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1. Incorporating harms into the weighting of the revised Agency for Healthcare Research and Quality Patient Safety for Selected Indicators Composite (Patient Safety Indicator 90)

Author: Kathryn M McDonald, Sheryl M Davies, Halcyon G. Skinner, Patrick S Romano, Robert L. Houchens, Garth H. Utter, Patricia A Zrelak, and Pamela L Owens
Subjects: medicine.medical_specialty, Percentile, Average treatment effect, Methods Corner, Policy and Administration, 8.1 Organisation and delivery of services, Medicare, Patient safety, United States Agency for Healthcare Research and Quality, PSI 90, Clinical Research, Acute care, patient safety, Humans, Medicine, quality indicator, composite, Healthcare Cost and Utilization Project, Lung, Reliability (statistics), Quality Indicators, Health Care, Aged, AHRQ, business.industry, Health Policy, Reproducibility of Results, Health Services, United States, Health Care, Emergency medicine, Propensity score matching, Quality Indicators, Public Health and Health Services, Health Policy & Services, Patient Safety, Health Services Research, business, Medicaid, harm, Health and social care services research
Abstract: OBJECTIVE: To reweight the Agency for Healthcare Research and Quality Patient Safety for Selected Indicators Composite (Patient Safety Indicator [PSI] 90) from weights based solely on the frequency of component PSIs to those that incorporate excess harm reflecting patients' preferences for outcome‐related health states. DATA SOURCES: National administrative and claims data involving hospitalizations in nonfederal, nonrehabilitation, acute care hospitals. STUDY DESIGN: We estimated the average excess aggregate harm associated with the occurrence of each component PSI using a cohort sample for each indicator based on denominator‐eligible records. We used propensity scores to account for potential confounding in the risk models for each PSI and weighted observations to estimate the “average treatment effect in the treated” for those with the PSI event. We fit separate regression models for each harm outcome. Final PSI weights reflected both the disutilities and the frequencies of the harms. DATA COLLECTION/EXTRACTION METHODS: We estimated PSI frequencies from the 2012 Healthcare Cost and Utilization Project State Inpatient Databases with present on admission data and excess harms using 2012–2013 Centers for Medicare & Medicaid Services Medicare Fee‐for‐Service data. PRINCIPAL FINDINGS: Including harms in the weighting scheme changed individual component weights from the original frequency‐based weighting. In the reweighted composite, PSIs 11 (“Postoperative Respiratory Failure”), 13 (“Postoperative Sepsis”), and 12 (“Perioperative Pulmonary Embolism or Deep Vein Thrombosis”) contributed the greatest harm, with weights of 29.7%, 21.1%, and 20.4%, respectively. Regarding reliability, the overall average hospital signal‐to‐noise ratio for the reweighted PSI 90 was 0.7015. Regarding discrimination, among hospitals with greater than median volume, 34% had significantly better PSI 90 performance, and 41% had significantly worse performance than benchmark rates (based on percentiles). CONCLUSIONS: Reformulation of PSI 90 with harm‐based weights is feasible and results in satisfactory reliability and discrimination, with a more clinically meaningful distribution of component weights.
Published: 2022
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2. Investigation and management of postcoital bleeding

Author: Nicholas J Wood, Gemma L Owens, and Pierre L. Martin-Hirsch
Subjects: Cervical pathology, medicine.medical_specialty, business.industry, Postcoital bleeding, General surgery, medicine, Cancer, medicine.disease, business
Published: 2022
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3. Pathogenesis of obstructive sleep apnea in people living with HIV

Author: Jeremy E. Orr, Rebecca J. Theilmann, Charles B. Hicks, Chantal Darquenne, Pamela N. DeYoung, Sonia Jain, Maile Y. Karris, Robert L. Owens, Christopher N. Schmickl, Atul Malhotra, and Bradley A. Edwards
Subjects: medicine.medical_specialty, Sleep Apnea, Physiology, Polysomnography, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Medical and Health Sciences, Body Mass Index, Pathogenesis, stomatognathic system, Clinical Research, Physiology (medical), Internal medicine, Behavioral and Social Science, Humans, Medicine, Lung, obstructive sleep apnea, Sleep Apnea, Obstructive, Obstructive, business.industry, Prevention, HIV, Biological Sciences, Middle Aged, medicine.disease, nervous system diseases, respiratory tract diseases, Obstructive sleep apnea, Infectious Diseases, fatigue, Sleep Research, Sleep, business, Research Article
Abstract: Obstructive sleep apnea (OSA) is highly prevalent in people living with human immunodeficiency virus (HIV) (PLWH), and it might contribute to frequently reported symptoms and comorbidities. Traditional risk factors for OSA are often absent in PLWH, suggesting that HIV or HIV medications might predispose to OSA. Therefore, we measured the anatomical and nonanatomical traits important for OSA pathogenesis in those with and without HIV. We recruited virally suppressed PLWH who had been previously diagnosed with OSA (PLWH + OSA) adherent to positive airway pressure (PAP) therapy, along with age-, sex-, and body mass index (BMI)-matched OSA controls. All participants underwent a baseline polysomnogram to assess OSA severity and a second overnight research sleep study during which the airway pressure was adjusted slowly or rapidly to measure the OSA traits. Seventeen PLWH + OSA and 17 OSA control participants were studied [median age = 58 (IQR = 54–65) yr, BMI = 30.7 (28.4–31.8) kg/m(2), apnea-hypopnea index = 46 (24–74)/h]. The groups were similar, although PLWH + OSA demonstrated greater sleepiness (despite PAP) and worse sleep efficiency on baseline polysomnography. On physiological testing during sleep, there were no statistically significant differences in OSA traits (including V(eupnea), V(arousal), V(passive), V(active), and loop gain) between PLWH + OSA and OSA controls, using mixed-effects modeling to account for age, sex, and BMI and incorporating each repeated measurement (range = 72–334 measures/trait). Our data suggest that well-treated HIV does not substantially impact the pathogenesis of OSA. Given similar underlying physiology, existing available therapeutic approaches are likely to be adequate to manage OSA in PLWH, which might improve symptoms and comorbidities. NEW & NOTEWORTHY Clinical data suggest an increased risk of obstructive sleep apnea (OSA) in people living with HIV (PLWH), while OSA might account for chronic health issues in this population. We characterized the anatomical and nonanatomical OSA traits in PLWH + OSA compared with OSA controls, using detailed physiological measurements obtained during sleep. Our data suggest against a major impact of HIV on OSA pathogenesis. Available OSA management strategies should be effective to address this potentially important comorbidity in PLWH.
Published: 2021
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4. Sleep Outcomes From AWAKE-HF: A Randomized Clinical Trial of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction

Author: Kade Birkeland, Raj M. Khandwalla, Emmanuel Fombu, Steven R. Steinhubl, Jonas F. Dorn, J. Thomas Heywood, Daniel Grant, and Robert L. Owens
Subjects: medicine.medical_specialty, Central sleep apnea, Tetrazoles, Cheyne–Stokes respiration, Sacubitril, Angiotensin Receptor Antagonists, Enalapril, Internal medicine, medicine, Humans, Wakefulness, Heart Failure, business.industry, Aminobutyrates, Biphenyl Compounds, Stroke Volume, medicine.disease, Obstructive sleep apnea, Drug Combinations, Valsartan, Heart failure, Cardiology, medicine.symptom, Sleep, Cardiology and Cardiovascular Medicine, business, Sacubitril, Valsartan, medicine.drug
Abstract: Background Heart failure and sleep-disordered breathing have been increasingly recognized as co-occurring conditions. Their bidirectional relationship warrants investigation into whether heart failure therapy improves sleep and sleep-disordered breathing. We sought to explore the effect of treatment with sacubitril/valsartan on sleep-related endpoints from the AWAKE-HF study. Methods and Results AWAKE-HF was a randomized, double-blind study conducted in 23 centers in the United States. Study participants with heart failure with reduced rejection fraction and New York Heart Association class II or III symptoms were randomly assigned to receive treatment with either sacubitril/valsartan or enalapril. All endpoints were assessed at baseline and after 8 weeks of treatment. Portable sleep-monitoring equipment was used to measure the apnea-hypopnea index, including obstructive and central events. Total sleep time, wake after sleep onset and sleep efficiency were exploratory measures assessed using wrist actigraphy. The results were as follows 140 patients received treatment in the double-blind phase (sacubitril/valsartan, n = 70; enalapril, n = 70). At baseline, 39% and 40% of patients randomly assigned to receive sacubitril/valsartan or enalapril, respectively, presented with undiagnosed, untreated, moderate-to-severe sleep-disordered breathing (≥ 15 events/h), and nearly all had obstructive sleep apnea. After 8 weeks of treatment, the mean 4% apnea-hypopnea index changed minimally from 16.3/h to 15.2/h in the sacubitril/valsartan group and from 16.8/h to 17.6/h in the enalapril group. Mean total sleep time was long at baseline and decreased only slightly in both treatment groups at week 8 (–14 and –11 minutes for sacubitril/valsartan and enalapril, respectively), with small changes in wake after sleep onset and sleep efficiency in both groups. Conclusions In a cohort of patients with heart failure with reduced rejection fraction who met prescribing guidelines for sacubitril/valsartan, one-third had undiagnosed moderate-to-severe obstructive sleep apnea. The addition of sacubitril/valsartan therapy did not significantly improve sleep-disordered breathing or sleep duration or efficiency. Patients who meet indications for treatment with sacubitril/valsartan should be evaluated for sleep-disordered breathing.
Published: 2021
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5. Respiratory Therapists in an ICU Recovery Clinic: Two Institutional Experiences and Review of the Literature

Author: Alison Nestor, Amy L. Bellinghausen, Robert L. Owens, Frank Chu, Joseph Morrell, Brad W. Butcher, and Le Tm Ho
Subjects: Pulmonary and Respiratory Medicine, education.field_of_study, medicine.medical_specialty, ARDS, Mindfulness, business.industry, Population, Psychological intervention, Cognition, General Medicine, Critical Care and Intensive Care Medicine, medicine.disease, Mental health, Multidisciplinary approach, medicine, education, Intensive care medicine, business, Psychosocial
Abstract: Post-intensive care syndrome is an increasingly recognized complication of critical illness, with patients reporting new problems in physical, mental health and/or psychosocial, and cognitive function for months to years after their acute illness. As a way of diagnosing and treating post-intensive care syndrome, many centers around the world have established ICU recovery clinics, which take a multidisciplinary approach to care after the ICU. Dyspnea and pulmonary dysfunction are frequently encountered concerns in the post-ICU population. Despite this, few ICU recovery clinics have described how respiratory therapists (RTs) can contribute to treating these symptoms. We reviewed the literature with regard to the roles of an RT in post-ICU follow-up, described our institutional experiences with having RTs as part of our ICU recovery clinics, and identified additional ways that RTs might contribute to a post-intensive care syndrome diagnosis and treatment. Although RTs can provide invaluable experience and contributions to an ICU recovery clinic, there are few articles in the published literature on the ways in which this can be accomplished. We, therefore, provide analogies to other multidisciplinary clinic models as well as our own experiences. Future studies should focus on examining the impact of respiratory therapy diagnostic testing and interventions in the ICU recovery clinic on both patient and provider outcomes.
Published: 2021
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6. Optimal NIV Medicare Access Promotion: Patients With COPD

