Impact of Exposure to Diesel Exhaust on Inflammation Markers and Proteases in Former Smokers with Chronic Obstructive Pulmonary Disease: A Randomized, Double-blinded, Crossover Study.

Rationale: There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure. Objectives: To document the impact of short-term air pollution exposure on inflammation markers, proteases, and antiproteases in the lower airways of older adults with and without COPD. Methods: Thirty participants (10 ex-smokers with mild to moderate COPD and 20 healthy participants [9 ex-smokers and 11 never-smokers]), with an average age of 60 years, completed this double-blinded, controlled, human crossover exposure study. Each participant was exposed to filtered air (control) and diesel exhaust (DE), in washout-separated 2-hour periods, in a randomly assigned order. Bronchoscopy was performed 24 hours after exposure to collect lavage. Cell counts were performed on blood and airway samples. ELISAs were performed to measure acute inflammatory proteins, matrix proteinases, and antiproteases in the airway and blood samples. Measurements and Main Results: In former smokers with COPD, but not in the other participants, exposure to DE increased serum amyloid A (effect estimate, 1.67; 95% confidence interval [CI], 1.21-2.30; P = 0.04) and matrix metalloproteinase 10 (effect estimate, 2.61; 95% CI, 1.38-4.91; P = 0.04) in BAL. Circulating lymphocytes were increased after DE exposure (0.14 [95% CI, 0.05-0.24] cells × 109/L; P = 0.03), irrespective of COPD status. Conclusions: A controlled human crossover study of DE exposure reveals that former smokers with COPD may be susceptible to an inflammatory response compared with ex-smokers without COPD or never-smoking healthy control participants. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).

Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans.

Outdoor air pollution exposure increases chronic obstructive pulmonary disease (COPD) hospitalisations, and may contribute to COPD development. The mechanisms of harm, and the extent to which at-risk populations are more susceptible are not fully understood. Neutrophils are recruited to the lung following diesel exhaust exposure, a model of traffic-related air pollution (TRAP), but their functional role in this response is unknown. The purpose of this controlled human-exposure crossover study was to assess the effects of acute diesel exhaust exposure on neutrophil function in never-smokers and at-risk populations, with support from additional in vitro studies.18 participants, including never-smokers (n=7), ex-smokers (n=4) and mild-moderate COPD patients (n=7), were exposed to diesel exhaust and filtered air for 2 h on separate occasions, and neutrophil function in blood (0 h and 24 h post-exposure) and bronchoalveolar lavage (24 h post-exposure) was assessed.Compared to filtered air, diesel exhaust exposure reduced the proportion of circulating band cells at 0 h, which was exaggerated in COPD patients. Diesel exhaust exposure increased the amount of neutrophil extracellular traps (NETs) in the lung across participants. COPD patients had increased peripheral neutrophil activation following diesel exhaust exposure. In vitro, suspended diesel exhaust particles increased the amount of NETs measured in isolated neutrophils. We propose NET formation as a possible mechanism through which TRAP exposure affects airway pathophysiology. In addition, COPD patients may be more prone to an activated inflammatory state following exposure.This is the first controlled human TRAP exposure study directly comparing at-risk phenotypes (COPD and ex-smokers) with lower-risk (never-smokers) participants, elucidating the human susceptibility spectrum.

Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study.

