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1. Interprofessional Staffing Pattern Clusters in U.S. ICUs

Author: Hayley B. Gershengorn, MD, FCCM, ATSF, Deena Kelly Costa, PhD, RN, FAAN, Allan Garland, MD, MA, Danny Lizano, MSHS, PA-C, FCCM, and Hannah Wunsch, MD, MSc, FCCM
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. To identify interprofessional staffing pattern clusters used in U.S. ICUs. DESIGN:. Latent class analysis. SETTING AND PARTICIPANTS:. Adult U.S. ICUs. PATIENTS:. None. INTERVENTIONS:. None. ANALYSIS:. We used data from a staffing survey that queried respondents (n = 596 ICUs) on provider (intensivist and nonintensivist), nursing, respiratory therapist, and clinical pharmacist availability and roles. We used latent class analysis to identify clusters describing interprofessional staffing patterns and then compared ICU and hospital characteristics across clusters. MEASUREMENTS AND MAIN RESULTS:. We identified three clusters as optimal. Most ICUs (54.2%) were in cluster 1 (“higher overall staffing”) characterized by a higher likelihood of good provider coverage (both intensivist [onsite 24 hr/d] and nonintensivist [orders placed by ICU team exclusively, presence of advanced practice providers, and physicians-in-training]), nursing leadership (presence of charge nurse, nurse educators, and managers), and bedside nursing support (nurses with registered nursing degrees, fewer patients per nurse, and nursing aide availability). One-third (33.7%) were in cluster 2 (“lower intensivist coverage & nursing leadership, higher bedside nursing support”) and 12.1% were in cluster 3 (“higher provider coverage & nursing leadership, lower bedside nursing support”). Clinical pharmacists were more common in cluster 1 (99.4%), but present in greater than 85% of all ICUs; respiratory therapists were nearly universal. Cluster 1 ICUs were larger (median 20 beds vs. 15 and 17 in clusters 2 and 3, respectively; p < 0.001), and in larger (> 250 beds: 80.6% vs. 66.1% and 48.5%; p < 0.001), not-for-profit (75.9% vs. 69.4% and 60.3%; p < 0.001) hospitals. Telemedicine use 24 hr/d was more common in cluster 3 units (71.8% vs. 11.7% and 14.1%; p < 0.001). CONCLUSIONS:. More than half of U.S. ICUs had higher staffing overall. Others tended to have either higher provider presence and nursing leadership or higher bedside nursing support, but not both.
Published: 2024
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2. Opioid Administration Practice Patterns in Patients With Acute Respiratory Failure Who Undergo Invasive Mechanical Ventilation

Author: Laura C. Myers, MD, MPH, Nicholas A. Bosch, MD, MSc, Lauren Soltesz, MS, Kathleen A. Daly, BS, Cynthia I. Campbell, PhD, Emma Schwager, PhD, Emmanuele Salvati, PhD, Jennifer P. Stevens, MD, MS, Hannah Wunsch, MD, MSc, Justin M. Rucci, MD, S. Reza Jafarzadeh, PhD, Vincent X. Liu, MD, MSc, and Allan J. Walkey, MD, MSc
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES:. To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES:. We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS:. We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3–11%) and 39% (95% CI, 28–49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129–1341 µg) in the KPNC cohort and 200 µg (IQR, 0–1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1–7%) and 20% (95% CI, 15–26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE:. In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals’ analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.
Published: 2024
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3. The incidence of postoperative vasopressor usage: protocol for a prospective international observational cohort study (SQUEEZE)

Author: Ben Creagh-Brown, Hannah Wunsch, Peter Martin, Pierre Harlet, Lui Forni, S. Ramani Moonesinghe, and Ib Jammer
Subjects: Vasopressor, Perioperative, Multicentre, Observational, Postoperative, Incidence, Surgery, RD1-811
Abstract: Abstract Background Postoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilation. The incidence of postoperative vasopressors has never been described for non-cardiac surgery, nor have outcomes associated with their use. This paper presents a protocol for a prospective international cohort study to address these gaps in knowledge. The primary objectives are to estimate the proportion of patients who receive postoperative vasopressor infusions (PVI) and to document the variation in this proportion between hospitals and internationally. Furthermore, we will identify factors in variation of care (patient, condition, surgery, and intraoperative management) associated with receipt of PVI and investigate how PVI use is associated with patient outcomes, including organ dysfunction, length of hospital stay, and 30-day in-hospital mortality. Method This will be a prospective, international, multicentre cohort study that includes all adult (≥ 18 years) non-cardiac surgical patients in participating centres. Patients undergoing cardiac, obstetric, or day-case surgery will be excluded. We will recruit two cohorts of patients: cohort A will include all eligible patients admitted to participating hospitals for seven consecutive days. Cohort B will include 30 sequential patients per hospital, with the single additional inclusion criterion of postoperative vasopressor usage. We expect to collect data on approximately 40,000 patients for cohort A and 12,800 patients for cohort B. Discussion While in cardiac surgery, clinical trials have informed the choice of vasopressors used to treat postoperative vasoplegia; there remains equipoise over the best approach in non-cardiac surgery. Our study will represent the first large-scale assessment of the use of vasopressors after non-cardiac surgery. These data will inform future studies, including trials of different vasopressors and potential management options to improve outcomes and reduce resource use after surgery. Trial registration ClinicalTrials.gov Identifier: NCT03805230, 15 January 2019.
Published: 2023
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4. Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts

Author: Christopher J. Yarnell, Federico Angriman, Bruno L. Ferreyro, Kuan Liu, Harm Jan De Grooth, Lisa Burry, Laveena Munshi, Sangeeta Mehta, Leo Celi, Paul Elbers, Patrick Thoral, Laurent Brochard, Hannah Wunsch, Robert A. Fowler, Lillian Sung, and George Tomlinson
Subjects: Hypoxemic respiratory failure, Intensive care medicine, Mechanical ventilation, Noninvasive ventilation, Thresholds for invasive ventilation, Target trial emulation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. Methods This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008–2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003–2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF
Published: 2023
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5. New opioid use and risk of opioid-related adverse events among adults with intellectual and developmental disabilities in Ontario, Canada

Author: Qi Guan, Siyu Men, Yona Lunsky, David N. Juurlink, Susan E. Bronskill, Hannah Wunsch, and Tara Gomes
Subjects: Drug interactions and side-effects, drugs of dependence disorders, epidemiology, intellectual disability, opiate disorders, Psychiatry, RC435-571
Abstract: Background Individuals with intellectual and developmental disability (IDD) can have a high prevalence of pain, which can be managed with prescription opioids. However, the prevalence of substance use disorder is also high in this population, raising concern about opioid-related adverse events. Aims To assess the risk of opioid-related adverse events following opioid initiation among adults with versus without IDD. Method We conducted a population-based, propensity score matched cohort study on all adults starting prescription opioid therapy in Ontario, Canada, between January 2013 and December 2018. The outcomes of interest were opioid toxicity, new opioid use disorder (OUD) diagnosis and dose escalation (≥90 mg morphine or equivalent) in the year after opioid initiation. We used Cox proportional hazards models to assess the association between IDD diagnosis and each outcome. Results The hazards of opioid toxicity and OUD were significantly higher in those with IDD compared with those without IDD in unmatched analyses (opioid toxicity hazard ratio 3.19, 95% CI 2.81–5.18; OUD hazard ratio 2.36, 95% CI 2.10–2.65), whereas the hazard of dose escalation was significantly lower (hazard ratio 0.76, 95% CI 0.66–0.88). Findings were no longer significant in propensity score matched models for opioid toxicity and dose escalation, whereas the hazard of OUD diagnosis was attenuated substantially in those with IDD (hazard ratio 0.79, 95% CI 0.68–0.91). Conclusions IDD diagnosis is not a driver of opioid-related harm. The increased risk we observed is likely driven by various risk factors often present in this population.
Published: 2022
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6. Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis

Author: Bruno L. Ferreyro, Federico Angriman, Laveena Munshi, Lorenzo Del Sorbo, Niall D. Ferguson, Bram Rochwerg, Michelle J. Ryu, Refik Saskin, Hannah Wunsch, Bruno R. da Costa, and Damon C. Scales
Subjects: Hypoxia, Noninvasive ventilation, Oxygen, Oxygen inhalation therapy, Respiratory insufficiency, Medicine
Abstract: Abstract Background Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Methods We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. Discussion This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure. Systematic review registration PROSPERO CRD42019121755
Published: 2020
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7. Identification and Assessment of Strategies to Address Gender Inequity in the Specialty of Critical Care Medicine: A Scoping Review, Modified Consensus Process, and Stakeholder Meeting

Author: Jeanna Parsons Leigh, PhD, Chloe de Grood, MSc, Rebecca Brundin-Mather, MASc, Alexandra Dodds, MPH, Emily A. FitzGerald, MSc, Laryssa Kemp, MSc, Sara J. Mizen, MA, Liam Whalen-Browne, MBT, Henry T. Stelfox, MD, PhD, Kirsten M. Fiest, PhD, on behalf of the Canadian Critical Care Gender Equity Forum Panel, Jeanna Parsons Leigh, Sofia Ahmed, Rebecca Aslakson, Kali Barrett, Jill Ola Barter, Rosaleen Baruah, Marie-Claude Battista, Karen J. Bosma, Karen E. A. Burns, Laurent Jean Brochard, Han-Oh Chung, Deborah Cook, Andréanne Côté, Joanna C. Dionne, John Drover, Ghislaine Douflé, James Downar, Shelley Duggan, Robert Fowler, Allan Garland, Elaine Gilfoyle, Gillian Hawker, Margaret Herridge, Kimia Honarmand, Tim Karachi, Joann Kawchuk, Rachel G. Khadaroo, Abigail Lara, Sangeeta Mehta, Tina Mele, Kusum Menon, Srinivas Murthy, David Neilipovitz, Kendiss Olafson, Tony O’Leary, Bojan Paunovic, Clare Ramsey, Alison Fox-Robichaud, Francesca Rubulotta, Khara Sauro, Damon Scales, Sharon Straus, Jennifer Tsang, Hannah Wunsch, Samara Zavalkoff, Janice Zimmerman, Kirsten Fiest, and, and Henry Thomas Stelfox
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. We sought to identify and prioritize improvement strategies that Critical Care Medicine (CCM) programs could use to inform and advance gender equity among physicians in CCM. DESIGN:. This study involved three sequential phases: 1) scoping review that identified strategies to improve gender equity in all medical specialties; 2) modified consensus process with 48 CCM stakeholders to rate and rank identified strategies; and 3) in-person stakeholder meeting to refine strategies and discuss facilitators and barriers to their implementation. SETTING:. CCM. SUBJECTS:. CCM stakeholders (physicians, researchers, and decision-makers; mutually inclusive). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We identified 190 unique strategies from 416 articles. Strategies were grouped thematically into 20 categories across four overarching pillars of equity: access, participation, reimbursement, and culture. Participants prioritized 22 improvement strategies for implementation in CCM. The top-rated strategy from each pillar included: 1) nominate gender diverse candidates for faculty positions and prestigious opportunities (equitable access); 2) mandate training in unconscious bias and equitable treatment for committee (e.g., hiring, promotion) members (equitable participation); 3) ensure equitable starting salaries regardless of sex or gender (equitable reimbursement); and, 4) conduct 360° evaluations of leaders (including their direct work circle of supervisors, peers, and subordinates) through a diversity lens (equitable culture). Interprofessional collaboration, leadership, and local champions were identified as key enablers for implementation. CONCLUSIONS:. We identified stakeholder-prioritized strategies that can be used to inform and enhance gender equity among physicians in CCM under four overarching equity pillars: access, participation, reimbursement, and culture. Implementation approaches should include education, policy creation, and measurement, and reporting.
Published: 2022
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8. Getting out of the 1950s: rethinking old priorities for staffing in critical care

Author: Hannah Wunsch
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2020
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9. Acute healthcare resource utilization by age: A cohort study.