Author: Nicholas S. Hill, Gerard J. Criner, Richard D. Branson, Bartolome R. Celli, Neil R. MacIntyre, Amen Sergew, Peter C. Gay, Robert L. Owens, Lisa F. Wolfe, Joshua O. Benditt, Loutfi S. Aboussouan, John M. Coleman, Dean R. Hess, Timothy I. Morgenthaler, Atul Malhotra, Richard B. Berry, Karin G. Johnson, Marc I. Raphaelson, Babak Mokhlesi, Christine H. Won, Bernardo J. Selim, Barry J. Make, Bernie Y. Sunwoo, Nancy A. Collop, Susheel P. Patil, Alejandro D. Chediak, Eric J. Olson, and Kunwar Praveen Vohra
Subjects: Pulmonary and Respiratory Medicine, Obesity hypoventilation syndrome, medicine.medical_specialty, Central sleep apnea, business.industry, medicine.medical_treatment, Sleep apnea, Critical Care and Intensive Care Medicine, medicine.disease, Sleep medicine, Apnea–hypopnea index, Oxygen therapy, Positive airway pressure, medicine, Continuous positive airway pressure, Cardiology and Cardiovascular Medicine, business, Intensive care medicine
Abstract: This document summarizes suggestions of the central sleep apnea (CSA) Technical Expert Panel working group. This paper shares our vision for bringing the right device to the right patient at the right time. For patients with CSA, current coverage criteria do not align with guideline treatment recommendations. For example, CPAP and oxygen therapy are recommended but not covered for CSA. On the other hand, bilevel positive airway pressure (BPAP) without a backup rate may be a covered therapy for OSA, but it may worsen CSA. Narrow coverage criteria that require near elimination of obstructive breathing events on CPAP or BPAP in the spontaneous mode, even if at poorly tolerated pressure levels, may preclude therapy with BPAP with backup rate or adaptive servoventilation, even when those devices provide demonstrably better therapy. CSA is a dynamic disorder that may require different treatments over time, sometimes switching from one device to another; an example is switching from BPAP with backup rate to an adaptive servoventilation with automatic end-expiratory pressure adjustments, which may not be covered. To address these challenges, we suggest several changes to the coverage determinations, including: (1) a single simplified initial and continuing coverage definition of CSA that aligns with OSA; (2) removal of hypoventilation terminology from coverage criteria for CSA; (3) all effective therapies for CSA should be covered, including oxygen and all PAP devices with or without backup rates or servo-mechanisms; and (4) patients shown to have a suboptimal response to one PAP device should be allowed to add oxygen or change to another PAP device with different capabilities if shown to be effective with testing.
Published: 2021
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7. Optimal NIV Medicare Access Promotion: Patients With Hypoventilation Syndromes

Author: Babak Mokhlesi, Christine H. Won, Barry J. Make, Bernardo J. Selim, Bernie Y. Sunwoo, Peter C. Gay, Robert L. Owens, Lisa F. Wolfe, Joshua O. Benditt, Loutfi S. Aboussouan, John M. Coleman, Dean R. Hess, Nicholas S. Hill, Gerard J. Criner, Richard D. Branson, Bartolome R. Celli, Neil R. MacIntyre, Amen Sergew, Timothy I. Morgenthaler, Atul Malhotra, Richard B. Berry, Karin G. Johnson, Marc I. Raphaelson, Nancy A. Collop, Susheel P. Patil, Alejandro D. Chediak, Eric J. Olson, and Kunwar Praveen Vohra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Promotion (rank), Hypoventilation syndromes, business.industry, media_common.quotation_subject, medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, Intensive care medicine, business, media_common
Published: 2021
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8. Executive Summary

Author: Peter C. Gay, Robert L. Owens, Lisa F. Wolfe, Joshua O. Benditt, Loutfi S. Aboussouan, John M. Coleman, Dean R. Hess, Nicholas S. Hill, Gerard J. Criner, Richard D. Branson, Bartolome R. Celli, Neil R. MacIntyre, Amen Sergew, Timothy I. Morgenthaler, Atul Malhotra, Richard B. Berry, Karin G. Johnson, Marc I. Raphaelson, Babak Mokhlesi, Christine H. Won, Bernardo J. Selim, Barry J. Make, Bernie Y. Sunwoo, Nancy A. Collop, Susheel P. Patil, Alejandro D. Chediak, Eric J. Olson, and Kunwar Praveen Vohra
Subjects: Pulmonary and Respiratory Medicine, Obesity hypoventilation syndrome, medicine.medical_specialty, Executive summary, Central sleep apnea, business.industry, MEDLINE, Critical Care and Intensive Care Medicine, medicine.disease, Sleep medicine, Scientific evidence, Family medicine, Positive airway pressure, medicine, Cardiology and Cardiovascular Medicine, business, Respiratory care
Abstract: The current national coverage determinations (NCDs) for noninvasive ventilation for patients with thoracic restrictive disorders, COPD, and hypoventilation syndromes were formulated in 1998. New original research, updated formal practice guidelines, and current consensus expert opinion have accrued that are in conflict with the existing NCDs. Some inconsistencies in the NCDs have been noted, and the diagnostic and therapeutic technology has also advanced in the last quarter century. Thus, these and related NCDs relevant to bilevel positive airway pressure for the treatment of OSA and central sleep apnea need to be updated to ensure the optimal health of patients with these disorders. To that end, the American College of Chest Physicians organized a multisociety (American Thoracic Society, American Academy of Sleep Medicine, and American Association for Respiratory Care) effort to engage experts in the field to: (1) identify current barriers to optimal care; (2) highlight compelling scientific evidence that would justify changes from current policies incorporating best evidence and practice; and (3) propose suggestions that would form the basis for a revised NCD in each of these 5 areas (thoracic restrictive disorders, COPD, hypoventilation syndromes, OSA, and central sleep apnea). The expert panel met during a 2-day virtual summit in October 2020 and subsequently crafted written documents designed to achieve provision of "the right device to the right patient at the right time." These documents have been endorsed by the participating societies following peer review and publication in CHEST and will be used to inform efforts to revise the current NCDs.
Published: 2021
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9. Optimal NIV Medicare Access Promotion: Patients With Thoracic Restrictive Disorders

Author: Lisa F. Wolfe, Joshua O. Benditt, Loutfi Aboussouan, Dean R. Hess, John M. Coleman, Peter C. Gay, Robert L. Owens, Loutfi S. Aboussouan, Nicholas S. Hill, Gerard J. Criner, Richard D. Branson, Bartolome R. Celli, Neil R. MacIntyre, Amen Sergew, Timothy I. Morgenthaler, Atul Malhotra, Richard B. Berry, Karin G. Johnson, Marc I. Raphaelson, Babak Mokhlesi, Christine H. Won, Bernardo J. Selim, Barry J. Make, Bernie Y. Sunwoo, Nancy A. Collop, Susheel P. Patil, Alejandro D. Chediak, Eric J. Olson, and Kunwar Praveen Vohra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Promotion (rank), business.industry, media_common.quotation_subject, Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, business, Intensive care medicine, media_common
Published: 2021
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10. Optimal NIV Medicare Access Promotion: Patients With Central Sleep Apnea

Author: Timothy I. Morgenthaler, Atul Malhotra, Richard B. Berry, Karin G. Johnson, Marc Raphaelson, Peter C. Gay, Robert L. Owens, Lisa F. Wolfe, Joshua O. Benditt, Loutfi S. Aboussouan, John M. Coleman, Dean R. Hess, Nicholas S. Hill, Gerard J. Criner, Richard D. Branson, Bartolome R. Celli, Neil R. MacIntyre, Amen Sergew, Marc I. Raphaelson, Babak Mokhlesi, Christine H. Won, Bernardo J. Selim, Barry J. Make, Bernie Y. Sunwoo, Nancy A. Collop, Susheel P. Patil, Alejandro D. Chediak, Eric J. Olson, and Kunwar Praveen Vohra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Promotion (rank), Central sleep apnea, business.industry, media_common.quotation_subject, Emergency medicine, medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, business, medicine.disease, media_common
Published: 2021
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11. Service Workers’ Well-Being During COVID-19: A Strengths-Based Inclusive Theory of Work Perspective

Author: Blake A. Allan, Erika E. Meierding, and Rhea L. Owens
Subjects: Organizational Behavior and Human Resource Management, Coronavirus disease 2019 (COVID-19), business.industry, Perspective (graphical), Sample (statistics), Public relations, Work (electrical), Vocational education, Well-being, Positive psychology, Psychology, business, Tertiary sector of the economy, General Psychology, Applied Psychology
Abstract: This study tested the Strengths-Based Inclusive Theory of Work (S-BIT of Work), a vocational theory that emphasizes positive psychological and cultural factors, among a sample of service industry workers during COVID-19. Service industry workers ( N = 320) were recruited via social media sources across the United States, and structural equation modeling was used to examine the model. This model included privilege and COVID-19 impact as contextual variables; organizational support and workplace dignity as promotive workplace variables; hope, strengths use, adaptability, empowerment, and perceived COVID-19 threat as individual variables; and fulfilling work and psychological distress as outcome variables. Privilege and workplace dignity were identified as particularly important variables; results suggested privilege was positively associated with a promotive work context and negatively related to psychological distress. Additionally, the greater the amount of privilege and dignity the service industry workers experienced, the greater their positive individual characteristics were able to flourish.
Published: 2021
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12. Indigenous microbial surrogates in wastewater used to understand public health risk expressed in the Disability-Adjusted Life Year (DALY) metric

Author: Christopher E. L. Owens, Peter T. Cox, Paul Byleveld, Bayzidur Rahman, and Nicholas J. Osborne
Subjects: Microbiology (medical), medicine.medical_specialty, Wastewater, Environmental health, Public health, Public Health, Environmental and Occupational Health, medicine, Disability-adjusted life year, Business, Metric (unit), Applied Microbiology and Biotechnology, Microbiology, Indigenous
Abstract: In any wastewater recycling scheme, the protection of public health is of primary importance. In Australia, the public health requirements applying to the treatment of recycled water are stringent. They use the Disability-Adjusted Life Year (DALY) metric to set a level of negligible public health risk. The target maximum risk of 10–6 DALY per person per year has been adopted in Australian water recycling guidelines since 2006. A key benefit of the DALY approach is its ability to standardise the understanding of risk across disparate areas of public health. To address the key challenge of translating the results of monitoring of microorganisms in the recycled water into this quantitative public health metric, we have developed a novel method. This paper summarises an approach where microbial surrogate organisms indigenous to wastewater are used to measure the efficiency of water recycling treatment processes and estimate public health risk. An example of recent implementation in the Greater Sydney region of Australia is provided.
Published: 2021
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13. Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Author: Grace Champlin, Winfred C. Wang, Jeremie H. Estepp, Andrew M. Heitzer, Robert F. Davis, Kenneth I. Ataga, Jane S. Hankins, Curtis L. Owens, Guolian Kang, Scott N. Hwang, Allison A. King, Lisa M. Jacola, Juan Ding, and Justin Newman
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Ultrasonography, Doppler, Transcranial, Anemia, Sickle Cell, General Biochemistry, Genetics and Molecular Biology, Central nervous system disease, Blood Transfusion, Autologous, Young Adult, Silent cerebral infarct, Antisickling Agents, Central Nervous System Diseases, Risk Factors, Internal medicine, Humans, Hydroxyurea, Medicine, Young adult, Cerebral infarcts, Stroke, Original Research, business.industry, Brain, Cerebral Infarction, medicine.disease, Sickle cell anemia, Disease Progression, Cardiology, Brain lesions, Female, Erythrocyte Transfusion, business, Magnetic Resonance Angiography
Abstract: Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ0thalassemia), exposed to chronic transfusions ( n = 12) or hydroxyurea ( n = 32), median age 19.2 years (range 18.0–31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5–54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0–15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76–0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2–64), abnormal pediatric exam ( P = 0.00084), and elevated transcranial Doppler ultrasound velocities ( P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.
Published: 2021
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14. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin 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Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, 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Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, 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Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A 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C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021
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15. A Case of a Rare Malignant Mixed Ovarian Germ Cell Tumor Masquerading as an Ectopic Pregnancy