Rationale: Diesel exhaust (DE), an established model of traffic-related air pollution, contributes significantly to the global burden of asthma and may augment the effects of allergen inhalation. Newer diesel particulate-filtering technologies may increase NO2 emissions, raising questions regarding their effectiveness in reducing harm from associated engine output.Objectives: To assess the effects of DE and allergen coexposure on lung function, airway responsiveness, and circulating leukocytes, and determine whether DE particle depletion remediates these effects.Methods: In this randomized, double-blind crossover study, 14 allergen-sensitized participants (9 with airway hyperresponsiveness) underwent inhaled allergen challenge after 2-hour exposures to DE, particle-depleted DE (PDDE), or filtered air. The control condition was inhaled saline after filtered air. Blood sampling and spirometry were performed before and up to 48 hours after exposures. Airway responsiveness was evaluated at 24 hours.Measurements and Main Results: PDDE plus allergen coexposure impaired lung function more than DE plus allergen, particularly in those genetically at risk. DE plus allergen and PDDE plus allergen each increased airway responsiveness in normally responsive participants. DE plus allergen increased blood neutrophils and was associated with persistent eosinophilia at 48 hours. DE and PDDE each increased total peripheral leukocyte counts in a manner affected by participant genotypes. Changes in peripheral leukocytes correlated with lung function decline.Conclusions: Coexposure to DE and allergen impaired lung function, which was worse after particle depletion (which increased NO2). Thus, particulates are not necessarily the sole or main culprit responsible for all harmful effects of DE. Policies and technologies aimed at protecting public health should be scrutinized in that regard.Clinical trial registered with www.clinicaltrials.gov (NCT02017431).

Establishing obstetrics-specific metrics and interventions for antimicrobial stewardship.

Background: To describe baseline antimicrobial stewardship (AMS) metrics and apply AMS interventions in an inpatient obstetrical population. Methods: From October 2018 to October 2019, our tertiary-care obstetrical center reviewed components of our AMS program, which included: (1) antimicrobial consumption data, (2) point prevalence surveys (PPS), and (3) prospective audit and feedback. We reviewed institutional data for antimicrobial consumption from the pharmacy database. Detailed point prevalence surveys were conducted for all antimicrobial prescriptions on two predefined dates each month. Daily audits and feedback assessed the appropriateness of all non-protocolized antimicrobials. Results: Our average antimicrobial length of therapy (LOT) was 12 days per 100 patient-days, where erythromycin (2.33), amoxicillin (2.28), and ampicillin (1.81) were the greatest contributors. Point prevalence surveys revealed that 28.8% of obstetrical inpatients were on antimicrobials, of which 11.2% were inappropriate. Protocolized antimicrobials were 62% less likely (p = 0.027) to be inappropriate. From 565 audited prescriptions, 110 (19.5%) resulted in feedback, where 90% of recommendations were accepted and implemented. The most common reasons for interventions include incorrect dosage, recommending a diagnostic test before continuing antimicrobials, and changing antimicrobials based on specific culture and sensitivity. Conclusions: Antimicrobial use in obstetrics is unique compared to general inpatients. We provide a baseline set of metrics for AMS at our obstetrical center intending to lay the groundwork for AMS programming in our discipline. Antimicrobial protocolization, as well as audit and feedback, are feasible interventions to improve antimicrobial prescribing patterns.

Historique: Décrire les mesures de gouvernance antimicrobienne (GAM) fondamentales et utiliser les interventions de GAM dans une population obstétricale hospitalisée. Méthodologie: D'octobre 2018 à octobre 2019, le centre obstétrical de soins tertiaires a révisé les éléments du programme de GAM, qui incluait : 1) les données sur la consommation d'antimicrobiens, 2) les enquêtes de prévalence ponctuelles (EPP) et 3) la vérification et la rétroaction prospectives. Les chercheurs ont examiné les données institutionnelles relatives à la consommation d'antimicrobiens dans la base de données de la pharmacie. Ils ont effectué des enquêtes de prévalence ponctuelles détaillées sur toutes les prescriptions d'antimicrobiens à deux dates déterminées chaque mois. Les vérifications et les rétroactions quotidiennes ont permis d'évaluer la pertinence de tous les antimicrobiens non protocolisés. Résultats: La durée du traitement antimicrobien moyen était de 12 jours sur 100 jours-patients, et l'érythromycine (2,33), l'amoxicilline (2,28) et l'ampicilline (1,81) étaient les plus utilisées. Les enquêtes de prévalence ponctuelles ont révélé que 28,8 % des patientes obstétricales hospitalisées prenaient des antimicrobiens, dont 11,2 % étaient inappropriés. Les antimicrobiens protocolisés étaient 62 % moins susceptibles d'être inappropriés (p = 0,027). Des 565 prescriptions vérifiées, 110 (19,5 %) ont donné lieu à des rétroactions, et 90 % des recommandations ont été acceptées et mises en œuvre. Les principales raisons d'intervenir incluaient une posologie inexacte, la recommandation d'un test diagnostique avant de poursuivre l'antimicrobien, ainsi que le changement d'antimicrobien d'après la culture et sensibilité spécifiques. Conclusions: L'utilisation d'antimicrobiens est unique en obstétrique par rapport aux autres patients hospitalisés. Les chercheurs fournissent la série de mesures de GAM de référence utilisée à leur centre obstétrical pour jeter les bases de la programmation de la GAM dans la discipline. La protocolisation des antimicrobiens, de même que la vérification et la rétroaction, est une intervention faisable pour améliorer les profils de prescription d'antimicrobiens.