Author: Bourke W Tillmann, Longdi Fu, Andrea D Hill, Damon C Scales, Robert A Fowler, Brian H Cuthbertson, and Hannah Wunsch
Subjects: Medicine, Science
Abstract: BackgroundGranular data related to the likelihood of individuals of different ages accessing acute and critical care services over time is lacking.MethodsWe used population-based, administrative data from Ontario to identify residents of specific ages (20, 30, 40, etc. to 100) on January 1st every year from 1995-2019. We assessed rates of emergency department (ED) visits (2003-19), hospitalizations, intensive care unit (ICU) admissions (2003-19), and mechanical ventilation.FindingsOverall the 25-year study period, ED were the most common acute healthcare encounter with 100-year-olds having the lowest rate (138.7/1,000) and 90-year-olds the highest (378.5/1,000). Rates of hospitalization ranged from 24.2/1,000 for those age 20 up to 224.9/1,000 for those age 90. Rates of ICU admission and mechanical ventilation were lowest for those age 20 (1.0 and 0.4/1,000), more than tripled by age 50 (3.3 and 1.7/1,000) and peaked at age 80 (20.3 and 10.1/1,000). Over time rates of ED visits increased (164.3 /1,000 in 2003 vs 199.1 /1,000 in 2019) as did rates of invasive mechanical ventilation (2.0/1,000 in 1995 vs 2.9/1,000 in 2019), whereas rates of ICU admission remained stable (4.8/1,000 in 2003 vs 4.9/1,000 in 2019) and hospitalization declined (66.8/1,000 in 1995 vs 51.5/1,000 in 2019). Age stratified analysis demonstrated that rates of ED presentation increased for those age 70 and younger while hospitalization decreased for all age groups; ICU admission and mechanical ventilation rates changed variably by age, with increasing rates demonstrated primarily among people under the age of 50.InterpretationRates of hospitalizations have decreased over time across all age groups, whereas rates of ED presentation, ICU admissions, and mechanical ventilation have increased, primarily driven by younger adults. These findings suggest that although the delivery of healthcare may be moving away from inpatient medicine, there is a growing population of young adults requiring significant healthcare resources.
Published: 2021
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10. Recovery after critical illness: putting the puzzle together—a consensus of 29

Author: Elie Azoulay, Jean-Louis Vincent, Derek C. Angus, Yaseen M. Arabi, Laurent Brochard, Stephen J. Brett, Giuseppe Citerio, Deborah J. Cook, Jared Randall Curtis, Claudia C. dos Santos, E. Wesley Ely, Jesse Hall, Scott D. Halpern, Nicholas Hart, Ramona O. Hopkins, Theodore J. Iwashyna, Samir Jaber, Nicola Latronico, Sangeeta Mehta, Dale M. Needham, Judith Nelson, Kathleen Puntillo, Michael Quintel, Kathy Rowan, Gordon Rubenfeld, Greet Van den Berghe, Johannes Van der Hoeven, Hannah Wunsch, and Margaret Herridge
Subjects: Mechanical ventilation, Sedation, Delirium, Weakness, Intensive care, Muscular disorder, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.
Published: 2017
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11. Care at a non-university hospital: an independent risk factor for mortality in ARDS?

Author: Bourke Tillmann and Hannah Wunsch
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2017
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12. Hospital admission on weekends for patients who have surgery and 30-day mortality in Ontario, Canada: A matched cohort study.

Author: James D O'Leary, Hannah Wunsch, Anne-Marie Leo, David Levin, Asad Siddiqui, and Mark W Crawford
Subjects: Medicine
Abstract: 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.
Published: 2019
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13. Linking Hospital and Tax data to support research on the economic impacts of hospitalization

Author: Claudia Sanmartin, Alexander Reicker, Allan Garland, Theodore Iwashyna, Randy Fransoo, Damon Scales, Hannah Wunsch, Evelyn Forget, and Hanqing Qiu
Subjects: Demography. Population. Vital events, HB848-3697
Abstract: ABSTRACT Objectives This project links data on acute inpatient hospitalizations from the Canadian Discharge Abstract Database (DAD) with data on income and employment from various taxation- and employment-based administrative files. The goal was to create a linked database that will support research on the labour market and financial outcomes experienced by individuals and families following acute illness requiring hospitalization. Approach Data from the 1999/00 to 2014/15 Discharge Abstract Database (DAD) were linked to the 1981-2013/14 T1 Tax filer data and the Canadian Child Tax Benefit data. We sought to create a unique association between Health Insurance Numbers (HIN) available in the DAD and Social Insurance Numbers (SIN) available in the tax data by using variables common to both data sets – date of birth, postal code and sex. Both transactional data sets were “individualized” such that unique combinations of the linkage variables were identified and eligible for linkage. The linkage was conducted using deterministic methods. Results Approximately 97% of combinations involving date of birth, postal code and sex in the hospitalization data were uniquely related to a single valid HIN (n=18.8 million). Similarly, approximately 96% of the keys on the Tax data file were associated with a unique person. Approximately 86% of HINs were associated with a unique identifier in the tax file and these HINs account for approximately 83% of the hospital records. The linkage was consistent over time, with linkage rates between 85% and 88% of HINs for all years. Some variation in linkage rates were observed by jurisdiction and by age. (Error estimates to be reported) Conclusion This project has created a unique linked database that will support research on the economic consequences of ‘health shocks’ for individuals and their families, and the implications for income, labour and health policies. This database represents a new and unique resource that will fill an important national data gap, and enable a wide range of relevant research.
Published: 2017
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14. Optimizing Administrative Datasets to Examine Acute Kidney Injury in the Era of Big Data: Workgroup Statement from the 15 ADQI Consensus Conference

Author: Edward D. Siew, Rajit K. Basu, Hannah Wunsch, Andrew D. Shaw, Stuart L Goldstein, Claudio Ronco, John A. Kellum, and Sean M. Bagshaw
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Abstract: Purpose of review: The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field. Objectives: 1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable “communication” and “translation” within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform ‘registry-based’ pragmatic studies. Source of information: Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI. Setting: Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7 th , 2015, Banff, Canada Patients: Hospitalized patients with AKI Key messages: The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI) its temporal trends and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care. Methods: A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions. Results: Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to implement, improving standardization of reporting by using laboratory-based definitions and providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies. Limitations: Data sources largely restricted to North American and Europe Implications: Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. Why is this review important?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. What are the key messages?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care.
Published: 2016
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15. The Autumn Ghost: How the Battle Against a Polio Epidemic Revolutionized Modern Medical Care

Author: Hannah Wunsch
Published: 2023

16. Palliative Care in the Intensive Care Unit: Past, Present, and Future

Author: James Downar, May Hua, and Hannah Wunsch
Subjects: General Medicine, Critical Care and Intensive Care Medicine
Published: 2023
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17. Inhaled Nitric Oxide vs Epoprostenol During Acute Respiratory Failure

Author: Nicholas A. Bosch, Anica C. Law, Emily A. Vail, Kari R. Gillmeyer, Hayley B. Gershengorn, Hannah Wunsch, and Allan J. Walkey
Subjects: Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2022
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18. Nonopioid Analgesic Prescriptions Filled after Surgery among Older Adults in Ontario, Canada: A Population-based Cohort Study

Author: Naheed K, Jivraj, Karim, Ladha, Akash, Goel, Andrea, Hill, Duminda N, Wijeysundera, Brian T, Bateman, Mark, Neuman, and Hannah, Wunsch
Subjects: Anesthesiology and Pain Medicine
Abstract: Background The objective was to assess changes over time in prescriptions filled for nonopioid analgesics for older postoperative patients in the immediate postdischarge period. The authors hypothesized that the number of patients who filled a nonopioid analgesic prescription increased during the study period. Methods The authors performed a population-based cohort study using linked health administrative data of 278,366 admissions aged 66 yr or older undergoing surgery between fiscal year 2013 and 2019 in Ontario, Canada. The primary outcome was the percentage of patients with new filled prescriptions for nonopioid analgesics within 7 days of discharge, and the secondary outcome was the analgesic class. The authors assessed whether patients filled prescriptions for a nonopioid only, an opioid only, both opioid and nonopioid prescriptions, or a combination opioid/nonopioid. Results Overall, 22% (n = 60,181) of patients filled no opioid prescription, 2% (n = 5,534) filled a nonopioid only, 21% (n = 59,608) filled an opioid only, and 55% (n = 153,043) filled some combination of opioid and nonopioid. The percentage of patients who filled a nonopioid prescription within 7 days postoperatively increased from 9% (n = 2,119) in 2013 to 28% (n = 13,090) in 2019, with the greatest increase for acetaminophen: 3% (n = 701) to 20% (n = 9,559). The percentage of patients who filled a combination analgesic prescription decreased from 53% (n = 12,939) in 2013 to 28% (n = 13,453) in 2019. However, the percentage who filled both an opioid and nonopioid prescription increased: 4% (n = 938) to 21% (n = 9,880) so that the overall percentage of patients who received both an opioid and a nonopioid remained constant over time 76% (n = 18,642) in 2013 to 75% (n = 35,391) in 2019. Conclusions The proportion of postoperative patients who fill prescriptions for nonopioid analgesics has increased. However, rather than a move to use of nonopioids alone for analgesia, this represents a shift away from combination medications toward separate prescriptions for opioids and nonopioids. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2022
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19. Opioid Initiation and the Hazard of Falls or Fractures Among Older Adults with Varying Levels of Central Nervous System Depressant Burden