Author: Ria Marwaha, Gemma L Owens, Helen F. Stringfellow, Panagiotis Giamougiannis, Antonios Anagnostopoulos, and Raj Naik
Subjects: Gynecology, endocrine system, Chemotherapy, medicine.medical_specialty, Ectopic pregnancy, Ovarian germ cell tumor, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Ovary, medicine.disease, Adnexal mass, medicine.anatomical_structure, medicine, Germ cell tumors, Presentation (obstetrics), business, Laparoscopy
Abstract: Malignant ovarian germ cell tumors (MOGCTs) are rare but disproportionately affect young women and adolescent girls. Although clinical presentation varies, these tumors can present with an adnexal mass and raised serum beta-human chorionic gonadotrophin (beta-hCG), mimicking an ectopic pregnancy. We present the case of a 20-year-old nulliparous woman, who was initially treated both medically and surgically as an ectopic pregnancy, and was eventually diagnosed with a malignant mixed germ cell tumor (MMGCT) following laparoscopy. We highlight the diagnostic challenges of ectopic pregnancies versus MOGCTs, and the importance of adopting a fertility-sparing approach in young nulliparous women. J Clin Gynecol Obstet. 2021;10(2):55-58 doi: https://doi.org/10.14740/jcgo743
Published: 2021
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16. Long-Term Domiciliary Noninvasive Ventilation for COPD

Author: Robert L. Owens
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Respiratory rate, Critical Care and Intensive Care Medicine, Hypoxemia, Hypercapnia, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Quality of life, medicine, Humans, Intensive care medicine, COPD, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, General Medicine, medicine.disease, Obstructive sleep apnea, 030228 respiratory system, Quality of Life, Breathing, Noninvasive ventilation, medicine.symptom, business
Abstract: COPD can lead to abnormalities in oxygenation as well as ventilation. Thanks to pioneering work by Dr Thomas Petty, supplemental oxygen therapy has been shown to improve morbidity and mortality for individuals with COPD and severe daytime hypoxemia. However, efforts to augment ventilation have been less uniformly successful. Recent studies employing a so-called high-intensity noninvasive ventilation strategy, which used high inspiratory pressures and backup breathing frequency to reduce arterial carbon dioxide levels, have shown improved quality of life and reduced mortality. Thus, efforts are underway to better identify and treat patients with COPD who might benefit from noninvasive ventilation, though many practical questions remain.
Published: 2021
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17. Philips Respironics Recall of Positive Airway Pressure and Noninvasive Ventilation Devices: A Brief Statement to Inform Response Efforts and Identify Key Steps Forward

Author: Indira Gurubhagavatula, Robert L. Owens, Kevin C. Wilson, and Reena Mehra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Statement (logic), Critical Care and Intensive Care Medicine, Patient-Centered Care, Positive airway pressure, Medicine, Humans, Practice Patterns, Physicians', Intensive care medicine, Societies, Medical, Informed Consent, Noninvasive Ventilation, Ventilators, Mechanical, Recall, Continuous Positive Airway Pressure, business.industry, Editorials, United States, Hypoventilation, Safety-Based Medical Device Withdrawals, Practice Guidelines as Topic, Key (cryptography), Sleep disordered breathing, Noninvasive ventilation, medicine.symptom, Patient Participation, business
Published: 2021

18. Acetazolamide for OSA and Central Sleep Apnea

Author: Bradley A. Edwards, Christopher N. Schmickl, Kimihiko Murase, Shahrokh Javaheri, Robert L. Owens, Jeremy E. Orr, Johan Verbraecken, Shane A. Landry, Kazuo Chin, and Atul Malhotra
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Central sleep apnea, business.industry, Sleep apnea, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, law.invention, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Apnea–hypopnea index, Randomized controlled trial, law, Internal medicine, Meta-analysis, medicine, Number needed to treat, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Acetazolamide, medicine.drug
Abstract: Background Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights. Research Question How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose? Study Design and Methods We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods. Results We included 28 studies (13 OSA/15 CSA; NSubjects,Acetazolamide = 542; NSubjects,Control = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by −0.7 effect sizes (95% CI, −0.83 to −0.58; I2 = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, −44.7 to −31.3) or 13.8/h (95% CI, −16.3 to −11.4; AHIControl = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I2 = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE). Interpretation Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide’s value for the chronic treatment of patients with sleep apnea. Clinical Trial Registration PROSPERO (CRD42019147504)
Published: 2020
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19. The Arousal Threshold as a Drug Target to Improve Continuous Positive Airway Pressure Adherence: Secondary Analysis of a Randomized Trial

Author: Christopher N. Schmickl, Jeremy E. Orr, Robert L. Owens, Pamela N. DeYoung, Bradley A. Edwards, Christopher J. Lettieri, and Atul Malhotra
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Drug target, MEDLINE, Critical Care and Intensive Care Medicine, Arousal, law.invention, Text mining, Randomized controlled trial, law, Internal medicine, Secondary analysis, Correspondence, Humans, Hypnotics and Sedatives, Medicine, Continuous positive airway pressure, Eszopiclone, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, business.industry, Middle Aged, Treatment Outcome, Patient Compliance, Female, business
Published: 2020
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20. Screening for Obstructive Sleep Apnea in a Diverse Bariatric Surgery Population

Author: Macy Mei Sze Lui, Santiago Horgan, Atul Malhotra, Janna R Raphelson, Christopher N. Schmickl, Eduardo Grunvald, Kimberly Y Kreitinger, and Robert L. Owens
Subjects: Adult, Male, medicine.medical_specialty, Polysomnography, Endocrinology, Diabetes and Metabolism, Population, Bariatric Surgery, Medicine (miscellaneous), 030209 endocrinology & metabolism, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Surveys and Questionnaires, medicine, Humans, Mass Screening, 030212 general & internal medicine, Sleep study, education, Retrospective Studies, Sleep Apnea, Obstructive, education.field_of_study, Nutrition and Dietetics, Receiver operating characteristic, business.industry, Epworth Sleepiness Scale, Perioperative, medicine.disease, Obesity, respiratory tract diseases, Surgery, Obstructive sleep apnea, Cohort, Female, business
Abstract: OBJECTIVE: Obstructive sleep apnea (OSA) is common among bariatric surgery patients and is associated with perioperative risk. Preoperative screening is recommended, but some screening tools lack validation, and their relative performance is unclear in this population. The study objective was to compare the ability of four existing tools (STOP-BANG, NO-OSAS, No-Apnea, and the Epworth Sleepiness Scale [ESS]) to screen for moderate to severe OSA in a diverse bariatric cohort. METHODS: Data from patients presenting for first-time bariatric surgery who underwent a sleep study within 1 year of the initial encounter were retrospectively reviewed. Performance of the four tools for detecting moderate to severe OSA was compared based on the area under the receiver operating characteristic curves (AUC). RESULTS: Of the included 214 patients (83.2% female, median age 39 years), 45.3% had moderate to severe OSA. Based on AUC, STOP-BANG (0.75 [95% CI: 0.68–0.81], N = 185), NO-OSAS (0.76 [95% CI: 0.69–0.82], N = 185), and No-Apnea (0.69 [95% CI: 0.62–0.76], N = 190) had similar performance (P > 0.16). Compared with STOP-BANG and NO-OSAS, ESS (0.61 [95% CI: 0.54–0.68], N = 198) had a significantly lower AUC (P < 0.01). Hispanic/Latino self-identification, sex, or obesity class did not significantly modify test performance. CONCLUSIONS: STOP-BANG and NO-OSAS may be preferable to No-Apnea and ESS when screening bariatric surgery patients for moderate to severe OSA. Efforts to screen bariatric patients for OSA are recommended.
Published: 2020
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21. Effects of Hurricanes on Emergency Department Utilization: An Analysis Across 7 US Storms

Author: Zeynal Karaca, Kevin C. Heslin, Molly Hensche, Jeanne S. Ringel, Marguerite L Barrett, Gary Pickens, and Pamela L Owens
Subjects: education.field_of_study, Emergency management, business.industry, Population, Public Health, Environmental and Occupational Health, 030208 emergency & critical care medicine, Storm, Retrospective cohort study, Emergency department, 03 medical and health sciences, 0302 clinical medicine, Geography, Disease category, 030212 general & internal medicine, business, Natural disaster, education, Healthcare Cost and Utilization Project, Demography
Abstract: Objective:Emergency departments (EDs) are critical sources of care after natural disasters such as hurricanes. Understanding the impact on ED utilization by subpopulation and proximity to the hurricane’s path can inform emergency preparedness planning. This study examines changes in ED utilization for residents of 344 counties after the occurrence of 7 US hurricanes between 2005 and 2016.Methods:This retrospective observational study used ED data from the Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases. ED utilization rates for weeks during and after hurricanes were compared with pre-hurricane rates, stratified by the proximity of the patient county to the hurricane path, age, and disease category.Results:The overall population rate of weekly ED visits changed little post-hurricane, but rates by disease categories and age demonstrated varying results. Utilization rates for respiratory disorders exhibited the largest post-hurricane increase, particularly 2–3 weeks following the hurricane. The change in population rates by disease categories and age tended to be larger for people residing in counties closer to the hurricane path.Conclusions:Changes in ED utilization following hurricanes depend on disease categories, age, and proximity to the hurricane path. Emergency managers could incorporate these factors into their planning processes.
Published: 2020
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22. The AWAKE-HF Study: Sacubitril/Valsartan Impact on Daily Physical Activity and Sleep in Heart Failure

Author: Awake-H. F. Study Investigators, Raj M. Khandwalla, Emmanuel Fombu, Kade Birkeland, J. Thomas Heywood, Daniel Grant, Steven R. Steinhubl, and Robert L. Owens
Subjects: medicine.medical_specialty, Ejection fraction, business.industry, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Confidence interval, Sacubitril, 03 medical and health sciences, 0302 clinical medicine, Valsartan, Heart failure, Internal medicine, medicine, Cardiology, Clinical endpoint, Pharmacology (medical), 030212 general & internal medicine, Enalapril, Cardiology and Cardiovascular Medicine, business, Sacubitril, Valsartan, medicine.drug
Abstract: AWAKE-HF evaluated the effect of the initiation of sacubitril/valsartan versus enalapril on activity and sleep using actigraphy in patients who have heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind study, patients with HFrEF (n = 140) were randomly assigned to sacubitril/valsartan or enalapril for 8 weeks, followed by an 8-week open-label phase with sacubitril/valsartan. Primary endpoint was change from baseline in mean activity counts during the most active 30 min/day at week 8. The key secondary endpoint was change in mean nightly activity counts/minute from baseline to week 8. Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) was an exploratory endpoint. There were no detectable differences between groups in geometric mean ratio of activity counts during the most active 30 min/day at week 8 compared with baseline (0.9456 [sacubitril/valsartan:enalapril]; 95% confidence interval [CI] 0.8863–1.0088; P = 0.0895) or in mean change from baseline in activity during sleep (difference: 2.038 counts/min; 95% CI − 0.062 to 4.138; P = 0.0570). Change from baseline to week 8 in KCCQ-23 was 2.89 for sacubitril/valsartan and 4.19 for enalapril, both nonsignificant. In AWAKE-HF, no detectable differences in activity and sleep were observed when comparing sacubitril/valsartan with enalapril in patients with HFrEF using a wearable biosensor. ClinicalTrials.gov, NCT02970669.
Published: 2020
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23. Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline

Author: Robert L. Owens, Shandra L Knight, Richard D. Branson, Simon Oczkowski, Shilpa Rahangdale, John M. Coleman, M. Bradley Drummond, Madalina Macrea, Amanda J. Piper, Dean R. Hess, Bram Rochwerg, Bartolome R. Celli, Naresh M. Punjabi, Jill A. Ohar, Susie Yim-Yeh, Peter J. Wijkstra, and Jeremy E. Orr
Subjects: Pulmonary and Respiratory Medicine, American Thoracic Society Documents, medicine.medical_specialty, COPD, business.industry, Epworth Sleepiness Scale, medicine.medical_treatment, Polysomnogram, noninvasive ventilation, Guideline, Critical Care and Intensive Care Medicine, medicine.disease, hypercapnic respiratory failure, chronic obstructive pulmonary disease, Obstructive sleep apnea, Respiratory failure, Oxygen therapy, Medicine, Noninvasive ventilation, business, Intensive care medicine
Abstract: Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited. Target Audience: Patients with COPD, clinicians who care for them, and policy makers. Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework. Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2–4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty). Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.
Published: 2020