Current Recommendations for Perioperative Brain Health: A Scoping Review.

Perioperative complications such as stroke, delirium, and neurocognitive dysfunction are common and responsible for increased morbidity and mortality. Our objective was to characterize and synthesize the contemporary guidelines on perioperative brain health for noncardiac, non-neurologic surgery in a scoping review. We performed a structured search for articles providing recommendations on brain health published between 2016 and 2021 and included the following complications: perioperative stroke and perioperative neurocognitive disorders, the latter of which encompasses postoperative delirium and a spectrum of postoperative cognitive dysfunction. We categorized recommendations by subtopic (stroke, postoperative delirium, postoperative cognitive dysfunction), type (disclosure/ethics/policies, prevention, risk stratification, screening/diagnosis, and management), and pharmacological versus nonpharmacological strategies. We noted country of origin, specialty of the authors, evidence grade (if available), and concordance/discordance between recommendations. Eight publications provided 129 recommendations, originating from the United States (n=5), Europe (n=1), United Kingdom (n=1), and China (n=1). Three publications (37%) applied grading of evidence as follows: Grading of Recommendations, Assessment, Development, and Evaluations (GRADE): A, 30%; B, 36%; C, 30%; D, 4%. We identified 42 instances of concordant recommendations (≥2 publications) on 15 themes, including risk factor identification, risk disclosure, baseline neurocognitive testing, nonpharmacological perioperative neurocognitive disorder prevention, intraoperative monitoring to prevent perioperative neurocognitive disorders, avoidance of benzodiazepines, delaying elective surgery after stroke, and emergency imaging and rapid restoration of cerebral perfusion after perioperative stroke. We identified 19 instances of discordant recommendations on 7 themes, including the use of regional anesthesia and monitoring for perioperative stroke prevention, pharmacological perioperative neurocognitive disorder management, and postoperative stroke screening. We synthesized recommendations for clinical practice and highlighted areas where high-quality evidence is required to inform best practices in perioperative brain health.

Cross-Sectional Analysis of Canadian Anesthesiology Residency Program Website Content.

Background Residency program websites are an important resource widely used by prospective applicants when applying to programs. The objectives of our study were to evaluate the program content available on Canadian anesthesiology residency program websites using established criteria and identify any areas for improvement.  Methods In this cross-sectional study, we evaluated the content available on accredited anesthesiology residency training program websites, between July and August 2021, using 54 criteria provided in the following domains: recruitment; faculty; residents; education and research; clinical work; incentives; wellness; and environment. Website scores were analyzed using descriptive statistics and presented as median (interquartile range), percentage (%), and range. Results We identified 17 programs with publicly available functional websites. Overall, residency programs met a median of 28 (interquartile range: 18-36) website criteria out of 54 (51.9%). Education and research was the highest-scoring domain among residency programs (median 77.8% of criteria met), while resident information and incentives were the lowest (14.3%). Conclusion Canadian anesthesiology residency program websites include information on many domains relevant to prospective applicants, including education and research. However, most websites require improvement and content updates for faculty information, resident information, incentives, wellness, and environment.