Author: Qi Guan, Siyu Men, David N. Juurlink, Susan E. Bronskill, Hannah Wunsch, and Tara Gomes
Subjects: Analgesics, Opioid, Ontario, Fractures, Bone, Anti-Inflammatory Agents, Non-Steroidal, Central Nervous System Depressants, Humans, Pharmacology (medical), Geriatrics and Gerontology, Aged, Central Nervous System Agents
Abstract: Co-prescription of opioids with other central nervous system (CNS) depressants is common but the combination may increase the risk for adverse events such as falls and fractures, particularly among older adults. We explored the risk of fall- or fracture-related hospital visits after opioid initiation among older adults with varying degrees of concomitant CNS depressant burden.We used population-based administrative health data from Ontario, Canada, to examine the relationship between hospital visits for falls or fractures at different levels of CNS burden among individuals aged 66 and older who started prescription opioids between March 1, 2008, and March 31, 2019. For comparison, we identified individuals starting prescription non-steroidal anti-inflammatory drugs (NSAIDs). The outcome was a hospital visit for falls or fractures within 14 days after starting analgesic therapy. We stratified the cohort according to additional CNS burden: none, low (one concurrent CNS depressant drug class) and high (≥ 2 concurrent CNS depressant classes) on the index date. We balanced opioid and NSAID recipients using inverse probability of treatment weighting and reported weighted hazard ratios from Cox proportional hazards models. We then used pairwise comparisons to determine differences between hazard ratios at different levels of CNS burden.The cohort included 1,066,692 older adults, with 562,692 new opioid recipients and 504,000 new NSAID recipients. Among opioid recipients, 83 % had no additional CNS burden, 13 % had low burden and 4 % had high burden. The short-term rate of falls or fractures for new opioid recipients increased by CNS burden from 97 per 1000 person-years (no burden) to 233 per 1000 person-years (high CNS burden). Opioid recipients had a similarly elevated hazard of falls or fractures within each CNS burden level compared to NSAID recipients (adjusted hazard ratio [aHR] 1.62, 95 % CI 1.50-1.76 for no burden; aHR 1.69, 95 % CI 1.45-1.97 for low burden; aHR 1.40, 95 % CI 1.08-1.82 for high burden).Among older adults, initiation of opioids is associated with an increased hazard of falls; however, this hazard is not modified by different levels of CNS depressant burden. This suggests that it remains important for physicians, patients, and caregivers to be vigilant when starting new opioid therapy regardless of other CNS medications taken concurrently.
Published: 2022
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20. Variation in Bed-to-Physician Ratios During Weekday Daytime Hours in ICUs in Australia and New Zealand*