24. Effect of Venlafaxine on Apnea-Hypopnea Index in Patients With Sleep Apnea

Author: Yanru Li, Christopher N. Schmickl, Jeremy E. Orr, Bradley A. Edwards, Scott A. Sands, Atul Malhotra, Robert L. Owens, Rachel Jen, and Pamela N. DeYoung
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Sleep apnea, Venlafaxine, Critical Care and Intensive Care Medicine, Placebo, medicine.disease, Non-rapid eye movement sleep, Crossover study, 03 medical and health sciences, 0302 clinical medicine, Before Bedtime, 030228 respiratory system, Apnea–hypopnea index, Internal medicine, Cardiology, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Reuptake inhibitor, medicine.drug
Abstract: Background One of the key mechanisms underlying OSA is reduced pharyngeal muscle tone during sleep. Data suggest that pharmacologic augmentation of central serotonergic/adrenergic tone increases pharyngeal muscle tone. Research Question We hypothesized that venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would improve OSA severity. Study Design and Methods In this mechanistic, randomized, double-blind, placebo-controlled crossover trial, 20 patients with OSA underwent two overnight polysomnograms ≥ 4 days apart, receiving either 50 mg of immediate-release venlafaxine or placebo before bedtime. Primary outcomes were the apnea-hypopnea index (AHI) and peripheral oxygen saturation (Sp o 2) nadir, and secondary outcomes included sleep parameters and pathophysiologic traits with a view toward understanding the impact of venlafaxine on mechanisms underlying OSA. Results Overall, there was no significant difference between venlafaxine and placebo regarding AHI (mean reduction, –5.6 events/h [95% CI, –12.0 to 0.9]; P = .09) or Sp o 2 nadir (median increase, +1.0% [–0.5 to 5]; P = .11). Venlafaxine reduced total sleep time, sleep efficiency, and rapid eye movement (REM) sleep, while increasing non-REM stage 1 sleep (Pall 0.5, P ≤ .02). Interpretation In unselected patients, venlafaxine simultaneously worsened and improved various pathophysiologic traits, resulting in a zero net effect. Careful patient selection based on pathophysiologic traits, or combination therapy with drugs countering its alerting effects, may produce a more robust response. Trial Registry ClinicalTrials.gov; No.: NCT02714400 ; URL: www.clinicaltrials.gov .
Published: 2020
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25. A Focus Group Evaluation of Breathe Easier: A Mindfulness-Based mHealth App for Survivors of Lung Cancer and Their Family Members

Author: George Mois, Jenay M. Beer, Taylor Kennedy, Karen Kane McDonnell, David G. Gallerani, Otis L. Owens, Kasey N. Smith, and Dane Acena
Subjects: Male, Gerontology, Lung Neoplasms, Health (social science), Mindfulness, South Carolina, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Intervention (counseling), medicine, Humans, Family, Survivors, 030212 general & internal medicine, Lung cancer, mHealth, Qualitative Research, business.industry, Public Health, Environmental and Occupational Health, Focus Groups, medicine.disease, Mobile Applications, Focus group, Telemedicine, 030220 oncology & carcinogenesis, Female, business
Abstract: Purpose:To explore attitudes and acceptance (i.e., intent for future adoption) of survivors of lung cancer and their family members toward a dyad-focused mHealth mindfulness-based intervention (MBI).Approach:Focus groups.Setting:Community hospital setting in South Carolina.Participants:Survivors n = 11 (M = 64.6 years; 73% female; 64% African American) of non-small cell lung cancer (stage I-IIIa) and their family members, n = 8 (M = 58.6 years; 38% female; 75% African American).Intervention:A fully functional prototype mHealth app to deliver a tailored MBI for survivors of lung cancer and their family members.Method:Semi-structured focus groups were conducted and assessed using thematic data analysis to identify the benefits, concerns, needs, and expectations of the app.Results:Convenience and health were the top benefits of using the app, while cost and difficulty of use were the top concerns. Survivors mentioned benefits more than their family members did. Participants felt positively about adding a community network to the app. Finally, participants expected to hear about Breathe Easier from their care provider.Conclusion:Participants perceived a benefit to having credible health information delivered through an mHealth app. Guidance and credible health information regarding lung cancer survivorship should be accessible and convenient for everyone impacted by the disease. Thus, future research should explore platforms for a virtual support system and understanding dissemination of mHealth apps through health care providers.
Published: 2020
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26. After Ringing the Bell: Receptivity of and Preferences for Healthy Behaviors in African American Dyads Surviving Lung Cancer

Author: Daniela B. Friedman, Coretta Jenerette, Otis L. Owens, Karen Kane McDonnell, Brandi R. Newsome, Lisa A. Webb, DeAnne K. Hilfinger Messias, and Callie Campbell King
Subjects: Adult, Male, Lung Neoplasms, Young Adult, 03 medical and health sciences, Underserved Population, Cancer Survivors, Carcinoma, Non-Small-Cell Lung, Surveys and Questionnaires, medicine, Humans, Family, Healthy Lifestyle, Aged, Aged, 80 and over, 030504 nursing, Descriptive statistics, business.industry, Behavior change, Cancer, Patient Preference, Middle Aged, medicine.disease, Focus group, Southeastern United States, Black or African American, Communication Intervention, Quality of Life, Female, Thematic analysis, 0305 other medical science, business, Social cognitive theory, Clinical psychology
Abstract: Purpose To explore receptivity of and preferences for risk-reducing health behavior changes among African American survivors of early-stage lung cancer and their family members. Participants & setting 26 African American non-small cell lung cancer survivor-family member dyads were recruited from two cancer programs in the southeastern United States. Methodologic approach Social cognitive theory principles guided the design and implementation of focus groups. Descriptive statistics were used to summarize the data, and thematic analysis was used to interpret the transcripts from the focus groups. Findings The following four themes were identified. Implications for nursing Participants emphasized the need for improved provider communication. Pragmatic communication interventions for providers, survivors, and family members may facilitate behavior change and improve outcomes among underserved populations.
Published: 2020
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27. Assessing determinants of pre-exposure prophylaxis (PrEP) adherence among a sample of rural Midwestern men who have sex with men (MSM)

Author: Michael Reece, Eva Voorheis, Brian Dodge, Randolph D. Hubach, Jessica Nina Lester, Deana Williams, and Christopher L. Owens
Subjects: Adult, Male, medicine.medical_specialty, Health (social science), Social Psychology, Anti-HIV Agents, Sexual Behavior, Psychological intervention, HIV Infections, Grounded theory, Medication Adherence, Men who have sex with men, Interviews as Topic, Competence (law), Sexual and Gender Minorities, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, Qualitative Research, Motivation, 030505 public health, business.industry, Public Health, Environmental and Occupational Health, Middle Aged, Self Efficacy, United States, Family medicine, Pill, Grounded Theory, Pre-Exposure Prophylaxis, Rural area, 0305 other medical science, business, Qualitative research
Abstract: Pre-exposure prophylaxis (PrEP) efficacy in preventing HIV among gay, bisexual, and other men who have sex with men (MSM) is dependent upon adherence. Little is known about the PrEP adherence experiences among MSM who live in rural areas of the US. This qualitative study was informed by a modified version of Straussian Grounded Theory. Thirty-four 34 rural Midwestern MSM participated in telephone interviews that assessed their PrEP adherence factors. Overall, participants adhered to the PrEP regimen, ranging from missing none to a couple of doses per month. Participants had high self-efficacy (competence) and self-reliance (autonomy) in taking PrEP daily. Participants incorporated PrEP into their already existing routines. Participants were motivated to adhere to prevent HIV acquisition and be financially responsible. All participants mentioned their PrEP provider discussed the importance of adherence with PrEP's effectiveness, but future patient-provider PrEP adherence communication varied among participants. Future PrEP adherence interventions should address counseling strategies that leverage these constructs to support pill taking. Future research should explore patient-provider conversations surrounding PrEP adherence to inform provider- and patient-level interventions.
Published: 2020
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28. Accuracy of WatchPAT for the Diagnosis of Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease

Author: Jeremy E. Orr, Yanru Li, Atul Malhotra, Pamela N. DeYoung, Erik Smales, Robert L. Owens, and Rachel Jen
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Manometry, Polysomnography, Population, Monitoring, Ambulatory, Non-rapid eye movement sleep, Article, Pulmonary function testing, Pulmonary Disease, Chronic Obstructive, Wearable Electronic Devices, Heart Rate, Forced Expiratory Volume, Surveys and Questionnaires, Internal medicine, medicine, Humans, Oximetry, Lead (electronics), education, Aged, Sleep Apnea, Obstructive, COPD, education.field_of_study, medicine.diagnostic_test, business.industry, Snoring, Overlap syndrome, Middle Aged, medicine.disease, Actigraphy, nervous system diseases, respiratory tract diseases, Obstructive sleep apnea, Cardiology, Female, business, psychological phenomena and processes
Abstract: The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), termed the overlap syndrome (OVS), is associated with adverse outcomes that may be reversed with treatment. However, diagnosis is limited by the apparent need for in-laboratory polysomnography (PSG). WatchPAT is a portable diagnostic device that is validated for the diagnosis of OSA that might represent an attractive tool for the diagnosis of OVS. Subjects with established COPD were recruited from a general population. Subjects underwent PSG and simultaneous recording with WatchPAT. Pulmonary function testing and questionnaires were also performed. A total of 36 subjects were recruited and valid data was obtained on 33 (age 63 ± 7, BMI 28 ± 7, 61% male, FEV(1) 56 ± 20% predicted). There was no significant difference in the apnea–hypopnea index (AHI) between PSG and WatchPAT (19 ± 20 versus 20 ± 15 events/h; mean difference 2(−2, 5) events/h; p = 0.381). The AHI was not significantly different in rapid eye movement (REM) and non-rapid eye movement (NREM) determined by PSG versus REM and NREM determined by WatchPAT. WatchPAT slightly overestimated total and REM sleep time, and sleep efficiency. The sensitivity of WatchPAT at an AHI cut-off of ≥5, ≥15, and ≥30 events/h for corresponding PSG AHI cut-offs was 95.8, 92.3, and 88.9, respectively; specificity was 55, 65.0, and 95.8, respectively. WatchPAT is able to determine OSA reliably in patients with COPD. The availability of this additional diagnostic modality may lead to improved detection of OVS, which may in turn lead to improved outcomes for a group of COPD patients at high risk of poor outcomes.
Published: 2020
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29. Self-Rated Health and Structural Racism Indicated by County-Level Racial Inequalities in Socioeconomic Status: The Role of Urban-Rural Classification

Author: Caryn N. Bell and Jessica L. Owens-Young
Subjects: Rural Population, medicine.medical_specialty, Health (social science), Urban Population, Inequality, Health Status, media_common.quotation_subject, Population health, Racism, Health informatics, Article, White People, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Environmental health, medicine, Humans, 030212 general & internal medicine, Socioeconomic status, media_common, Self-rated health, Social Segregation, 030505 public health, Population Health, business.industry, Public health, Public Health, Environmental and Occupational Health, Health Status Disparities, United States, Black or African American, Urban Studies, Social Class, Socioeconomic Factors, Unemployment, Self Report, 0305 other medical science, business, Psychology
Abstract: Recent attention to the interrelationship between racism, socioeconomic status (SES) and health has led to a small, but growing literature of empirical work on the role of structural racism in population health. Area-level racial inequities in SES are an indicator of structural racism, and the associations between structural racism indicators and self-rated health are unknown. Further, because urban-rural differences have been observed in population health and are associated with different manifestations of structural racism, explicating the role of urban-rural classification is warranted. This study examined the associations between racial inequities in SES and self-rated health by county urban-rural classification. Using data from County Health Rankings and American Communities Surveys, black-white ratios of SES were regressed on rates of fair/poor health in U.S. counties. Racial inequities in homeownership were negatively associated with fair/poor health (β = -0.87, s.e. = 0.18), but racial inequities in unemployment were positively associated with fair/poor health (β = 0.03, s.e. = 0.01). The associations between structural racism and fair/poor health varied by county urban-rural classification. Potential mechanisms include the concentration of resources in racially segregated counties with high racial inequities that lead to better health outcomes, but are associated with extreme black SES disadvantage. Racial inequities in SES are a social justice imperative with implications for population health that can be targeted by urban-rural classification and other social contextual characteristics.
Published: 2020
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30. Cytologic processing of ureteral microbiopsies is associated with higher sensitivity for detection of urothelial carcinoma compared with conventional biopsy processing