Treatment of COVID-19 with convalescent plasma: lessons from past coronavirus outbreaks.

BACKGROUND: There is currently no treatment known to alter the course of coronavirus disease 2019 (COVID-19). Convalescent plasma has been used to treat a number of infections during pandemics, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and now severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). OBJECTIVES: To summarize the existing literature and registered clinical trials on the efficacy and safety of convalescent plasma for treating coronaviruses, and discuss issues of feasibility, and donor and patient selection. SOURCES: A review of articles published in PubMed was performed on 13 July 2020 to summarize the currently available evidence in human studies for convalescent plasma as a treatment for coronaviruses. The World Health Organization International Clinical Trials Registry and clinicaltrials.gov were searched to summarize the currently registered randomized clinical trials for convalescent plasma in COVID-19. CONTENT: There were sixteen COVID-19, four MERS and five SARS reports describing convalescent plasma use in humans. There were two randomized control trials, both of which were for COVID-19 and were terminated early. Most COVID-19 reports described a potential benefit of convalescent plasma on clinical outcomes in severe or critically ill patients with few immediate adverse events. However, there were a number of limitations, including the concurrent use of antivirals, steroids and other treatments, small sample sizes, lack of randomization or control groups, and short follow-up time. Data from SARS and COVID-19 suggest that earlier administration probably yields better outcomes. The ideal candidates for recipients and donors are not known. Still, experience with previous coronaviruses tells us that antibodies in convalescent patients are probably short-lived. Patients who had more severe disease and who are earlier in their course of recovery may be more likely to have adequate titres. Finally, a number of practical challenges were identified. IMPLICATIONS: There is currently no effective treatment for COVID-19, and preliminary trials for convalescent plasma suggest that there may be some benefits. However, research to date is at high risk of bias, and randomized control trials are desperately needed to determine the efficacy and safety of this therapeutic option.

Race, ethnicity, and gender in academic obstetrics and gynecology: 12-year trends.

BACKGROUND: Diversity among healthcare teams enhances team function and improves the quality of patient care and outcomes. Women and racial minorities are historically underrepresented in medicine. However, the representation of gender and racial or ethnic groups in academic obstetrics and gynecology in the United States has not been described in recent years. OBJECTIVE: This study aimed to describe the recent state and trends in gender and racial or ethnic disparities in academic obstetrics and gynecology. STUDY DESIGN: Data from the Association of American Medical Colleges between 2007 and 2018 were analyzed to describe the trends in the representation of women and racial (white, Asian, black) or ethnic (Hispanic) groups. The 12-year trends in representation by academic ranks (all academic physicians, full professor, associate professor, instructor), leadership positions (chairperson), and tenure (not on track for tenure, on track for tenure, or tenured) were depicted. The 12-year trends were assessed using linear regression to determine whether the slope depicting the change in representation of each group from 2007 to 2018 was significantly nonzero. In addition, average representation of each group across the 12-year period was compared using a Student t test (for gender) or analysis of variance (for race and ethnicity). RESULTS: In 2018, there were 152 institutions and 6302 academic physicians included in the data set. On average across the 12-year period, academic physicians in obstetrics and gynecology were 43% male, 57% female, 68% white, 12% Asian, 8% black, and 5% Hispanic. Across the 12-year period, there was an increase in the total number of physicians from 4755 to 6302 (+166 per year; 95% confidence interval, 146-186; P<.0001), a 15% increase in the proportion of women (+1.38% per year; 95% confidence interval, 1.08%-1.68%; P<.0001), and an increase in the proportion of physicians from racial minorities (Asian, +0.11% per year; 95% confidence interval, 0.08-0.15; P<.0001; black, +0.07% per year; 95% confidence interval, 0.04-0.09; P=.0002; Hispanic, +0.06% per year; 95% confidence interval, 0.02-0.1; P=.0039). There was a greater proportion of white physicians in higher academic ranks (eg, full professor), leadership positions (eg, chairperson), and tenure than the proportion of white physicians overall, whereas the opposite was true for black and Hispanic physicians. Although women now make up 64% of all academic physicians in obstetrics and gynecology, there remains a far higher proportion of males in leadership positions (chairperson) and higher academic ranks (full professor). Similarly, a greater proportion of males were tenured than females. CONCLUSION: Across the 12-year period, the representation of women and racial minorities has increased in academic obstetrics and gynecology in the United States. There is now a predominance of women, but there remains a trend for a predominance of white and male physicians in higher academic ranks, leadership positions, and tenure. It will be important to assess how these groups are represented in the coming years as the changing demographics of incoming cohorts progress through their careers to more senior positions. Promoting diversity in medical schools, leadership positions, and higher academic ranks may be an important area of focus.