Author: Hannah Wunsch, David V. Pilcher, Edward Litton, Matthew Anstey, Allan Garland, and Hayley B. Gershengorn
Subjects: Intensive Care Units, Critical Illness, Physicians, Personnel Staffing and Scheduling, Humans, Hospital Mortality, Critical Care and Intensive Care Medicine, Retrospective Studies, New Zealand
Abstract: To determine common "bed-to-physician" ratios during weekday hours across ICUs and assess factors associated with variability in this ratio.Retrospective cohort study.All ICUs in Australia/New Zealand that participated in a staffing survey administered in 2017-2018.ICU admissions from 2016 to 2018.We linked survey data with patient-level data. We defined: 1) bed-to-intensivist ratio as the number of usually available ICU beds divided by the number of onsite weekday daytime intensivists; and 2) bed-to-physician ratio as the number of available ICU beds divided by the total number of physicians (intensivists + nonintensivists, including trainees). We calculated the median and interquartile range (IQR) of bed-to-intensivist ratio and bed-to-physician ratios during weekday hours. We assessed variability in each by type of hospital and ICU and by severity of illness of patients, defined by the predicted hospital mortality.None.Of the 123 (87.2%) of Australia/New Zealand ICUs that returned staffing surveys, 114 (92.7%) had an intensivist present during weekday daytime hours, and 116 (94.3%) reported at least one nonintensivist physician. The median bed-to-intensivist ratio was 8.0 (IQR, 6.0-11.4), which decreased to a bed-to-physician ratio of 3.0 (IQR, 2.2-4.9). These ratios varied with mean severity of illness of the patients in the unit. The median bed-to-intensivist ratio was highest (13.5) for ICUs with a mean predicted mortalitygt; 2-4%, and the median bed-to-physician ratio was highest (5.7) for ICUs with a mean predicted mortality ofgt; 4-6%. Both ratios decreased and plateaued in ICUs with a mean predicted mortality for patients greater than 8% (median bed-to-intensivist ratio range, 6.8-8.0, and bed-to-physician ratio range of 2.4-2.7).Weekday bed-to-physician ratios in Australia/New Zealand ICUs are lower than the bed-to-intensivist ratios and have a relatively fixed ratio of less than 3 for units taking care of patients with a higher average severity of illness. These relationships may be different in other countries or healthcare systems.
Published: 2022
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21. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Author: Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, Assem, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Ali Zeggwagh, Amine, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Kumar Agrawal, Vijay, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Manuel Allegue, Jose, Alvarez, Diana, Amador, Joaquin, H Andersen, Finn, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Milagrito Avalos Cabrera, Jesu, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elia, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Emilio Barrueco-Francioni, Jesu, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Lui, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Roberto Bettini, Lisandro, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, M Bojanowski, Christine, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, J Bosma, Karen, Bottiroli, Maurizio, Boyd, Owen, Bozbay, Suha, Briva, Arturo, Brochard, Laurent, Bruel, Cédric, Bruni, Andrea, Buehner, Ulrike, Bulpa, Pierre, Burt, Karen, Buscot, Mathieu, Buttera, Stefania, Cabrera, Jorge, Caccese, Roberta, Caironi, Pietro, Canchos Gutierrez, Ivan, Canedo, Nancy, Cani, Alma, Cappellini, Iacopo, Carazo, Jesu, Pablo Cardonnet, Lui, Carpio, David, Carriedo, Demetrio, Carrillo, Ramón, Carvalho, João, Caser, Eliana, Castelli, Antonio, Castillo Quintero, Manuel, Castro, Heloisa, Catorze, Nuno, Cengiz, Melike, Cereijo, Enrique, Ceunen, Helga, Chaintoutis, Christo, Chang, Youjin, Chaparro, Gustavogcha, Chapman, Carmel, Chau, Simon, Eugenia Chavez, Cecilia, Chelazzi, Cosimo, Chelly, Jonathan, Chemouni, Frank, Chen, Kai, Chena, Ariel, Chiarandini, Paolo, Chilton, Phil, Chiumello, Davide, Chou-Lie, Yvette, Chudeau, Nicola, Cinel, Ismail, Cinnella, Gilda, Clark, Michele, Clark, Thoma, Clementi, Stefano, Coaguila, Lui, Jaspe Codecido, Alexi, Collins, Amy, Colombo, Riccardo, Conde, Juan, Consales, Guglielmo, Cook, Tim, Coppadoro, Andrea, Cornejo, Rodrigo, Cortegiani, Andrea, Coxo, Cristina, Neville Cracchiolo, Andrea, Crespo Ramirez, Mónica, Crova, Philippe, Cruz, José, Cubattoli, Lucia, Çukurova, Zafer, Curto, Francesco, Czempik, Piotr, D'Andrea, Rocco, da Silva Ramos, Fernando, Dangers, Laurence, Danguy des Déserts, Marc, Danin, Pierre-Eric, Dantas, Fabianne, Daubin, Cédric, Dawei, Wu, de Haro, Candelaria, de Jesus Montelongo, Felipe, De Mendoza, Diego, de Pablo, Raúl, De Pascale, Gennaro, De Rosa, Silvia, Decavèle, Maxen, Declercq, Pierre-Loui, Deicas, Alberto, Del Carmen Campos Moreno, María, Dellamonica, Jean, Delmas, Benjamin, Demirkiran, Oktay, Demirkiran, Hilmi, Dendane, Tarek, di Mussi, Rossella, Diakaki, Chrysi, Diaz, Anatilde, Diaz, Willy, Dikmen, Yalim, Dimoula, Aikaterini, Doble, Patricia, Doha, Nagwa, Domingos, Guilherme, Dres, Martin, Dries, David, Duggal, Abhijit, Duke, Graeme, Dunts, Pavel, Dybwik, Knut, Dykyy, Maksym, Eckert, Philippe, Efe, Serdar, Elatrous, Souheil, Elay, Gülseren, S Elmaryul, Abubaker, Elsaadany, Mohamed, Elsayed, Hany, Elsayed, Samar, Emery, Malo, Ena, Sébastien, Eng, Kevin, A Englert, Joshua, Erdogan, Elif, Ergin Ozcan, Perihan, Eroglu, Ege, Escobar, Miguel, Esen, Figen, Esen Tekeli, Arzu, Esquivel, Alejandro, Esquivel Gallegos, Helbert, Ezzouine, Hanane, Facchini, Alberto, Faheem, Mohammad, Fanelli, Vito, Fernanda Farina, Maria, Fartoukh, Muriel, Fehrle, Lutz, Feng, Feng, Feng, Yufeng, Fernandez, Irene, Fernandez, Borja, Lorena Fernandez-Rodriguez, Maria, Ferrando, Carlo, João Ferreira da Silva, Maria, Ferreruela, Mireia, Ferrier, Janet, Jesús Flamm Zamorano, Matia, Flood, Laura, Floris, Leda, Fluckiger, Martin, Forteza, Catalina, Fortunato, Antonella, Frans, Eric, Frattari, Antonella, Fredes, Sebastian, Frenzel, Tim, Fumagalli, Roberto, Andres Furche, Mariano, Fusari, Maurizio, Fysh, Edward, Luis Galeas-Lopez, Juan, Galerneau, Louis-Marie, Garcia, Analía, Fernanda Garcia, María, Garcia, Elisabet, Garcia Olivares, Pablo, Garlicki, Jaroslaw, Garnero, Aude, Garofalo, Eugenio, Gautam, Prabha, Gazenkampf, Andrey, Gelinotte, Stéphanie, Gelormini, Domenico, Ghrenassia, Etienne, Giacomucci, Angelo, Giannoni, Robert, Gigante, Andrea, Glober, Nancy, Gnesin, Paolo, Gollo, Yari, Gomaa, Dina, Gomero Paredes, Rosita, Gomes, Rui, Alejandro Gomez, Raúl, Gomez, Oscar, Gomez, Aroa, Gondim, Louise, Gonzalez, Manuel, Gonzalez, Isabel, Gonzalez-Castro, Alejandro, Gordillo Romero, Orlando, Gordo, Federico, Gouin, Philippe, Graf Santos, Jerónimo, Grainne, Rooney, Grando, Matilde, Granov Grabovica, Sanja, Grasso, Salvatore, Grasso, Rinaldo, Grimmer, Lisa, Grissom, Colin, Gu, Qing, Guan, Xiang-Dong, Guarracino, Fabio, Guasch, Neu, Guatteri, Luca, Gueret, Renaud, Guérin, Claude, Guerot, Emmanuel, Guitard, Pierre-Gilda, Gül, Fethi, Gumus, Ayca, Gurjar, Mohan, Gutierrez, Patricia, Hachimi, Abdelhamid, Hadzibegovic, Adi, Hagan, Samantha, Hammel, Clare, Han Song, Joo, Hanlon, Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Omar Heredia Orbegoso, Gabriel, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Lui, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Carmen Hornos, M, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Loui, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicola, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagioti, Antonio Iotti, Giorgio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Alberto Jaramillo, Lui, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Anders Johnstad, Bror, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Hugo Madrigal Robles, Victor, Maurizio Maggiore, Salvatore, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Del Carmen Marin, Maria, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, Mccredie, Victoria, Mccullough, Jame, Mcguinness, Shay, Mckown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Khalaf Ebraheim Mervat, Mohamed, Michaux, Isabelle, Mikhaeil, Michael, Milagros, Olga, Milet, Igor, Teresa Millan, Maria, Minwei, Zhang, Mirabella, Lucia, Mishra, Sanghamitra, Mistraletti, Giovanni, Mochizuki, Katsunori, Moghal, Arif, Mojoli, Francesco, Molin, Alexandre, Montiel, Raquel, Montini, Luca, Monza, Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Rolando Morocho Tutillo, Diego, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlo, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Antonio Namendys-Silva, Silvio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Teresa Oliveira, Maria, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Cristina Orlandi, Maria, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Özyilmaz, Ezgi, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Luis Palazon Sanchez, Eugenio, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, J Parrilla, Francisco, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Lui, Patel, Mayur, Patel, Grisma, Kumar Pati, Basanta, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Alejandra Pavlotsky, Vanesa, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlo, Gabriela Peña Padilla, Andrea, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, Françoi, Picetti, Edoardo, Pierucci, Elisabetta, Piervincenzi, Edoardo, Pinciroli, Riccardo, Pintado, Maria-Consuelo, Piraino, Thoma, Piras, Stephanie, Piras, Claudio, Pirompanich, Pattarin, Pisani, Luigi, Platas, Enrique, Plotnikow, Gustavo, Porras, Willy, Porta, Virginia, Portilla, Mariana, Portugal, José, Povoa, Pedro, Prat, Gwenael, Pratto, Romina, Preda, Gabriel, Prieto, Isidro, Prol-Silva, Estefania, Pugh, Richard, Qi, Yupeng, Qian, Chuanyun, Qin, Tiehe, Qu, Hongping, Quintana, Teobaldo, Quispe Sierra, Rosari, Quispe Soto, Rocio, Rabbani, Raihan, Rabee, Mohamed, Rabie, Ahmed, Augusta Rahe Pereira, Maria, Rai, Ashish, Raj Ashok, Sundar, Rajab, Mostafa, Ramdhani, Navin, Ramey, Elizabeth, Ranieri, Marco, Rathod, Darshana, Ray, Banambar, Mahmud Redwanul Huq, Shihan, Regli, Adrian, Reina, Rosa, Resano Sarmiento, Natalia, Reynaud, Faustine, Rialp, Gemma, Ricart, Pilar, Rice, Todd, Richardson, Angu, Rieder, Marcelo, Rinket, Martin, Rios, Fernando, Risso Vazquez, Alejandro, Riva, Ivano, Rivette, Monaly, Roca, Oriol, Roche-Campo, Ferran, Rodriguez, Covadonga, Rodriguez, Gabriel, Rodriguez Gonzalez, Daniel, Yanina Rodriguez Tucto, Xandra, Rogers, Angela, Elena Romano, María, Rørtveit, Linda, Rose, Alastair, Roux, Damien, Rouze, Anahita, Nahuel Rubatto Birri, Paolo, Ruilan, Wang, Ruiz Robledo, Aldana, Luis Ruiz-Aguilar, Antonio, Sadahiro, Tomohito, Saez, Ignacio, Sagardia, Judith, Saha, Rajnish, Saha, Rohit, Saiphoklang, Narongkorn, Saito, Shigeki, Salem, Maie, Sales, Gabriele, Salgado, Patricia, Samavedam, Sriniva, Sami Mebazaa, Mhamed, Samuelsson, Line, San Juan