Author: Vighnesh Walavalkar, Andrew H. Fischer, Jennifer Yates, Todd B. Sheridan, and Christopher L. Owens
Subjects: Adult, Male, Urologic Neoplasms, medicine.medical_specialty, Databases, Factual, Biopsy, Urology, 030209 endocrinology & metabolism, Malignancy, Sensitivity and Specificity, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Ureter, Cytology, medicine, Humans, Kidney Pelvis, Aged, Retrospective Studies, Urothelial carcinoma, Aged, 80 and over, High rate, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Surgical biopsy, Female, Urothelium, business, Renal pelvis, Follow-Up Studies
Abstract: Because of the high rates of false-negative or nondiagnostic ureteral Piranha microbiopsies associated with low cellularity, we assessed the effect of processing these using cytology.We included 2 groups of 44 consecutive microbiopsies processed from formalin as a standard surgical biopsy and 22 processed by cytology. All samples were from the ureter or renal pelvis or calyx. The cytology samples were collected in alcohol-based media and were prepared with a Cellient cell block only (n = 9) or with a Cellient cell block for the visible particles, together with ThinPrep, to capture the remaining desquamated cells (n = 13).Malignancy was diagnosed in 5 of 44 conventionally processed microbiopsies (11%) compared with 14 of 22 cytologically processed microbiopsies (64%; P0.001), including 1 case with invasion. Nineteen site-matched biopsies from 2 patients had undergone both cytologic and surgical processing, with 8 of 8 cytologically processed biopsies diagnosed as malignant. None of the 11 surgically processed biopsies from the same patients matched for site were diagnosed as malignant. Of the 11, 2 (18%) were suspicious for high-grade urothelial carcinoma and 6 (55%) were considered atypical. Increased sensitivity from cytologic processing appears related to increased cell recovery; large numbers of well-preserved urothelial cells were identified in the ThinPrep (range, 1000-25,000 cells/slide), and a nonsignificant trend was found toward increased urothelium (defined as200 cells/profile) in the Cellient cell blocks (14 of 22 [64%]) compared with the histologic biopsies (17 of 44 [39%]; P = 0.070).Cytologic processing of ureteral microbiopsies showed superior sensitivity for detecting high-grade urothelial carcinoma, apparently owing to the increased cellular recovery.
Published: 2020
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31. Envisioning the scientific paper of the future

Author: Laura E. Coristine, Chelsea M. Rochman, Brian L. Owens, Natalie Sopinka, Steven J. Cooke, and Maria C. DeRosa
Subjects: science writing, 0303 health sciences, Open science, Engineering, Multidisciplinary, business.industry, 05 social sciences, science communication, Epistemology, Moment (mathematics), 03 medical and health sciences, Scientific literacy, open science, scholarly publishing, Science communication, lcsh:Q, 0509 other social sciences, lcsh:L, lcsh:Science, 050904 information & library sciences, business, Science writing, lcsh:Education, 030304 developmental biology
Abstract: Consider for a moment the rate of advancement in the scientific understanding of DNA. It is formidable; from Fredrich Miescher’s nuclein extraction in the 1860s to Rosalind Franklin’s double helix X-ray in the 1950s to revolutionary next-generation sequencing in the late 2000s. Now consider the scientific paper, the medium used to describe and publish these advances. How is the scientific paper advancing to meet the needs of those who generate and use scientific information? We review four essential qualities for the scientific paper of the future: ( i) a robust source of trustworthy information that remains peer reviewed and is ( ii) communicated to diverse users in diverse ways, ( iii) open access, and ( iv) has a measurable impact beyond Impact Factor. Since its inception, scientific literature has proliferated. We discuss the continuation and expansion of practices already in place including: freely accessible data and analytical code, living research and reviews, changes to peer review to improve representation of under-represented groups, plain language summaries, preprint servers, evidence-informed decision-making, and altmetrics.
Published: 2020
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32. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010–2017

Author: Jean Y. Ko, Ashley H. Hirai, Pamela L. Owens, Stephen W. Patrick, and Carol Stocks
Subjects: business.industry, West virginia, Obstetrics and Gynecology, Gestational age, Opioid use disorder, General Medicine, medicine.disease, Neonatal abstinence, Opioid, State variation, Hospital discharge, Medicine, business, Healthcare Cost and Utilization Project, medicine.drug, Demography
Abstract: Importance Substantial increases in both neonatal abstinence syndrome (NAS) and maternal opioid use disorder have been observed through 2014. Objective To examine national and state variation in NAS and maternal opioid-related diagnoses (MOD) rates in 2017 and to describe national and state changes since 2010 in the US, which included expanded MOD codes (opioid use disorder plus long-term and unspecified use) implemented inInternational Classification of Disease, 10th Revision, Clinical Modification. Design, Setting, and Participants Repeated cross-sectional analysis of the 2010 to 2017 Healthcare Cost and Utilization Project’s National Inpatient Sample and State Inpatient Databases, an all-payer compendium of hospital discharge records from community nonrehabilitation hospitals in 47 states and the District of Columbia. Exposures State and year. Main Outcomes and Measures NAS rate per 1000 birth hospitalizations and MOD rate per 1000 delivery hospitalizations. Results In 2017, there were 751 037 birth hospitalizations and 748 239 delivery hospitalizations in the national sample; 5375 newborns had NAS and 6065 women had MOD documented in the discharge record. Mean gestational age was 38.4 weeks and mean maternal age was 28.8 years. From 2010 to 2017, the estimated NAS rate significantly increased by 3.3 per 1000 birth hospitalizations (95% CI, 2.5-4.1), from 4.0 (95% CI, 3.3-4.7) to 7.3 (95% CI, 6.8-7.7). The estimated MOD rate significantly increased by 4.6 per 1000 delivery hospitalizations (95% CI, 3.9-5.4), from 3.5 (95% CI, 3.0-4.1) to 8.2 (95% CI, 7.7-8.7). Larger increases for MOD vs NAS rates occurred with newInternational Classification of Disease, 10th Revision, Clinical Modificationcodes in 2016. From a census of 47 state databases in 2017, NAS rates ranged from 1.3 per 1000 birth hospitalizations in Nebraska to 53.5 per 1000 birth hospitalizations in West Virginia, with Maine (31.4), Vermont (29.4), Delaware (24.2), and Kentucky (23.9) also exceeding 20 per 1000 birth hospitalizations, while MOD rates ranged from 1.7 per 1000 delivery hospitalizations in Nebraska to 47.3 per 1000 delivery hospitalizations in Vermont, with West Virginia (40.1), Maine (37.8), Delaware (24.3), and Kentucky (23.4) also exceeding 20 per 1000 delivery hospitalizations. From 2010 to 2017, NAS and MOD rates increased significantly for all states except Nebraska and Vermont, which only had MOD increases. Conclusions and Relevance In the US from 2010 to 2017, estimated rates of NAS and MOD significantly increased nationally and for the majority of states, with notable state-level variation.
Published: 2021
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33. Study Protocol: A Hybrid Delivery of Home-Based Cluster Set Resistance Training for Individuals Previously Treated for Lung Cancer

Author: Morgan T Jones, Carolyn J. Peddle-McIntyre, James Steele, Lauren Marcotte, Christopher Latella, Otis L. Owens, Ciaran M. Fairman, Karen Kane McDonnell, and Kristina L. Kendall
Subjects: business.industry, Computer science, Resistance training, Computational biology, Disease cluster, medicine.disease, Home based, Set (abstract data type), Text mining, medicine, business, Previously treated, Lung cancer, Protocol (object-oriented programming)
Abstract: Background: Symptom burden remains a critical concern for individuals with non-small cell lung cancer (NSCLC) following the completion of treatment. The most common symptom clusters, dyspnea (shortness of breath) and fatigue,can contribute to physical decline, reductions in quality of life, and a higher risk of comorbidities and mortality. Dyspnea is a primary limiter of exercise capacity in individuals with lung cancer, resulting in exercise avoidance and an accelerated physical decline. As such, designing resistance training with cluster sets to mitigate symptoms of dyspnea and fatigue may result in improved exercise tolerance. Thus, maintainingthe exercise stimulus via cluster sets, combined with improved tolerance of the exercise, could result in maintenance of physical function and quality of life. The purpose of this study is to investigate the feasibility and preliminary efficacy of a hybrid-delivery home-based cluster-set resistance training program in individuals with NSCLC. Methods: Individuals with NSCLC (n=15), within 12-months of completion of treatment will be recruited to participate in this single arm feasibility trial. Participants will complete 8-weeks of home-based resistance training designed to minimizedyspnea and fatigue. The hybrid-delivery of the program will include supervised sessions in the participants’ home, and virtual supervision via video conferencing. The primary outcome of feasibility will be quantifiedby recruitment rates, retention, acceptability, and intervention fidelity. Exploratory outcomes (dyspnea, fatigue, quality of life, physical function, and body composition) will be assessed pre- and post- intervention. Discussion: This study will provide important data on the feasibility of delivering this intervention and inform procedures for a future randomized controlled trial. Trial Registration: Record not yet public
Published: 2021
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34. Effects of acetazolamide on control of breathing in sleep apnea patients: Mechanistic insights using meta‐analyses and physiological model simulations

Author: Shane A. Landry, Robert L. Owens, Jeremy E. Orr, Bradley A. Edwards, Christopher N. Schmickl, Brandon Nokes, and Atul Malhotra
Subjects: medicine.medical_specialty, Central sleep apnea, Physiology, Clinical Sciences, Medical Physiology, Models, Biological, Sleep Apnea Syndromes, Models, Physiology (medical), Internal medicine, medicine, QP1-981, Humans, Computer Simulation, Carbonic Anhydrase Inhibitors, Lead (electronics), Lung, business.industry, Respiration, Sleep apnea, Original Articles, Biological, medicine.disease, Acetazolamide, Control of respiration, Breathing, Cardiology, Original Article, Sleep Research, business, Neurocognitive, medicine.drug, Loop gain
Abstract: Obstructive and central sleep apnea affects ~1 billion people globally and may lead to serious cardiovascular and neurocognitive consequences, but treatment options are limited. High loop gain (ventilatory instability) is a major pathophysiological mechanism underlying both types of sleep apnea and can be lowered pharmacologically with acetazolamide, thereby improving sleep apnea severity. However, individual responses vary and are strongly correlated with the loop gain reduction achieved by acetazolamide. To aid with patient selection for long‐term trials and clinical care, our goal was to understand better the factors that determine the change in loop gain following acetazolamide in human subjects with sleep apnea. Thus, we (i) performed several meta‐analyses to clarify how acetazolamide affects ventilatory control and loop gain (including its primary components controller/plant gain), and based on these results, we (ii) performed physiological model simulations to assess how different baseline conditions affect the change in loop gain. Our results suggest that (i) acetazolamide primarily causes a left shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; and (ii) higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline result in a more pronounced loop gain reduction with acetazolamide. In summary, the combination of mechanistic meta‐analyses with model simulations provides a unified framework of acetazolamide’s effects on ventilatory control and revealed physiological predictors of response, which are consistent with empirical observations of acetazolamide's effects in different sleep apnea subgroups. Prospective studies are needed to validate these predictors and assess their value for patient selection., (a) Based on mechanistic meta‐analyses in patients with sleep apnea, acetazolamide primarily causes a left‐shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; the net effect is a relative reduction in overall loop gain similar to the reduction in plant gain. (b) Based on model simulations, a higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline each result in a more pronounced loop gain reduction with acetazolamide, and thus may predict response to acetazolamide.
Published: 2021
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35. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: Insights from the LUNG SAFE study