Whole-body net protein balance plateaus in response to increasing protein intakes during post-exercise recovery in adults and adolescents.

BACKGROUND: Muscle protein synthesis and muscle net balance plateau after moderate protein ingestion in adults. However, it has been suggested that there is no practical limit to the anabolic response of whole-body net balance to dietary protein. Moreover, limited research has addressed the anabolic response to dietary protein in adolescents. The present study determined whether whole-body net balance plateaued in response to increasing protein intakes during post-exercise recovery and whether there were age- and/or sex-related dimorphisms in the anabolic response. METHODS: Thirteen adults [7 males (M), 6 females (F)] and 14 adolescents [7 males (AM), 7 females (AF) within ~ 0.4 y from peak height velocity] performed ~ 1 h variable intensity exercise (i.e., Loughborough Intermittent Shuttle Test) prior to ingesting hourly mixed meals that provided a variable amount of protein (0.02-0.25 g·kg- 1·h- 1) as crystalline amino acids modeled after egg protein. Steady-state protein kinetics were modeled noninvasively with oral L-[1-13C]phenylalanine. Breath and urine samples were taken at plateau to determine phenylalanine oxidation and flux (estimate of protein breakdown), respectively. Whole-body net balance was determined by the difference between protein synthesis (flux - oxidation) and protein breakdown. Total amino acid oxidation was estimated from the ratio of urinary urea/creatinine. RESULTS: Mixed model biphasic linear regression explained a greater proportion of net balance variance than linear regression (all, r 2 ≥ 0.56; P < 0.01), indicating an anabolic plateau. Net balance was maximized at ~ 0.15, 0.12, 0.12, and 0.11 g protein·kg- 1·h- 1 in M, F, AM, and AF, respectively. When collapsed across age, the y-intercept (net balance at very low protein intake) was greater (overlapping CI did not contain zero) in adolescents vs. adults. Urea/creatinine excretion increased linearly (all, r ≥ 0.76; P < 0.01) across the range of protein intakes. At plateau, net balance was greater (P < 0.05) in AM vs. M. CONCLUSIONS: Our data suggest there is a practical limit to the anabolic response to protein ingestion within a mixed meal and that higher intakes lead to deamination and oxidation of excess amino acids. Consistent with a need to support lean mass growth, adolescents appear to have greater anabolic sensitivity and a greater capacity to assimilate dietary amino acids than adults.

Variable-Intensity Simulated Team-Sport Exercise Increases Daily Protein Requirements in Active Males.