Roman, Nandyelly, Sanchez, Patricia, Sanchez-Ballesteros, Jesu, Sandoval, Yazcitk, Sani, Emanuele, Santos, Martin, Santos, Carla, Sanui, Masamitsu, Saravanabavan, Lakshmikanthcharan, Sari, Sema, Sarkany, Agne, Sauneuf, Bertrand, Savioli, Monica, Sazak, Hilal, Scano, Riccardo, Schneider, Franci, Schortgen, Frédérique, J Schultz, Marcu, Leonie Schwarz, Gabriele, Seçkin Yücesoy, Faruk, Seely, Andrew, Seiler, Frederik, Seker Tekdos, Yasemin, Seok Chan, Kim, Serano, Luca, 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Mandy, Tamasato, Tamasato, Tang, Zhanhong, Tangsujaritvijit, Viratch, Taniguchi, Leandro, Taniguchi, Daisuke, Tarantino, Fabio, Teerapuncharoen, Krittika, Temprano, Susana, Terragni, Pierpaolo, Terzi, Nicola, Thakur, Anand, Theerawit, Pongdhep, W Thille, Arnaud, Thomas, Matt, Thungtitigul, Poungrat, Thyrault, Martial, Tilouch, Nejla, Timenetsky, Karina, Tirapu, Juna, Todeschini, Manuel, Tomas, Roser, Tomaszewski, Christian, Tonetti, Tommaso, Tonnelier, Alexandre, Trinder, John, Trongtrakul, Konlawij, Truwit, Jonathon, Tsuei, Betty, Tulaimat, Aiman, Turan, Sema, Turkoglu, Melda, Tyagi, Sanjeev, Ubeda, Alejandro, Vagginelli, Federica, Florencia Valenti, María, Vallverdu, Imma, Van Axel, Alisha, van den Hul, Ingrid, van der Hoeven, Han, Van Der Meer, Nardo, Vanhoof, Marc, Vargas-Ordoñez, Mónica, Vaschetto, Rosanna, Vascotto, Ettore, Vatsik, Maria, Vaz, Ana, Vazquez-Sanchez, Antonia, Ventura, Sara, Wytze Vermeijden, Jan, Vidal, Anxela, Vieira, Jocyelle, Vilela Costa Pinto, Bruno, Villagra, Ana, Villegas Succar, Cristina, Georg Vinorum, Ole, Vitale, Giovanni, Vj, Ramesh, Vochin, Ana, Voiriot, Guillaume, Alberto Volta, Carlo, von Seth, Magnu, Wajdi, Maazouzi, Walsh, Don, Wang, Shouhong, Wardi, Gabriel, Christian Ween-Velken, Nil, Wei, Bi-Lin, Weller, Dolf, Welsh, Deborah, Welters, Ingeborg, Wert, Michael, Whiteley, Simon, Wilby, Elizabeth, Williams, Erin, Williams, Karen, Wilson, Antoinette, Wojtas, Jadwiga, Won Huh, Jin, Wrathall, David, Wright, Christopher, Wu, Jian-Feng, Xi, Guo, Xing, Zheng-Jiang, Xu, Hongyang, Yamamoto, Kotaro, Yan, Jie, Yáñez, Julio, Yang, Xiaobo, Yates, Elliot, Yazicioglu Mocin, Ozlem, Ye, Zhenglong, Yildirim, Fatma, Yoshida, Norifumi, Higo Leon Yoshido, Hector, Young Lee, Bo, Yu, Rongguo, Yu, Gong, Yu, Tao, Yuan, Boyun, Yuangtrakul, Nadwipa, Yumoto, Tetsuya, Yun, Xie, Zakalik, Graciela, Zaki, Ahmad, Zalba-Etayo, Begoña, Zambon, Massimo, Zang, Bin, Zani, Gianluca, Zarka, Jonathan, Maria Zerbi, Simone, Zerman, Avsar, Zetterquist, Harald, Zhang, Jiuzhi, Zhang, Hongwen, Zhang, Wei, Zhang, Guoxiu, Zhang, Weixin, Zhao, Hongsheng, Zheng, Jia, Zhu, Bin, Zumaran, Ronald, Gennaro De Pascale (ORCID:0000-0002-8255-0676), Luca Montini (ORCID:0000-0003-4602-5134), Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, Assem, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Ali Zeggwagh, Amine, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Kumar Agrawal, Vijay, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Manuel Allegue, Jose, Alvarez, Diana, Amador, Joaquin, H Andersen, Finn, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Milagrito Avalos Cabrera, Jesu, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elia, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Emilio Barrueco-Francioni, Jesu, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Lui, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Roberto Bettini, Lisandro, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, M Bojanowski, Christine, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, J Bosma, 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Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Omar Heredia Orbegoso, Gabriel, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Lui, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Carmen Hornos, M, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Loui, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicola, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagioti, Antonio Iotti, Giorgio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Alberto Jaramillo, Lui, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Anders Johnstad, Bror, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Hugo Madrigal Robles, Victor, Maurizio Maggiore, Salvatore, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Del Carmen Marin, Maria, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, Mccredie, Victoria, Mccullough, Jame, Mcguinness, Shay, Mckown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Khalaf Ebraheim Mervat, Mohamed, Michaux, Isabelle, Mikhaeil, Michael, Milagros, Olga, Milet, Igor, Teresa Millan, Maria, Minwei, Zhang, Mirabella, Lucia, Mishra, Sanghamitra, Mistraletti, Giovanni, Mochizuki, Katsunori, Moghal, Arif, Mojoli, Francesco, Molin, Alexandre, Montiel, Raquel, Montini, Luca, Monza, Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Rolando Morocho Tutillo, Diego, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlo, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Antonio Namendys-Silva, Silvio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Teresa Oliveira, Maria, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Cristina Orlandi, Maria, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Özyilmaz, Ezgi, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Luis Palazon Sanchez, Eugenio, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, J Parrilla, Francisco, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Lui, Patel, Mayur, Patel, Grisma, Kumar Pati, Basanta, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Alejandra Pavlotsky, Vanesa, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlo, Gabriela Peña Padilla, Andrea, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, Françoi, Picetti, Edoardo, Pierucci, Elisabetta, Piervincenzi, Edoardo, Pinciroli, Riccardo, Pintado, Maria-Consuelo, Piraino, Thoma, Piras, Stephanie, Piras, Claudio, Pirompanich, Pattarin, Pisani, Luigi, Platas, Enrique, Plotnikow, Gustavo, Porras, Willy, Porta, Virginia, Portilla, Mariana, Portugal, José, Povoa, Pedro, Prat, Gwenael, Pratto, Romina, Preda, Gabriel, Prieto, Isidro, Prol-Silva, Estefania, Pugh, Richard, Qi, Yupeng, Qian, Chuanyun, Qin, Tiehe, Qu, Hongping, Quintana, Teobaldo, Quispe Sierra, Rosari, Quispe Soto, Rocio, Rabbani, Raihan, Rabee, Mohamed, Rabie, Ahmed, Augusta Rahe Pereira, Maria, Rai, Ashish, Raj Ashok, Sundar, Rajab, Mostafa, Ramdhani, Navin, Ramey, Elizabeth, Ranieri, Marco, Rathod, Darshana, Ray, Banambar, Mahmud Redwanul Huq, Shihan, Regli, Adrian, Reina, Rosa, Resano Sarmiento, Natalia, Reynaud, Faustine, Rialp, Gemma, Ricart, Pilar, Rice, Todd, Richardson, Angu, Rieder, Marcelo, Rinket, Martin, Rios, Fernando, Risso Vazquez, Alejandro, Riva, Ivano, Rivette, Monaly, Roca, Oriol, Roche-Campo, Ferran, Rodriguez, Covadonga, Rodriguez, Gabriel, Rodriguez Gonzalez, Daniel, Yanina Rodriguez Tucto, Xandra, Rogers, Angela, Elena Romano, María, Rørtveit, Linda, Rose, Alastair, Roux, Damien, Rouze, Anahita, Nahuel Rubatto Birri, Paolo, Ruilan, Wang, Ruiz Robledo, Aldana, Luis Ruiz-Aguilar, Antonio, Sadahiro, Tomohito, Saez, Ignacio, Sagardia, Judith, Saha, Rajnish, Saha, Rohit, Saiphoklang, Narongkorn, Saito, Shigeki, Salem, Maie, Sales, Gabriele, Salgado, Patricia, Samavedam, Sriniva, Sami Mebazaa, Mhamed, Samuelsson, Line, San Juan Roman, Nandyelly, Sanchez, Patricia, Sanchez-Ballesteros, Jesu, Sandoval, Yazcitk, Sani, Emanuele, Santos, Martin, Santos, Carla, Sanui, Masamitsu, Saravanabavan, Lakshmikanthcharan, Sari, Sema, Sarkany, Agne, Sauneuf, Bertrand, Savioli, Monica, Sazak, Hilal, Scano, Riccardo, Schneider, Franci, Schortgen, Frédérique, J Schultz, Marcu, Leonie Schwarz, Gabriele, Seçkin Yücesoy, Faruk, Seely, Andrew, Seiler, Frederik, Seker Tekdos, Yasemin, Seok Chan, Kim, Serano, Luca, Serednicki, Wojciech, Setten, Mariano, Shah, Asim, Shah, Bhagyesh, Shang, You, Shanmugasundaram, Pradeep, Shapovalov, Konstantin, Shebl, Eman, Shiga, Takuya, Shime, Nobuaki, Shin, Phil, Short, Jack, Shuhua, Chen, Siddiqui, Sughrat, Ignacio Silesky Jimenez, Juan, Silva, Daniel, Silva Sales, Betania, Simons, Koen, Ågot Sjøbø, Brit, Slessor, David, Smiechowicz, Jakub, Smischney, Nathan, Smith, Paul, Smith, Tim, Smith, Mark, Snape, Sarah, Snyman, Lindi, Soetens, Filiep, Sook Hong, Kyung, Ángel Sosa Medellin, Miguel, Soto, Giovanna, Souloy, Xavier, Sousa, Elsa, Sovatzis, Stefania, Sozutek, Didem, Spadaro, Savino, Spagnoli, Marco, Spångfors, Martin, Spittle, Nick, Spivey, Mike, Stapleton, Andrew, Stefanovic, Branislava, Stephenson, Lorraine, Stevenson, Elizabeth, Strand, Kristian, Teresa Strano, Maria, Straus, Slavenka, Sun, Chenliang, Sun, Rongqing, Sundaram, Venkat, Sunpark, Tai, Surlemont, Elisabeth, Sutherasan, Yuda, Szabo, Zsuzsanna, Tainter, Christopher, Takaba, Akihiro, Tallott, Mandy, Tamasato, Tamasato, Tang, Zhanhong, Tangsujaritvijit, Viratch, Taniguchi, Leandro, Taniguchi, Daisuke, Tarantino, Fabio, Teerapuncharoen, Krittika, Temprano, Susana, Terragni, Pierpaolo, Terzi, Nicola, Thakur, Anand, Theerawit, Pongdhep, W Thille, Arnaud, Thomas, Matt, Thungtitigul, Poungrat, Thyrault, Martial, Tilouch, Nejla, Timenetsky, Karina, Tirapu, Juna, Todeschini, Manuel, Tomas, Roser, Tomaszewski, Christian, Tonetti, Tommaso, Tonnelier, Alexandre, Trinder, John, Trongtrakul, Konlawij, Truwit, Jonathon, Tsuei, Betty, Tulaimat, Aiman, Turan, Sema, Turkoglu, Melda, Tyagi, Sanjeev, Ubeda, Alejandro, Vagginelli, Federica, Florencia Valenti, María, Vallverdu, Imma, Van Axel, Alisha, van den Hul, Ingrid, van der Hoeven, Han, Van Der Meer, Nardo, Vanhoof, Marc, Vargas-Ordoñez, Mónica, Vaschetto, Rosanna, Vascotto, Ettore, Vatsik, Maria, Vaz, Ana, Vazquez-Sanchez, Antonia, Ventura, Sara, Wytze Vermeijden, Jan, Vidal, Anxela, Vieira, Jocyelle, Vilela Costa Pinto, Bruno, Villagra, Ana, Villegas Succar, Cristina, Georg Vinorum, Ole, Vitale, Giovanni, Vj, Ramesh, Vochin, Ana, Voiriot, Guillaume, Alberto Volta, Carlo, von Seth, Magnu, Wajdi, Maazouzi, Walsh, Don, Wang, Shouhong, Wardi, Gabriel, Christian Ween-Velken, Nil, Wei, Bi-Lin, Weller, Dolf, Welsh, Deborah, Welters, Ingeborg, Wert, Michael, Whiteley, Simon, Wilby, Elizabeth, Williams, Erin, Williams, Karen, Wilson, Antoinette, Wojtas, Jadwiga, Won Huh, Jin, Wrathall, David, Wright, Christopher, Wu, Jian-Feng, Xi, Guo, Xing, Zheng-Jiang, Xu, Hongyang, Yamamoto, Kotaro, Yan, Jie, Yáñez, Julio, Yang, Xiaobo, Yates, Elliot, Yazicioglu Mocin, Ozlem, Ye, Zhenglong, Yildirim, Fatma, Yoshida, Norifumi, Higo Leon Yoshido, Hector, Young Lee, Bo, Yu, Rongguo, Yu, Gong, Yu, Tao, Yuan, Boyun, Yuangtrakul, Nadwipa, Yumoto, Tetsuya, Yun, Xie, Zakalik, Graciela, Zaki, Ahmad, Zalba-Etayo, Begoña, Zambon, Massimo, Zang, Bin, Zani, Gianluca, Zarka, Jonathan, Maria Zerbi, Simone, Zerman, Avsar, Zetterquist, Harald, Zhang, Jiuzhi, Zhang, Hongwen, Zhang, Wei, Zhang, Guoxiu, Zhang, Weixin, Zhao, Hongsheng, Zheng, Jia, Zhu, Bin, Zumaran, Ronald, Gennaro De Pascale (ORCID:0000-0002-8255-0676), and Luca Montini (ORCID:0000-0003-4602-5134)
Abstract: Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 d
Published: 2023