Author: Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, T Sottiaux, P Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Uhc Mother Theresa, Hektor Sula, Lordian Nunci, Alma Cani, Villa Maria, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Suresh Shindhe, Dk Maizatul Aiman B Pg Hj Ismail, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E Solis-Quesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Miguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tai Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, Pierre-Louis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, Hans-Bernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M 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Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, 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Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo 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M., Rigaud, J. -P., Duranteau, J., Harrois, A., Chabanne, R., Marin, J., Bigot, C., Thibault, S., Ghazi, M., Boukhazna, M., Zein, S. O., Richecoeur, J. R., Combaux, D. M., Grelon, F., Le Moal, C., Sauvadet, E. P., Robine, A., Lemiale, V., Reuter, D., Dres, M., Demoule, A., Goldgran-Toledano, D., Baboi, L., Guerin, C., Lohner, R., Krassler, J., Schafer, S., Zacharowski, K. D., Meybohm, P., Reske, A. W., Simon, P., Hopf, H. -B. F., Schuetz, M., Baltus, T., Papanikolaou, M. N., Papavasilopoulou, T. G., Zacharas, G. A., Ourailogloy, V., Mouloudi, E. K., Massa, E. V., Nagy, E. O., Stamou, E. E., Kiourtzieva, E. V., Oikonomou, M. A., Avila, L. E., Cortez, C. A., Citalan, J. E., Jog, S. A., Sable, S. D., Shah, B., Gurjar, M., Baronia, A. K., Memon, M., Muthuchellappan, R., Ramesh, V. J., Shenoy, A., Unnikrishnan, R., Dixit, S. B., Rhayakar, R. V., Ramakrishnan, N., Bhardwaj, V. K., Mahto, H. L., Sagar, S. V., Palaniswamy, V., Ganesan, D., Jamaati, H., Heidari, F., Meaney, E. 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M., Martinho, A. M., Tomescu, D. R., Marcu, A., Bedreag, O. H., Papurica, M., Corneci, D. E., Negoita, S. I., Grigoriev, E., Gritsan, A. I., Gazenkampf, A. A., Almekhlafi, G., Albarrak, M. M., Mustafa, G. M., Maghrabi, K. A., Salahuddin, N., Aisa, T. M., Al Jabbary, A. S., Tabhan, E., Arabi, Y. M., Trinidad, O. A., Al Dorzi, H. M., Tabhan, E. E., Bolon, S., Smith, O., Mancebo, J., Aguirre-Bermeo, H., Lopez-Delgado, J. C., Esteve, F., Rialp, G., Forteza, C., De Haro, C., Artigas, A., Albaiceta, G. M., De Cima-Iglesias, S., Seoane-Quiroga, L., Ceniceros-Barros, A., Ruiz-Aguilar, A. L., Claraco-Vega, L. M., Soler, J. A., Del Carmen Lorente, M., Hermosa, C., Gordo, F., Miryam-Prieto-Gonzalez, Perez, M. P., Perez, C. P., Allue, R. M., Roche-Campo, F., Ibanez-Santacruz, M., Susana-Temprano, De Pablo, R., Gomez, P. R. A., Ruiz, S. R., Moles, S. I., Jurado, Mª. T., Arizmendi, A., Piacentini, E. A., Franco, N., Honrubia, T., Cheng, M. P., Losada, E. P., Javier-Blanco, Pintado, M. C., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, A., Navarro, G., Cereijo, E., Diaz-Rodriguez, E., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Navalpotro, M. A. B., Abad, R. D., Gonz A Lez, R. M., Toribio, D. A. C. P., Castro, A. G., Artiga, M. J. D., Penuelas, O., Roser, T. P., Olga, M. F., Curto, E. G., Sanchez, R. M., Imma, V. P., Elisabet, G. M., Claverias, L., Magret, M., Pellicer, A. M., Rodriguez, L. L., Sanchez-Ballesteros, J., Gonzalez-Salamanca, A., Jimenez, A. G., Huerta, F. P., Sotillo Diaz, J. C. J., Lopez, E. B., Llinares Moya, D. D., Tallet Alfonso, A. A., Luis, P. S. E., Cesar, P. S., Rafael, S. I., Virgilio, C. G., Recio, N. N., Adamsson, R. O., Rylander, C. C., Holzgraefe, B., Broman, L. M., Wessbergh, J., Persson, L., Schioler, F., Kedelv, H., Tibblin, A. O., Appelberg, H., Hedlund, L., Helleberg, J., Eriksson, K. E., Glietsch, R., Larsson, N., Nygren, I., Nunes, S. L., Morin, A. -K., Kander, T., Adolfsson, A., Zender, H. O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Souissi, A. B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N. K., Ozcelik, M., Unal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Kennedy, B., Parhar, K., Srinivasa, L., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S. K., Ferguson, A., Mckee, R., Raj, A. S., Fawkes, D. A., Watt, P., Twohey, L., Jhamatthew Thomas, R. R., Morton, A., Kadaba, V., Smith, M. J., Hormis, A. P., Kannan, S. G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., O'Neill, O., Seasman, C., Dempsey, G., Scott, C. J., Ellis, H. E., Mckechnie, S., Hutton, P. J., Di Tomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P. D., Williams, A. J., Boyd, O., De Gordoa, L. O. -R., Bramall, J., Symmonds, S., Chau, S. K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., Mccalman, K. H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R. M., Sim, M., Wrathall, D. W., Irvine, D. A., Zantua, K. S., Adams, J. C., Burtenshaw, A. J., Sellors, G. P., Welters, I. D., Williams, K. E., Hessell, R. J., Oldroyd, M. G., Battle, C. E., Pillai, S., Kajtor, I., Sivashanmugavel, M., O'Kane, S. C., Donnelly, A., Frigyik, A. D., Careless, J. P., May, M. M., Stewart, R., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., Macfie, C. C., Dowling, A. T., Nunez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., Franca, A. G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn, J. O., Gomaa, D., Tainter, C., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. M., Tulaimat, A., Choudry, S., Stigler, W., Batra, H., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Judy, C., Saito, S., Kheir, F. M., Kheir, F., Schlichting, A. B., Delsing, A., Crouch, D. R., Elmasri, M., Ismail, D., Dreyer, K. R., Blakeman, T. C., Baron, R. M., Grijalba, C. Q., Hou, P. C., Seethala, R., Aisiku, I., Henderson, G., Frendl, G., Hou, S. -K., Owens, R. L., Schomer, A., Bumbasirevic, V., Jovanovic, B., Surbatovic, M., Veljovic, M., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Graduate School, Intensive Care Medicine, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Madotto, F, Rezoagli, E, Pham, T, Schmidt, M, Mcnicholas, B, Protti, A, Panwar, R, Bellani, G, Fan, E, Van Haren, F, Brochard, L, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Dempaire, G, Theresa, U, Sula, H, Nunci, L, Cani, A, Maria, V, Zazu, A, Dellera, C, Insaurralde, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, A, Mataloun, S, Moock, M, Thompson, M, Goncalves, C, Antonio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, Sales, V, Shindhe, S, Pg Hj Ismail, D, Beloncle, F, Davies, K, Cirone, R, Manoharan, V, Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farias, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreno, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Silesky Jimenez, J, Gonzalez Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Maca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, Llano, M, Burtin, P, Buzancais, G, Beuret, P, Pelletier, N, Mortaza, S, Mercat, A, Chelly, J, Jochmans, S, Terzi, N, Daubin, C, Carteaux, G, De Prost, N, Chiche, J, Daviaud, F, Fartoukh, M, Barberet, G, Biehler, J, Dellamonica, J, Doyen, D, Arnal, J, Briquet, A, Hraiech, S, Papazian, L, Follin, A, Roux, D, Messika, J, Kalaitzis, E, Dangers, L, Combes, A, Au, S, Beduneau, G, Carpentier, D, Zogheib, E, Dupont, H, Ricome, S, Santoli, F, Besset, S, Michel, P, Gelee, B, Danin, P, Goubaux, B, Crova, P, Phan, N, Berkelmans, F, Badie, J, Tapponnier, R, Gally, J, Khebbeb, S, Herbrecht, J, Schneider, F, Declercq, P, Rigaud, J, Duranteau, J, Harrois, A, Chabanne, R, Marin, J, Bigot, C, Thibault, S, Ghazi, M, Boukhazna, M, Zein, S, Richecoeur, J, Combaux, D, Grelon, F, Le Moal, C, Sauvadet, E, Robine, A, Lemiale, V, Reuter, D, Dres, M, Demoule, A, Goldgran-Toledano, D, Baboi, L, Guerin, C, Lohner, R, Krassler, J, Schafer, S, Zacharowski, K, Meybohm, P, Reske, A, Simon, P, Hopf, H, Schuetz, M, Baltus, T, Papanikolaou, M, Papavasilopoulou, T, Zacharas, G, Ourailogloy, V, Mouloudi, E, Massa, E, Nagy, E, Stamou, E, Kiourtzieva, E, Oikonomou, M, Avila, L, Cortez, C, Citalan, J, Jog, S, Sable, S, Shah, B, Gurjar, M, Baronia, A, Memon, M, Muthuchellappan, R, Ramesh, V, Shenoy, A, Unnikrishnan, R, Dixit, S, Rhayakar, R, Ramakrishnan, N, Bhardwaj, V, Mahto, H, Sagar, S, Palaniswamy, V, Ganesan, D, Jamaati, H, Heidari, F, Meaney, E, Nichol, A, Knapman, K, O'Croinin, D, Dunne, E, Breen, D, Jaafar, R, Dwyer, R, Amir, F, Ajetunmobi, O, O'Muircheartaigh, A, Black, C, Treanor, N, Collins, D, Altaf, W, Zani, G, Fusari, M, Spadaro, S, Volta, C, Graziani, R, Brunettini, B, Palmese, S, Formenti, P, Umbrello, M, Lombardo, A, Pecci, E, Botteri, M, Savioli, M, Mattei, A, Schiavoni, L, Tinnirello, A, Todeschini, M, Giarratano, A, Cortegiani, A, Sher, S, Rossi, A, Antonelli, M, Montini, L, Casalena, P, Scafetti, S, Panarello, G, Occhipinti, G, Patroniti, N, Pozzi, M, Biscione, R, Poli, M, Raimondi, F, Albiero, D, Crapelli, G, Beck, E, Pota, V, Schiavone, V, Molin, A, Tarantino, F, Monti, G, Frati, E, Mirabella, L, Cinnella, G, Fossali, T, Colombo, R, Pattarino, P, Mojoli, F, Braschi, A, Borotto, E, Cracchiolo, A, Palma, D, Raponi, F, Foti, G, Vascotto, E, Coppadoro, A, Brazzi, L, Floris, L, Iotti, G, Venti, A, Yamaguchi, O, Takagi, S, Maeyama, H, Watanabe, E, Yamaji, Y, Shimizu, K, Shiozaki, K, Futami, S, Ryosuke, S, Saito, K, Kameyama, Y, Ueno, K, Izawa, M, Okuda, N, Suzuki, H, Harasawa, T, Nasu, M, Takada, T, Ito, F, Shin-Nunomiya, K, Abe, T, Andoh, K, Kusumoto, K, Hirata, A, Takaba, A, Kimura, H, Matsumoto, S, Higashijima, U, Honda, H, Aoki, N, Imai, H, Ogino, Y, Mizuguchi, I, Ichikado, K, Nitta, K, Mochizuki, K, Hashida, T, Tanaka, H, Nakamura, T, Niimi, D, Ueda, T, Kashiwa, Y, Uchiyama, A, Sabelnikovs, O, Oss, P, Haddad, Y, Liew, K, Namendys-Silva, S, Jarquin-Badiola, Y, Sanchez-Hurtado, L, 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D, Marcu, A, Bedreag, O, Papurica, M, Corneci, D, Negoita, S, Grigoriev, E, Gritsan, A, Gazenkampf, A, Almekhlafi, G, Albarrak, M, Mustafa, G, Maghrabi, K, Salahuddin, N, Aisa, T, Al Jabbary, A, Tabhan, E, Trinidad, O, Al Dorzi, H, Bolon, S, Smith, O, Mancebo, J, Aguirre-Bermeo, H, Lopez-Delgado, J, Esteve, F, Rialp, G, Forteza, C, De Haro, C, Artigas, A, Albaiceta, G, De Cima-Iglesias, S, Seoane-Quiroga, L, Ceniceros-Barros, A, Ruiz-Aguilar, A, Claraco-Vega, L, Soler, J, Del Carmen Lorente, M, Hermosa, C, Gordo, F, Lopez-Messa, J, Perez, M, Perez, C, Allue, R, Roche-Campo, F, Ibanez-Santacruz, M, Pintado, M, De Pablo, R, Ruiz, S, Moles, S, Jurado, M, Arizmendi, A, Piacentini, E, Franco, N, Honrubia, T, Cheng, M, Losada, E, Yuste, L, Carbayo-Gorriz, C, Cazorla-Barranquero, F, Alonso, J, Alda, R, Algaba, A, Navarro, G, Cereijo, E, Diaz-Rodriguez, E, Marcos, D, Montero, L, Para, L, Sanchez, R, Navalpotro, M, Abad, R, Gonz A Lez, R, Toribio, D, Castro, A, Artiga, M, Penuelas, O, Roser, T, 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S, Lee, J, Mesar, T, Shinn, J, Gomaa, D, Tainter, C, Yeatts, D, Warren, J, Lanspa, M, Miller, R, Grissom, C, Brown, S, Bauer, P, Gosselin, R, Kitch, B, Cohen, J, Beegle, S, Gueret, R, Tulaimat, A, Choudry, S, Stigler, W, Batra, H, Huff, N, Lamb, K, Oetting, T, Mohr, N, Judy, C, Saito, S, Kheir, F, Schlichting, A, Delsing, A, Crouch, D, Elmasri, M, Ismail, D, Dreyer, K, Blakeman, T, Baron, R, Grijalba, C, Hou, P, Seethala, R, Aisiku, I, Henderson, G, Frendl, G, Hou, S, Owens, R, Schomer, A, Bumbasirevic, V, Jovanovic, B, Surbatovic, M, Veljovic, M, Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, T Sottiaux, P Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Uhc Mother Theresa, Hektor Sula, Lordian Nunci, Alma Cani, Villa Maria, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Suresh Shindhe, Dk Maizatul Aiman B Pg Hj Ismail, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E Solis-Quesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Miguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tai Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, Pierre-Louis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, Hans-Bernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya, Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L Ruiz-Aguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, and LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic
Subjects: ARDS, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Hyperoxemia, Hypoxemia, law.invention, 0302 clinical medicine, law, Fraction of inspired oxygen, Oxygen therapy, Prevalence, Medicine, Hypoxia, Acute respiratory distress syndrome, Hyperoxia, Invasive mechanical ventilation, Mortality, Respiratory Distress Syndrome, Hyperbaric Oxygenation, Respiration, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Intensive Care Units, Anesthesia, Artificial, medicine.symptom, Human, Artificial ventilation, Intensive Care Unit, NO, 03 medical and health sciences, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Humans, business.industry, Research, Respiratory Distress Syndrome, Adult, lcsh:RC86-88.9, medicine.disease, Respiration, Artificial, respiratory tract diseases, Oxygen, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030228 respiratory system, business
Abstract: Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55–100 mmHg) patients (P = 0.47). Conclusions Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073
Published: 2020