Protein requirements are generally increased in strength and endurance trained athletes relative to their sedentary peers. However, less is known about the daily requirement for this important macronutrient in individuals performing variable intensity, stop-and-go type exercise that is typical for team sport athletes. The objective of the present study was to determine protein requirements in active, trained adult males performing a simulated soccer match using the minimally invasive indicator amino acid oxidation (IAAO) method. After 2 days of controlled diet (1.2 g⋅kg-1⋅day-1 protein), seven trained males (23 ± 1 years; 177.5 ± 6.7 cm; 82.3 ± 6.1 kg; 13.5% ± 4.7% body fat; 52.3 ± 5.9 ml O2⋅kg-1⋅min-1; mean ± SD) performed an acute bout of variable intensity exercise in the form of a modified Loughborough Intermittent Shuttle Test (4 × 15 min of exercise over 75 min). Immediately after exercise, hourly meals were consumed providing a variable amount of protein (0.2-2.6 g⋅kg-1⋅day-1) and sufficient energy and carbohydrate (6 g⋅kg-1⋅day-1). Protein was provided as a crystalline amino acids modeled after egg protein with the exception of phenylalanine and tyrosine, which were provided in excess to ensure the metabolic partitioning of the indicator amino acid (i.e., [1-13C]phenylalanine included within the phenylalanine intake) was directed toward oxidation when protein intake was limiting. Whole body phenylalanine flux and 13CO2 excretion (F13CO2) were determined at metabolic and isotopic steady state from urine and breath samples, respectively. Biphasic linear regression analysis was performed on F13CO2 to determine the estimated average requirement (EAR) for protein with a safe intake defined as the upper 95% confidence interval. Phenylalanine flux was not impacted by protein intake (P = 0.45). Bi-phase linear regression (R2 = 0.64) of F13CO2 resulted in an EAR and safe intake of 1.20 and 1.40 g⋅kg-1⋅day-1, respectively. Variable intensity exercise increases daily protein requirements compared to the safe intake determined by nitrogen balance (0.83 g⋅kg-1⋅day-1) and IAAO (1.24 g⋅kg-1⋅day-1) but is within the range (i.e., 1.2-2.0 g⋅kg-1⋅day-1) of current consensus statements on general recommendations for athletes. CLINICAL TRIAL REGISTRATION: This trial was registered June 18, 2015 at http://clinicaltrials.gov as NCT02478814.

Increased Protein Requirements in Female Athletes after Variable-Intensity Exercise.

PURPOSE: Protein requirements are primarily studied in the context of resistance or endurance exercise with little research devoted to variable-intensity intermittent exercise characteristic of many team sports. Further, female populations are underrepresented in dietary sports science studies. We aimed to determine a dietary protein requirement in active females performing variable-intensity intermittent exercise using the indicator amino acid oxidation (IAAO) method. We hypothesized that these requirements would be greater than current IAAO-derived estimates in nonactive adult males. METHODS: Six females (21.2 ± 0.8 yr, 68.8 ± 4.1 kg, 47.1 ± 1.2 mL O2·kg·min; mean ± SE) completed five to seven metabolic trials during the luteal phase of the menstrual cycle. Participants performed a modified Loughborough Intermittent Shuttle Test before consuming eight hourly mixed meals providing the test protein intake (0.2-2.66 g·kg·d), 6 g·kg·d CHO and sufficient energy for resting and exercise-induced energy expenditure. Protein was provided as crystalline amino acid modeling egg protein with [C]phenylalanine as the indicator amino acid. Phenylalanine turnover (Q) was determined from urinary [C]phenylalanine enrichment. Breath CO2 excretion (FCO2) was analyzed using mixed effects biphase linear regression with the breakpoint and upper 95% confidence interval approximating the estimated average requirement and recommended dietary allowance, respectively. RESULTS: Protein intake had no effect on Q (68.7 ± 7.3 µmol·kg·h; mean ± SE). FCO2 displayed a robust biphase response (R = 0.66) with an estimated average requirement of 1.41 g·kg·d and recommended dietary allowance of 1.71 g·kg·d. CONCLUSIONS: The protein requirement estimate of 1.41 and 1.71 g·kg·d for females performing variable-intensity intermittent exercise is greater than the IAAO-derived estimates of adult males (0.93 and 1.2 g·kg·d) and at the upper range of the American College of Sports Medicine athlete recommendations (1.2-2.0 g·kg·d).