22. Tendances de la prescription d’opioïdes postopératoires en Ontario entre 2013 et 2019 : une étude de cohorte axée sur la population

Author: Naheed K. Jivraj, Karim Ladha, Akash Goel, Andrea Hill, Duminda N. Wijeysundera, Brian T. Bateman, and Hannah Wunsch
Subjects: Anesthesiology and Pain Medicine, General Medicine
Published: 2022
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23. Reducing Central Venous Catheter Use Through Adoption of Guidelines for Peripheral Catheter-based Vasopressor Delivery

Author: Sakshi Gandotra, Hannah Wunsch, Nicholas A Bosch, Allan Walkey, and Bijan Teja
Subjects: Pulmonary and Respiratory Medicine
Published: 2023
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24. Arterial pressure response to an increase in norepinephrine varies depending on the baseline norepinephrine dose in patients with septic shock

Author: Nicholas A. Bosch, Bijan Teja, Anica C. Law, Hannah Wunsch, and Allan J. Walkey
Subjects: Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2023
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25. Preface

Author: Hannah Wunsch
Subjects: General Medicine, Critical Care and Intensive Care Medicine
Published: 2023
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26. Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis*

Author: Claudio M, Martin, Melody, Lam, Britney, Le, Ruxandra, Pinto, Vincent, Lau, Ian M, Ball, Hannah, Wunsch, Robert A, Fowler, and Damon C, Scales
Subjects: Cohort Studies, Intensive Care Units, Critical Care, Humans, Emergency Service, Hospital, Critical Care and Intensive Care Medicine, Patient Readmission, Patient Discharge, Retrospective Studies
Abstract: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario.Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV.ICUs in Ontario.Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017.DDH from ICU.Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ± 0.03 ( se ); p = 0.3).There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.
Published: 2022
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27. Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study

Author: Federico Angriman, Laura C. Rosella, Patrick R. Lawler, Dennis T. Ko, Hannah Wunsch, and Damon C. Scales
Subjects: Critical Care and Intensive Care Medicine
Published: 2022
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28. Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study

Author: Christopher J. Yarnell, Alistair Johnson, Tariq Dam, Annemijn Jonkman, Kuan Liu, Hannah Wunsch, Laurent Brochard, Leo Anthony Celi, Harm-Jan De Grooth, Paul Elbers, Sangeeta Mehta, Laveena Munshi, Robert A. Fowler, Lillian Sung, George Tomlinson, Intensive care medicine, ACS - Microcirculation, Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, AII - Cancer immunology, and CCA - Cancer biology and immunology
Subjects: Pulmonary and Respiratory Medicine, Critical Care and Intensive Care Medicine
Abstract: Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of
Published: 2023
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29. New and Persistent Sedative Prescriptions Among Older Adults Following a Critical Illness

Author: Lisa D. Burry, Chaim M. Bell, Andrea Hill, Ruxandra Pinto, Damon C. Scales, Susan E. Bronskill, David Williamson, Louise Rose, Longdi Fu, Robert Fowler, Claudio M. Martin, Lisa Dolovich, and Hannah Wunsch
Subjects: Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published: 2023
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30. Association of patient-to-intensivist ratio with hospital mortality in Australia and New Zealand

Author: Edward Litton, Hannah Wunsch, David Pilcher, Matthew Anstey, Allan Garland, and Hayley B. Gershengorn
Subjects: medicine.medical_specialty, Census, Original, Intensivist, Workload, Critical Care and Intensive Care Medicine, Logistic regression, law.invention, External validity, law, Anesthesiology, medicine, Humans, Intensive care unit, Mortality, business.industry, Retrospective cohort study, Odds ratio, Patient-to-intensivist ratio, Intensive Care Units, Emergency medicine, Cohort, Workforce, business
Abstract: Purpose The impact of intensivist workload on intensive care unit (ICU) outcomes is incompletely described and assessed across healthcare systems and countries. We sought to examine the association of patient-to-intensivist ratio (PIR) with hospital mortality in Australia/New Zealand (ANZ) ICUs. Methods We conducted a retrospective study of adult admissions to ANZ ICUs (August 2016–June 2018) using two cohorts: “narrow”, based on previously used criteria including restriction to ICUs with a single daytime intensivist; and “broad”, refined by individual ICU daytime staffing information. The exposure was average daily PIR and the outcome was hospital mortality. We used summary statistics to describe both cohorts and multilevel multivariable logistic regression models to assess the association of PIR with mortality. In each, PIR was modeled using restricted cubic splines to allow for non-linear associations. The broad cohort model included non-PIR physician and non-physician staffing covariables. Results The narrow cohort of 27,380 patients across 67 ICUs (predicted mortality: median 1.2% [IQR 0.4–1.4%]; mean 5.9% [sd 13.2%]) had a median PIR of 10.1 (IQR 7–14). The broad cohort of 91,206 patients across 73 ICUs (predicted mortality: 1.9% [0.6–6.5%]; 7.6% [14.9%]) had a median PIR of 7.8 (IQR 5.8–10.2). We found no association of PIR with mortality in either the narrow (PIR 1st spline term odds ratio [95% CI]: 1 [0.94, 1.06], Wald testing of spline terms p = 0.61) or the broad (1.02 [0.97, 1.07], p = 0.4) cohort. Conclusion We found no association of PIR with hospital mortality across ANZ ICUs. The low cohort predicted mortality may limit external validity. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06575-z.
Published: 2021

31. What Affects Adoption of Specialty Palliative Care in Intensive Care Units: A Qualitative Study

Author: Douglas B. White, Laura Fonseca, R. Sean Morrison, Hannah Wunsch, Robert E. Fullilove, and May Hua
Subjects: Palliative care, Critical Illness, Specialty, Context (language use), Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Nursing, law, Intensive care, Humans, Medicine, 030212 general & internal medicine, Qualitative Research, General Nursing, business.industry, Palliative Care, Intensive care unit, 3. Good health, Intensive Care Units, Anesthesiology and Pain Medicine, Conceptual framework, 030220 oncology & carcinogenesis, Hospice and Palliative Care Nursing, Critical illness, Neurology (clinical), business, Qualitative research
Abstract: Context Although many patients with critical illness may benefit from involvement of palliative care specialists, adoption of these services in the intensive care unit (ICU) is variable. Objective To characterize reasons for variable buy-in for specialty palliative care in the ICU, and identify factors associated with routine involvement of specialists in appropriate cases. Methods Qualitative study using in-depth, semi-structured interviews with ICU attendings, nurses, and palliative care clinicians, purposively sampled from eight ICUs (medical, surgical, cardiothoracic, neurological) with variable use of palliative care services within two urban, academic medical centers. Interviews were transcribed and coded using an iterative and inductive approach with constant comparison. Results We identified three types of specialty palliative care adoption in ICUs, representing different phases of buy-in. The “nascent” phase was characterized by the need for education about palliative care services and clarification of which patients may be appropriate for involvement. During the key “transitional” phase, use of specialists depended on development of “comfort and trust”, which centered on four aspects of the ICU-palliative care clinician relationship: 1) increasing familiarity between clinicians; 2) navigating shared responsibility with primary clinicians; 3) having a collaborative approach to care; and 4) having successful experiences. In the “mature” phase, ICU and palliative care clinicians worked to strengthen their existing collaboration, but further adoption was limited by the availability and resources of the palliative care team. Conclusion This conceptual framework identifying distinct phases of adoption may assist institutions aiming to foster sustained adoption of specialty palliative care in an ICU setting.
Published: 2021
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32. Practice Patterns in the Initiation of Secondary Vasopressors and Adjunctive Corticosteroids during Septic Shock in the United States

Author: Bijan Teja, Hannah Wunsch, Nicholas A Bosch, and Allan J. Walkey
Subjects: Pulmonary and Respiratory Medicine, endocrine system, Vasopressin, law.invention, Norepinephrine (medication), Norepinephrine, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, law, medicine, Humans, Vasoconstrictor Agents, 030212 general & internal medicine, Hydrocortisone, Practice patterns, business.industry, Septic shock, Editorials, medicine.disease, Shock, Septic, Intensive care unit, United States, Intensive Care Units, 030228 respiratory system, Methylprednisolone, Anesthesia, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: Rationale: A central component of septic shock treatment is the infusion of vasopressors, most commonly starting with norepinephrine. However, the optimal approach and practice patterns to initiati...
Published: 2021
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33. The association between opioid prescribing and opioid-related mortality within neighborhoods in Ontario, Canada: a case control study

Author: Karim S. Ladha, Duminda N. Wijeysundera, Hannah Wunsch, Hance Clarke, Calvin Diep, Naheed Jivraj, Diana Martins, Hannah Chung, Karanpreet Bath, and Tara Gomes
Subjects: Psychiatry and Mental health, Health (social science), Toxicology
Published: 2022
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34. The incidence of postoperative vasopressor usage, a prospective international observational study: ‘SQUEEZE’

Author: Ben Creagh-Brown, Hannah Wunsch, Peter Martin, Pierre Harlem, Lui Forni, S. Ramani Moonesinghe, and Ib Jammer
Abstract: Background: Postoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilatation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilatation. The incidence of postoperative vasopressors and outcomes associated with their use has never been described. We hypothesise that there is variation across centres in using vasopressors after surgery. There may also be a variation in the incidence of organ dysfunction, organ support use, and clinical outcomes in patients treated with postoperative vasopressor therapy. Method: The primary objective of this study is to determine what proportion of patients receive postoperative vasopressor infusions. We will identify factors in variation of care (patient, condition, surgery, and intraoperative management) associated with the receipt of postoperative vasopressor infusions. We will also assess the incidence of associated organ dysfunction and clinical outcomes among those who receive vasopressors. This will be accomplished with a prospective, international, multicentre cohort study that includes all adult (≥18 years) non-cardiac surgical patients in participating centres. Patients undergoing cardiac, obstetric or day-case surgery will be excluded. We will recruit two cohorts of patients: Cohort A will include all eligible patients admitted to participating hospitals for seven consecutive days. Cohort B will include 30 sequential patients per hospital, with the single additional inclusion criterion of postoperative vasopressor usage. We expect to collect data on approximately 40,000 patients for cohort A and 12,800 patients for cohort B. Discussion: While in cardiac surgery, clinical trials have informed the choice of vasopressors used to treat postoperative vasoplegia, there remains equipoise over the best approach in non-cardiac surgery. Our study will represent the first large-scale assessment of the use of vasopressors after non-cardiac surgery. These data will inform future studies, including trials of different vasopressors and potential management options to improve outcomes and reduce resource use after surgery. Trial registration: ClinicalTrials.gov Identifier: NCT03805230, 15th January 2019
Published: 2022
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35. New and Persistent Sedative Prescriptions Among Older Adults After Critical Illness: A Population-Based Cohort Study

Author: Lisa D, Burry, Chaim M, Bell, Andrea, Hill, Ruxandra, Pinto, Damon C, Scales, Susan E, Bronskill, David, Williamson, Louise, Rose, Longdi, Fu, Robert, Fowler, Claudio M, Martin, Lisa, Dolovich, and Hannah, Wunsch
Abstract: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use post-hospitalization.For sedative-naïve older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt?Population-based cohort study of ICU survivors ≥66 years who had not filled sedative prescriptions ≤6 months pre-hospitalization (sedative-naïve) in Ontario, Canada (2003 - 2019). Using multilevel logistic regression, we described demographic, clinical, and hospital characteristics and their association with new sedative prescription ≤7 days of discharge. We quantified variation between hospitals using the adjusted median odds ratio (aMOR). Factors associated with persistent prescriptions (≤6 months) were examined with multivariable proportional hazards model.250,428 patients were included (mean age 76, 61% male). 15,277 (6.1%) filled a new sedative prescription with variation across hospitals (2% (95% CI 1-3) to 44% (3-57)); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (aOR 4.00, 3.72-4.31); receipt of inpatient geriatric (aOR 1.95, 1.80-2.10) or psychiatry (aOR 2.76, 2.62-2.91) consultation, invasive ventilation (aOR 1.59, 1.53-1.66), and ICU length of stay ≥7 days (aOR 1.50, 1.42-1.58). The residual heterogeneity between hospitals (aMOR 1.43, 1.35-1.49) had a stronger association with new sedative prescriptions than Charlson comorbidity score or sepsis. Factors associated with persistent sedative use were similar with the addition of females (sHR 1.07, 1.02-1.13) and pre-existing polypharmacy (sHR 0.88, 0.80-0.93).One in 15 sedative-naïve older adult ICU survivors filled a new sedative ≤7 days of discharge, of whom more than half filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation.
Published: 2022