36. Statistical uncertainty quantification to augment clinical decision support: a first implementation in sleep medicine

Author: Pamela N. DeYoung, Dae Y. Kang, Robert L. Owens, Todd P. Coleman, and Justin Tantiongloc
Subjects: medicine.medical_specialty, Computer science, Computer applications to medicine. Medical informatics, R858-859.7, Medicine (miscellaneous), Bioengineering, Health Informatics, Medical classification, Machine learning, computer.software_genre, Clinical decision support system, Sleep medicine, Article, Health Information Management, medicine, Human-in-the-loop, Fraction (mathematics), Uncertainty quantification, business.industry, Diagnostic markers, Sleep disorders, Gold standard (test), Translational research, Computer Science Applications, Pattern recognition (psychology), Artificial intelligence, Sleep Research, business, computer
Abstract: Machine learning has the potential to change the practice of medicine, particularly in areas that require pattern recognition (e.g. radiology). Although automated classification is unlikely to be perfect, few modern machine learning tools have the ability to assess their own classification confidence to recognize uncertainty that might need human review. Using automated single-channel sleep staging as a first implementation, we demonstrated that uncertainty information (as quantified using Shannon entropy) can be utilized in a “human in the loop” methodology to promote targeted review of uncertain sleep stage classifications on an epoch-by-epoch basis. Across 20 sleep studies, this feedback methodology proved capable of improving scoring agreement with the gold standard over automated scoring alone (average improvement in Cohen’s Kappa of 0.28), in a fraction of the scoring time compared to full manual review (60% reduction). In summary, our uncertainty-based clinician-in-the-loop framework promotes the improvement of medical classification accuracy/confidence in a cost-effective and economically resourceful manner.
Published: 2021
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37. Determinants of workplace perceptions among federal, state, and local public health staff in the US, 2014 to 2017

Author: Kyle Bogaert, Jonathon P. Leider, Katie Sellers, Jessica L. Owens-Young, Moriah Gendelman, Grace Guerrero-Ramirez, and Brian C. Castrucci
Subjects: Male, medicine.medical_specialty, Job Satisfaction, Surveys and Questionnaires, medicine, Humans, Workplace, Human services, Government, business.industry, Public health, Public Health, Environmental and Occupational Health, United States, Family medicine, Workplace perceptions, Workforce, Intent to leave, Female, Perception, Job satisfaction, Public Health, Public aspects of medicine, RA1-1270, Public health workforce interests and needs survey, Biostatistics, business, Public health workforce, Research Article, Diversity (business), Health department
Abstract: Background The governmental public health workforce in the United States comprises almost 300,000 staff at federal, state, and local levels. The workforce is poised for generational change, experiencing significant levels of retirement. However, intent to leave for other reasons is also substantial, and diversity is lacking in the workforce. Methods Workforce perception data from 76,000 staff from Health and Human Services (HHS) including 14,000 from the Centers for Disease Control and Prevention were analyzed across 2014 and 2017. Additionally, data from 32,000 state and local health department staff in 46 agencies reporting in both years. Estimates were constructed accounting for survey design and non-response. Results In 2017, women made up 43% of the total US government workforce and 33% of supervisors or higher, compared to 73 and 68% generally in State Health Agencies (p p p p Conclusions While intent to leave fell at federal agencies from 2014 to 2017, it increased among staff in state and local health departments. Additionally, while public health is more diverse than the US government overall, significant underrepresentation is observed in supervisory positions for staff of color, especially women.
Published: 2021
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38. Development and testing of 'Is Lung Cancer Screening for You?' A computer-based decision aid

Author: Brandi R. Newsome, Karen Kane McDonnell, Otis L. Owens, and Mark E Humphrey
Subjects: medicine.medical_specialty, Cancer Research, Oncology, business.industry, Computer based, medicine, Medical physics, business, Lung cancer screening
Abstract: Purpose To reduce lung cancer mortality, individuals at high risk should receive a low-dose computed tomography screening annually. To increase the likelihood of screening, interventions that promote shared decision-making are needed. The goal of this study was to investigate the feasibility, acceptability, usability, and preliminary effectiveness of a computer-based decision aid. Methods Thirty-three participants were recruited through primary-care clinics in a small southeastern-US city. Participants used a computer-based decision aid (“Is Lung Cancer Screening for You?”) during a clinic appointment. Paper surveys collected self-reported feasibility, acceptability, and usability data. A research coordinator was present to observe each patient’s and health-care provider’s interactions, and to assess the fidelity of shared decision-making. Results The decision aid was feasible, acceptable for use in a clinic setting, and easy for participants to use. Patients had low decisional conflict following use of the decision aid and had high screening intention and actual screening rates. Shared decision-making discussions using the decision aid were nearly 6 minutes on average. Conclusion Computer-based decision aids are feasible for promoting shared lung cancer–screening decisions. A more robust study is warranted to measure the added value of a computer-based version of this aid versus a paper-based aid.
Published: 2021

39. Change in Perceived Stress and Health Behaviors of Emerging Adults in the Midst of the COVID-19 Pandemic

Author: Rhea L. Owens, Elaine Marshall, Rick A. LaCaille, Stephanie A. Hooker, and Lara J. LaCaille
Subjects: Male, Coronavirus disease 2019 (COVID-19), Adolescent, Universities, Health Behavior, Physical activity, Anxiety, Young Adult, Surveys and Questionnaires, Pandemic, Stress (linguistics), Adaptation, Psychological, Medicine, Humans, Longitudinal Studies, Students, Exercise, Pandemics, General Psychology, Depression (differential diagnoses), business.industry, SARS-CoV-2, COVID-19, Mental health, United States, Psychiatry and Mental health, Distress, Mental Health, Female, medicine.symptom, Sedentary Behavior, business, Stress, Psychological, Clinical psychology
Abstract: Background The COVID-19 pandemic has resulted in unprecedented disruptions, restrictions, and concerns about physical and mental health. Emerging adulthood, including the first year of college, is associated with declines in healthy eating and physical activity, as well as possible heightened distress. The impact of COVID-19 may exacerbate these concerns. Purpose The purpose of this study was to examine changes in health behaviors and perceived stress in emerging adults over the first year of college and to determine whether prepandemic health behaviors were protective for mental health and stress during the initial changes after the COVID-19 pandemic. Methods First-year college students (N = 234, 58.6% female) completed three surveys during their first year of school, the third being after the onset of COVID-19 and during a stay-at-home order. At Time 3, we also assessed symptoms of anxiety and depression. Results Using linear mixed modeling, sedentary time increased and physical activity decreased over time, but 20%–35% of students reported improvements in these behaviors. Dietary changes appeared mixed, with some improvements noted early during COVID-19. Perceived stress increased over time. Multiple regression indicated that of the health behaviors examined for protective effects on mental health and stress during the pandemic, only diet quality emerged as a significant predictor. Conclusions Although notable declines in some health habits were observed over time, including following COVID-19 disruptions, some students reported improved health behaviors. Efforts should be directed at identifying and intervening with students most at risk for poor functioning.
Published: 2021

40. A Pilot Randomized Controlled Trial of Effect of Genioglossus Muscle Strengthening on Obstructive Sleep Apnea Outcomes

