study other signaling pathways downstream of TLR3 and/or other independent pathways that may contribute to HSE susceptibility. METHODS: We used the stable isotope labeling of amino acids in cell culture proteomics methodology to measure changes in the human immortalized fibroblast proteome after TLR3 activation. RESULTS: Cells from healthy controls were compared with cells from a patient with a known genetic etiology of HSE (UNC-93B-/-) and also to cells from an HSE patient with an unknown gene defect. Consistent with known variation in susceptibility of individuals to viral infections, substantial variation in the response level of different healthy controls was observed, but common functional networks could be identified, including upregulation of superoxide dismutase 2. The 2 patients with HSE studied show clear differences in functional response networks when compared with healthy controls and also when compared with each other. CONCLUSIONS: The present study delineates a number of novel proteins, TLR3-related pathways, and cellular phenotypes that may help elucidate the genetic basis of childhood HSE. Furthermore, our results reveal superoxide dismutase 2 as a potential therapeutic target for amelioration of the neurologic sequelae caused by HSE.