36. Renin-Angiotensin System Inhibitors and Major Cardiovascular Events after Sepsis

Author: Federico Angriman, Laura C. Rosella, Patrick R. Lawler, Dennis T. Ko, Claudio M. Martin, Hannah Wunsch, and Damon C. Scales
Subjects: Pulmonary and Respiratory Medicine
Abstract: Adult sepsis survivors have an increased risk of experiencing long-term cardiovascular events.To determine whether the cardiovascular risk following sepsis is mitigated by renin-angiotensin system inhibitors (RASi).Population-based cohort study of adult sepsis survivors designed to emulate a target randomized trial with an active comparator and new-user design. We excluded patients with a first-line indication for prescription of RASi (e.g., coronary heart disease, heart failure, chronic kidney disease, and hypertension with diabetes mellitus). The main exposure of interest was a new prescription of a RASi within 30 days of hospital discharge. The active comparator was a new prescription of either a calcium channel blocker or a thiazide diuretic, also within 30 days of hospital discharge. The primary outcome of interest was the composite of myocardial infarction, stroke, and all-cause mortality during follow-up to 5 years. We used inverse probability weighting of a Cox proportional hazards model and reported results using hazards ratios (HR) with 95% confidence intervals (CI).The cohort included 7,174 adult sepsis survivors, of whom 3,805 were new users of a RASi and 3,369 were new users of a calcium channel blocker or a thiazide diuretic. New users of a RASi experienced a lower hazard of major cardiovascular events compared to new users of a calcium channel blocker or a thiazide diuretic (HR 0.93, 95% CI 0.87 - 0.99). This association was consistent across different follow-up intervals and multiple sensitivity analyses.A new RASi prescription is associated with a reduction in major cardiovascular events after sepsis. A randomized controlled trial should be considered to confirm this finding.
Published: 2022

37. Critical illness in patients with hematologic malignancy: a population-based cohort study

Author: Vikas Gupta, Santhosh Thyagu, Hannah Wunsch, Matthew C. Cheung, Refik Saskin, Bruno L. Ferreyro, Laveena Munshi, and Damon C. Scales
Subjects: Mechanical ventilation, education.field_of_study, medicine.medical_specialty, business.industry, Anemia, Incidence (epidemiology), medicine.medical_treatment, Population, Critical Care and Intensive Care Medicine, medicine.disease, Intensive care unit, Confidence interval, law.invention, law, Anesthesiology, Internal medicine, medicine, education, business, Cohort study
Abstract: To describe the modern incidence and predictors of ICU admission for adult patients newly diagnosed with a hematologic malignancy. We conducted a population-based cohort study of adults with a new diagnosis of hematologic malignancy (April 1, 2006–March 31, 2017) in Ontario, Canada. We described the baseline demographic, clinical and laboratory predictors of ICU admission and subsequent mortality. The primary outcome was the incidence of ICU admission within 1 year of hematologic malignancy diagnosis. We assessed the predictors of ICU admission using Cox-proportional models that accounted for the competing risk of death and reported as subdistribution hazard ratios (sHR) with 95% confidence intervals (CI). A total of 87,965 patients (mean [SD] age, 67.8 (15.7) years) were included. The 1-year incidence of ICU admission was 13.9% (median time 35 days), ranging from 7.3% (indolent lymphoma) to 22.5% (acute myeloid leukemia). After multivariable adjustment, compared to indolent lymphoma, acute myeloid leukemia (sHR, 3.09; 95% CI 2.84–3.35), aggressive non-Hodgkin lymphoma (sHR, 2.47; 95% CI 2.31–2.65) and acute lymphoblastic leukemia (sHR, 2.46; 95% CI 2.15–2.80) had the highest risk of ICU admission. Comorbidities such as cardiovascular disease (sHR, 2.09; 95% CI 2.01–2.19), chronic obstructive pulmonary disease (sHR, 1.33; 95% CI 1.26–1.39) and baseline laboratory abnormalities (anemia, thrombocytopenia and high creatinine) were also associated with ICU admission. Among ICU patients, 36.7% required invasive mechanical ventilation and in-hospital mortality was 31%. Critical illness in patients with a newly diagnosed hematologic malignancy is frequent, occurring early after diagnosis. Certain baseline characteristics can help identify those patients at the highest risk.
Published: 2021
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38. History of Critical Care Medicine

Author: Hannah Wunsch
Subjects: General Medicine, Critical Care and Intensive Care Medicine
Published: 2023
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39. Attention to Immortal Time Bias in Critical Care Research

Author: Hannah Wunsch, Allan J. Walkey, Hayley B. Gershengorn, and Emily A. Vail
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Critical Care, Care perspective, Comparative effectiveness research, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Bias, Randomized controlled trial, law, Intervention (counseling), Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, business.industry, Ascorbic acid, Checklist, Harm, 030228 respiratory system, Research Design, Observational study, Health Services Research, business
Abstract: Observational studies in critical care medicine offer a popular and practical approach to questions of treatment effectiveness. Although observational research is widely understood to be susceptible to design and interpretation challenges, one well-described source of bias-immortal time bias (ITB)-is frequently present yet often overlooked. ITB may be introduced by study design oversights or mishandled during data analysis. When present, ITB can create inappropriate estimates of the benefit or harm of an exposure or intervention. Studies examining treatments in critically ill patients may be particularly susceptible to ITB, with consequences for clinical adoption and design and initiation of randomized trials. In this Critical Care Perspective, we illustrate the persistent problem of ITB in observational research using recent studies of hydrocortisone, ascorbic acid, and thiamine therapy in patients with sepsis and septic shock. Of the eight studies examined, none contained enough design or reporting elements to rule out the presence of ITB. To mitigate the influence of ITB in future observational studies, we present a novel checklist to help readers assess the features of study design, analysis, and reporting that introduce ITB or obscure its presence. We recommend that commonly used tools designed to evaluate observational research studies should include an ITB assessment.
Published: 2021
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40. Frailty and long-term outcomes following critical illness: A population-level cohort study

Author: Robert A. Fowler, Hannah Wunsch, Damon C. Scales, Andrea D. Hill, and Ruxandra Pinto
Subjects: medicine.medical_specialty, Population level, Critical Illness, Frail Elderly, Critical Care and Intensive Care Medicine, Patient Readmission, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Long term outcomes, Humans, Aged, Retrospective Studies, Hospital readmission, Frailty, Proportional hazards model, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, 3. Good health, Icu admission, 030228 respiratory system, Critical illness, business, Cohort study
Abstract: Purpose To provide population-level estimates of the association of frailty with one-year outcomes after critical illness. Materials and methods Retrospective cohort study of patients who survived an ICU admission between April 2002 and March 2015. Pre-existing frailty was classified using the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable Cox regression and Fine and Gray models were used to examine the association between frailty and mortality and hospital readmission. Results Of 534,991 patients, 19.3% had pre-existing frailty. Compared to non-frail survivors, at one-year frail patients had higher mortality (18.3% vs 9.5%, adjusted HR 1.17 95% CI: 1.15–1.19) and hospital readmission (44.4% vs 36.6%, adjusted HR 1.10 95% CI: 1.08–1.11) and a CAN$19,628 (95% CI: $19,279–$19,997) greater increase in healthcare costs compared to the year prior to hospitalization. The association between frailty and mortality was stronger among older individuals, but the risk of readmission among frail patients decreased with age. Conclusion Patients with pre-existing frailty who develop critical illness have higher rates of hospital readmission and death than patients without frailty, and age modifies these associations. These data highlight the importance of considering both frailty and age when seeking to identify at-risk patients who might benefit from closer follow-up after discharge.
Published: 2021
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41. Administrative Data Is Insufficient to Identify Near-Future Critical Illness: A Population-Based Retrospective Cohort Study

Author: Allan Garland, Ruth Ann Marrie, Hannah Wunsch, Marina Yogendran, and Daniel Chateau
Abstract: BackgroundPrediction of future critical illness could render it practical to test interventions seeking to avoid or delay the coming event.ObjectiveIdentify adults having >33% probability of near-future critical illness.Research DesignRetrospective cohort study, 2013–2015.SubjectsCommunity-dwelling residents of Manitoba, Canada, aged 40–89 years.MeasuresThe outcome was a near-future critical illness, defined as intensive care unit admission with invasive mechanical ventilation, or non-palliative death occurring 30–180 days after 1 April each year. By dividing the data into training and test cohorts, a Classification and Regression Tree analysis was used to identify subgroups with ≥33% probability of the outcome. We considered 72 predictors including sociodemographics, chronic conditions, frailty, and health care utilization. Sensitivity analysis used logistic regression methods.ResultsApproximately 0.38% of each yearly cohort experienced near-future critical illness. The optimal Tree identified 2,644 mutually exclusive subgroups. Socioeconomic status was the most influential variable, followed by nursing home residency and frailty; age was sixth. In the training data, the model performed well; 41 subgroups containing 493 subjects had ≥33% members who developed the outcome. However, in the test data, those subgroups contained 429 individuals, with 20 (4.7%) experiencing the outcome, which comprised 0.98% of all subjects with the outcome. While logistic regression showed less model overfitting, it likewise failed to achieve the stated objective.ConclusionsHigh-fidelity prediction of near-future critical illness among community-dwelling adults was not successful using population-based administrative data. Additional research is needed to ascertain whether the inclusion of additional types of data can achieve this goal.
Published: 2022
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42. Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?

Author: Daniel Brodie, Darryl Abrams, Jeremy R. Beitler, Gordon D. Rubenfeld, Ewan C. Goligher, Purnema Madahar, Robert A. Fowler, May Hua, George Tomlinson, Gavin D. Perkins, Laveena Munshi, Eddy Fan, Niall D. Ferguson, Matthew R. Baldwin, Arthur S. Slutsky, Daniel F. McAuley, Hannah Wunsch, and Christopher J. Yarnell
Subjects: Pulmonary and Respiratory Medicine, Critical Care, Clinical Decision-Making, Bayesian probability, Psychological intervention, MEDLINE, Article, 03 medical and health sciences, 0302 clinical medicine, Frequentist inference, Prior probability, Humans, Medicine, 030212 general & internal medicine, Probability, Clinical Trials as Topic, Actuarial science, business.industry, Interpretation (philosophy), Bayes Theorem, Clinical trial, Harm, 030228 respiratory system, Research Design, RB, business
Abstract: Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness. In the majority of cases, Bayesian and frequentist analyses agreed. In the remainder, Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance, where interpretation depended substantially on choice of prior distribution, and where benefit was improbable despite statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.
Published: 2021
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43. Informing Healthcare Decisions with Observational Research Assessing Causal Effect. An Official American Thoracic Society Research Statement

Author: Therese A. Stukel, Nicolas Roche, Andrea S. Gershon, Noah C. Schoenberg, Min J. Joo, Kevin J. Anstrom, Anuj B. Mehta, Bruce G. Bender, Kristin A. Riekert, Valery Lavergne, David H. Au, Mohsen Sadatsafavi, Allan J. Walkey, Kevin C. Wilson, Hannah Wunsch, Marc Miravitlles, Peter K. Lindenauer, Richard A. Mularski, Joel J. Africk, Raed A. Dweik, Eyal Oren, MeiLan K. Han, Curtis H. Weiss, Jerry A. Krishnan, M. Alan Brookhart, and Louise Rose
Subjects: Pulmonary and Respiratory Medicine, Biomedical Research, Critical Care, Clinical Decision-Making, Critical Care and Intensive Care Medicine, Thoracic Diseases, Health care, Correspondence, Medicine, Humans, observational studies, Societies, Medical, American Thoracic Society Documents, Medical education, Evidence-Based Medicine, practice guidelines, business.industry, Causal effect, evidence synthesis, Research statement, Guideline, United States, Clinical Practice, Observational Studies as Topic, Practice Guidelines as Topic, Observational study, business, Delivery of Health Care, Evidence synthesis
Abstract: Rationale: Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guidelines, decisions, and policy. Objectives: The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement to clarify the role of observational studies—alongside randomized controlled trials (RCTs)—in informing clinical decisions in pulmonary, critical care, and sleep medicine. Methods: The committee examined the strengths of observational studies assessing causal effects, how they complement RCTs, factors that impact observational study quality, perceptions of observational research, and, finally, the practicalities of incorporating observational research into ATS clinical practice guidelines. Measurements and Main Results: There are strengths and weakness of observational studies as well as RCTs. Observational studies can provide evidence in representative and diverse patient populations. Quality observational studies should be sought in the development of ATS clinical practice guidelines, and medical decision-making in general, when 1) no RCTs are identified or RCTs are appraised as being of low- or very low-quality (replacement); 2) RCTs are of moderate quality because of indirectness, imprecision, or inconsistency, and observational studies mitigate the reason that RCT evidence was downgraded (complementary); or 3) RCTs do not provide evidence for outcomes that a guideline committee considers essential for decision-making (e.g., rare or long-term outcomes; “sequential”). Conclusions: Observational studies should be considered in developing clinical practice guidelines and in making clinical decisions.
Published: 2021

44. Use of Hydrocortisone, Ascorbic Acid, and Thiamine in Adults with Septic Shock

Author: Allan J. Walkey, Ruxandra Pinto, Nicholas A Bosch, Hannah Wunsch, Peter K. Lindenauer, Emily A. Vail, and Hayley B. Gershengorn
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Septic shock, business.industry, Critical Care and Intensive Care Medicine, medicine.disease, Ascorbic acid, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, Thiamine, 030212 general & internal medicine, business, Severe sepsis, Hydrocortisone, medicine.drug
Abstract: Rationale: In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, ...
Published: 2020
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45. Journal-related Activities and Other Special Activities at the 2020 American Society of Anesthesiologists Meeting

Author: Martin J. London, Jerrold H. Levy, Hannah Wunsch, Michael J. Avram, Deborah J. Culley, Evan D. Kharasch, and Daniel I. Sessler
Subjects: medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Family medicine, MEDLINE, Medicine, business, American society of anesthesiologists
Published: 2020
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46. Mechanical Ventilation in COVID-19: Interpreting the Current Epidemiology

Author: Hannah Wunsch
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Decision-Making, Pneumonia, Viral, Critical Care and Intensive Care Medicine, Betacoronavirus, Risk Factors, Epidemiology, medicine, Humans, Viral therapy, Intensive care medicine, Pandemics, Mechanical ventilation, SARS-CoV-2, Extramural, business.industry, Editorials, COVID-19, Respiration, Artificial, Current (fluid), Coronavirus Infections, Intubation, business
Published: 2020
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47. Vasopressor Dosing in Septic Shock Clinical Trials: A Systematic Review and Ecologic Study

Author: Ruxandra Pinto, Bijan Teja, Nicholas A Bosch, Allan J. Walkey, and Hannah Wunsch
Subjects: Pulmonary and Respiratory Medicine, Clinical Trials as Topic, medicine.medical_specialty, Dose-Response Relationship, Drug, Ecology, business.industry, Septic shock, Patient Selection, MEDLINE, Ecological study, Blood Pressure, Prognosis, medicine.disease, Shock, Septic, Clinical trial, Humans, Vasoconstrictor Agents, Medicine, Dosing, business, Intensive care medicine
Published: 2020
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48. Persistent Postoperative Opioid Use

Author: Mark D. Neuman, Jennifer Bethell, Duminda N. Wijeysundera, Faizal Raghavji, Brian T. Bateman, Hannah Wunsch, Naheed Jivraj, and Karim S. Ladha
Subjects: Pediatrics, medicine.medical_specialty, education.field_of_study, business.industry, Incidence (epidemiology), Population, MEDLINE, Opioid use disorder, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Cohort, medicine, Observational study, 030212 general & internal medicine, Adverse effect, education, business, Cohort study
Abstract: BackgroundWhile persistent opioid use after surgery has been the subject of a large number of studies, it is unknown how much variability in the definition of persistent use impacts the reported incidence across studies. The objective was to evaluate the incidence of persistent use estimated with different definitions using a single cohort of postoperative patients, as well as the ability of each definition to identify patients with opioid-related adverse events.MethodsThe literature was reviewed to identify observational studies that evaluated persistent opioid use among opioid-naive patients requiring surgery, and any definitions of persistent opioid use were extracted. Next, the authors performed a population-based cohort study of opioid-naive adults undergoing 1 of 18 surgical procedures from 2013 to 2017 in Ontario, Canada. The primary outcome was the incidence of persistent opioid use, defined by each extracted definition of persistent opioid use. The authors also assessed the sensitivity and specificity of each definition to identify patients with an opioid-related adverse event in the year after surgery.ResultsTwenty-nine different definitions of persistent opioid use were identified from 39 studies. Applying the different definitions to a cohort of 162,830 opioid-naive surgical patients, the incidence of persistent opioid use in the year after surgery ranged from 0.01% (n = 10) to 14.7% (n = 23,442), with a median of 0.7% (n = 1,061). Opioid-related overdose or diagnosis associated with opioid use disorder in the year of follow-up occurred in 164 patients (1 per 1,000 operations). The sensitivity of each definition to identify patients with the composite measure of opioid use disorder or opioid-related toxicity ranged from 0.01 to 0.36, while specificity ranged from 0.86 to 1.00.ConclusionsThe incidence of persistent opioid use reported after surgery varies more than 100-fold depending on the definition used. Definitions varied markedly in their sensitivity for identifying adverse opioid-related event, with low sensitivity overall across measures.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New
Published: 2020
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49. First-Line Vasopressor Use in Septic Shock and Route of Administration: An Epidemiologic Study

Author: Bijan Teja, Nicholas A. Bosch, Duminda N. Wijeysundera, Harindra C. Wijeysundera, Refik Saskin, Andrea D. Hill, Henry T. Stelfox, Allan J. Walkey, and Hannah Wunsch
Subjects: Pulmonary and Respiratory Medicine, Cohort Studies, Norepinephrine, Humans, Vasoconstrictor Agents, Shock, Septic, Alberta, Retrospective Studies
Published: 2022

50. The physiological underpinnings of life-saving respiratory support

Author: Irene Telias, Laurent J. Brochard, Simone Gattarello, Hannah Wunsch, Detajin Junhasavasdikul, Karen J. Bosma, Luigi Camporota, Daniel Brodie, John J. Marini, Arthur S. Slutsky, and Luciano Gattinoni
Subjects: Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation, Ventilator-Induced Lung Injury, Iatrogenic Disease, Humans, Critical Care and Intensive Care Medicine, Respiratory Insufficiency, Respiration, Artificial
Abstract: Treatment of respiratory failure has improved dramatically since the polio epidemic in the 1950s with the use of invasive techniques for respiratory support: mechanical ventilation and extracorporeal respiratory support. However, respiratory support is only a supportive therapy, designed to "buy time" while the disease causing respiratory failure abates. It ensures viable gas exchange and prevents cardiorespiratory collapse in the context of excessive loads. Because the use of invasive modalities of respiratory support is also associated with substantial harm, it remains the responsibility of the clinician to minimize such hazards. Direct iatrogenic consequences of mechanical ventilation include the risk to the lung (ventilator-induced lung injury) and the diaphragm (ventilator-induced diaphragm dysfunction and other forms of myotrauma). Adverse consequences on hemodynamics can also be significant. Indirect consequences (e.g., immobilization, sleep disruption) can have devastating long-term effects. Increasing awareness and understanding of these mechanisms of injury has led to a change in the philosophy of care with a shift from aiming to normalize gases toward minimizing harm. Lung (and more recently also diaphragm) protective ventilation strategies include the use of extracorporeal respiratory support when the risk of ventilation becomes excessive. This review provides an overview of the historical background of respiratory support, pathophysiology of respiratory failure and rationale for respiratory support, iatrogenic consequences from mechanical ventilation, specifics of the implementation of mechanical ventilation, and role of extracorporeal respiratory support. It highlights the need for appropriate monitoring to estimate risks and to individualize ventilation and sedation to provide safe respiratory support to each patient.
Published: 2022

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