Author: Todd Morgan, Naa-Oye Bosompra, Atul Malhotra, Bradley A. Edwards, Stacie Moore, Robert L. Owens, Pamela N. DeYoung, Janelle Fine, Rachel Jen, Dillon Gilbertson, Maryam Maghsoudipour, Brandon Nokes, and Yanru Li
Subjects: Mandibular advancement splint, medicine.medical_treatment, Clinical Trials and Supportive Activities, Clinical Sciences, Article, Pittsburgh Sleep Quality Index, stomatognathic system, Clinical Research, Positive airway pressure, medicine, Continuous positive airway pressure, Lung, obstructive sleep apnea, Genioglossus, business.industry, Epworth Sleepiness Scale, adjunctive treatment, Sleep apnea, General Medicine, respiratory system, medicine.disease, mandibular advancement splint, nervous system diseases, respiratory tract diseases, Obstructive sleep apnea, Anesthesia, Medicine, genioglossus muscle, Sleep Research, business, continuous positive airway pressure
Abstract: The genioglossus is a major upper airway dilator muscle. Our goal was to assess the efficacy of upper airway muscle training on Obstructive Sleep Apnea (OSA) as an adjunct treatment. Sixty-eight participants with OSA (AHI &gt, 10/h) were recruited from our clinic. They fall into the following categories: (a) Treated with Automatic Positive Airway Pressure (APAP), (n = 21), (b) Previously failed APAP therapy (Untreated), (n = 25), (c) Treated with Mandibular Advancement Splint (MAS), (n = 22). All subjects were given a custom-made tongue strengthening device. We conducted a prospective, randomized, controlled study examining the effect of upper airway muscle training. In each subgroup, subjects were randomized to muscle training (volitional protrusion against resistance) or sham group (negligible resistance), with a 1:1 ratio over 3 months of treatment. In the baseline and the final visit, subjects completed home sleep apnea testing, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), SF-36 (36-Item Short Form Survey), and Psychomotor Vigilance Test (PVT). Intervention (muscle training) did not affect the AHI (Apnea-Hypopnea Index), (p-values &gt, 0.05). Based on PSQI, ESS, SF-36 scores, and PVT parameters, the changes between the intervention and sham groups were not significant, and the changes were not associated with the type of treatment (p-value &gt, 0.05). The effectiveness of upper airway muscle training exercise as an adjunct treatment requires further study.
Published: 2021

41. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses: Analysis of ICD-10-CM Transition, 2013-2017

Author: Jean Y. Ko, Ashley H. Hirai, Carol Stocks, Pamela L Owens, and Stephen W. Patrick
Subjects: medicine.medical_specialty, Population, Rate ratio, Pediatrics, Interrupted Time Series Analysis, International Classification of Diseases, Pregnancy, medicine, Humans, Healthcare Cost and Utilization Project, education, education.field_of_study, business.industry, Obstetrics, Infant, Newborn, ICD-10, Infant, Opioid use disorder, General Medicine, medicine.disease, Opioid-Related Disorders, Confidence interval, Analgesics, Opioid, Hospitalization, Opioid, Pediatrics, Perinatology and Child Health, Female, business, Neonatal Abstinence Syndrome, medicine.drug
Abstract: BACKGROUND AND OBJECTIVES Hospital discharge records remain a common data source for tracking the opioid crisis among pregnant women and infants. The International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) transition from the International Classification of Diseases, Ninth Revision, Clinical Modification may have affected surveillance. Our aim was to evaluate this transition on rates of neonatal abstinence syndrome (NAS), maternal opioid use disorder (OUD), and opioid-related diagnoses (OUD with ICD-10-CM codes for long-term use of opioid analgesics and unspecified opioid use). METHODS Data from the 2013–2017 Healthcare Cost and Utilization Project’s National Inpatient Sample were used to conduct, interrupted time series analysis and log-binomial segmented regression to assess whether quarterly rates differed across the transition. RESULTS From 2013 to 2017, an estimated 18.8 million birth and delivery hospitalizations were represented. The ICD-10-CM transition was not associated with NAS rates (rate ratio [RR]: 0.99; 95% confidence interval [CI]: 0.90–1.08; P = .79) but was associated with 11% lower OUD rates (RR: 0.89; 95% CI: 0.80–0.98; P = .02) and a decrease in the quarterly trend (RR: 0.98; 95% CI: 0.96–1.00; P = .04). The transition was not associated with maternal OUD plus long-term use rates (RR: 0.98; 95% CI: 0.89–1.09; P = .76) but was associated with a 20% overall increase in opioid-related diagnosis rates including long-term and unspecified use (RR: 1.20; 95% CI: 1.09–1.32; P < .001). CONCLUSIONS The ICD-10-CM transition did not appear to affect NAS. However, coding of maternal OUD alone may not capture the same population across the transition, which confounds the interpretation of trend data spanning this time period.
Published: 2021

42. Practices and Patterns of Hourly Neurochecks: Analysis of 8,936 Patients With Neurological Injury

Author: Biren B. Kamdar, Jamie Nicole LaBuzetta, Robert L. Owens, Brian R. Hirshman, and Atul Malhotra
Subjects: medicine.medical_specialty, Neurological injury, medicine.diagnostic_test, Critical Care, business.industry, Neurological examination, Critical Care and Intensive Care Medicine, Intensive care unit, Quality Improvement, Article, law.invention, Hospitalization, 03 medical and health sciences, Intensive Care Units, 0302 clinical medicine, law, Emergency medicine, medicine, Humans, 030212 general & internal medicine, business, 030217 neurology & neurosurgery, Retrospective Studies
Abstract: Background: Patients experiencing acute neurological injury often receive hourly neurological assessments (“neurochecks”) to capture signs of deterioration. While commonly utilized in the intensive care unit (ICU) setting, little is known regarding practices (i.e., variations by age and ordering services) and patterns (i.e., duration and post-discontinuation plans) of hourly neurochecks. To inform future quality improvement intervention efforts, we performed an analysis of hourly neurochecks using an electronic health record-based dataset. Study Design and Methods: Our 75-month retrospective dataset consisted of all health system ICU patients who received hourly neurochecks. Variables included age, admission diagnosis category, ordering provider, post-discontinuation order, and discharge destination. Multivariable Cox regression was used to evaluate factors associated with hourly neurocheck duration. Results: We evaluated 9,513 first admission hourly neurocheck orders in 8,936 patients. The trauma, neurosurgery, and neurocritical care services were responsible for 4,067 (43%), 2,071 (22%) and 1,697 (18%) hourly neurocheck orders, respectively. Median (interquartile range) hourly neurocheck duration was 1.09 (0.69, 2.35) days, and was greater than 3 and 7 days, respectively, for 1,773 (19%) and 640 (7%) patients. Median hourly neurocheck duration ranged from 0.87 (0.65, 1.68) to 1.60 (0.83, 2.97) days for neurosurgical and non-neurological ICU services, respectively. Upon discontinuation, 2,225 (23%) of hourly neurochecks were transitioned to no neurochecks. Conclusion: Substantial differences exist between ICU services and practice patterns surrounding hourly neurochecks. Understanding these differences will help inform intervention efforts aimed at streamlining hourly neurocheck practices and outcomes for patients with acute neurological injury.
Published: 2021

43. Why do we sometimes ignore the chief complaint in patients evaluated for obstructive sleep apnea?

Author: Brandon Nokes, Atul Malhotra, Robert L. Owens, and Pamela N. DeYoung
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Sleep Apnea, Clinical Sciences, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Complaint, Psychology, Humans, Medicine, In patient, Letters to the Editor, Sleep Apnea, Obstructive, Neurology & Neurosurgery, Other Medical and Health Sciences, Obstructive, business.industry, Extramural, Snoring, medicine.disease, Sleep in non-human animals, Obstructive sleep apnea, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Citation:Malhotra A, Nokes B, DeYoung P, Owens R. Why do we sometimes ignore the chief complaint in patients evaluated for obstructive sleep apnea? J Clin Sleep Med. 2020;16(4):657–659.
Published: 2020
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44. Activity Sensors to Evaluate the Effect of Sacubitril/Valsartan on Quality‐of‐Life in Heart Failure: rational and design of the AWAKE‐HF study

Author: Raj M. Khandwalla, Kade Birkeland, Steven R. Steinhubl, Emmanuel Fombu, Jerome B. Riebman, J. Thomas Heywood, Kevin McCague, Daniel Grant, and Robert L. Owens
Subjects: Adult, Male, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Adolescent, Study Designs, Tetrazoles, Context (language use), Heart failure, 030204 cardiovascular system & hematology, Sacubitril, Angiotensin Receptor Antagonists, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Accelerometry, Humans, Medicine, 030212 general & internal medicine, Sacubitril/valsartan, Aged, Monitoring, Physiologic, Aged, 80 and over, Study Design, business.industry, Physical activity, Aminobutyrates, Biphenyl Compounds, Actigraphy, Middle Aged, Drug Combinations, Valsartan, Health‐related quality of life, lcsh:RC666-701, Ambulatory, Quality of Life, Physical therapy, Female, Observational study, Cardiology and Cardiovascular Medicine, business, Sleep, Sacubitril, Valsartan, Biosensor, medicine.drug
Abstract: Aims Limited data are available regarding the ability of sacubitril/valsartan to provide clinically meaningful health‐related quality of life (HRQoL) improvements among individuals with heart failure (HF). Objective measurement of physical activity and sleep using actigraphy can provide insight into daily functioning and HRQoL. Methods and results We designed an 18 week, multicenter, randomized, double‐blind, double‐dummy, parallel‐group study to objectively assess changes in function and HRQoL directly after initiating sacubitril/valsartan vs. enalapril in participants with HF in their home environments. A total of 136 outpatient, ambulatory participants with New York Heart Association Class II or III HF with reduced ejection fraction (HFrEF) will be included in the study. Patients will undergo a 2 week baseline observational phase (continuing current HF treatment); data from the second week of this phase will be the baseline value for comparison with those of subsequent periods. Patients will then enter an 8 week blinded‐treatment phase (randomly assigned 1:1 to sacubitril/valsartan or enalapril), followed by an 8 week open‐label extension phase (treatment with only sacubitril/valsartan). The primary efficacy endpoint is the change in mean activity counts during the most active 30 min of the participant's day between baseline and the final randomized treatment phase measurement. Secondary endpoints include the change in mean sleep activity during the randomized and open‐label phases; questionnaires will also assess HRQoL measures. Rather than analysing pooled actigraphy data, the researchers are considering each participant to be acting as his or her own control. Conclusions This will be the first study to assess the effects of sacubitril/valsartan on objective measures of sleep and activity in individuals with HFrEF within the context of their daily lives. Wearable accelerometer devices will be used to gain insight into how the medication affects physical activity and sleep.
Published: 2019

45. Ramelteon for Prevention of Postoperative Delirium

Author: Andrew J Heisel, Robert L. Owens, Michael M. Madani, Anuja Vyas, Stuti J. Jaiswal, Victor Pretorius, Atul Malhotra, Nick H. Kim, Ashna Aggarwal, Timothy M. Fernandes, Kim M. Kerr, William R. Auger, and Haritha Ackula
Subjects: Adult, Male, medicine.medical_treatment, Ramelteon, MEDLINE, Endarterectomy, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, mental disorders, Humans, Medicine, Aged, Pulmonary thromboendarterectomy, business.industry, Delirium, 030208 emergency & critical care medicine, Perioperative, Middle Aged, Indenes, 030228 respiratory system, Elective Surgical Procedures, Anesthesia, Female, medicine.symptom, business, Elective Surgical Procedure, medicine.drug
Abstract: To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting.Parallel-arm, randomized, double-blinded, placebo-controlled trial.Academic medical center in La Jolla, California.Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy.Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU.Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively.Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.
Published: 2019
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46. More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea

Author: Bradley A. Edwards, Scott A. Sands, Robert L. Owens, and Susan Redline
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Endotype, medicine.medical_specialty, Genotype, medicine.medical_treatment, Concise Translational Review, Clinical manifestation, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Continuous positive airway pressure, Precision Medicine, Intensive care medicine, Aged, Aged, 80 and over, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, business.industry, Clinical study design, Disease classification, Middle Aged, medicine.disease, nervous system diseases, respiratory tract diseases, Obstructive sleep apnea, Phenotype, 030228 respiratory system, Practice Guidelines as Topic, Etiology, Female, Personalized medicine, business
Abstract: Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea–hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.e., endotype) and clinical manifestation (i.e., phenotype) of OSA in an individual are not well described by the AHI. We define and review the important progress made in understanding and measuring physiological mechanisms (or endotypes) that help define subtypes of OSA and identify the potential use of genetics to further refine disease classification. This more detailed understanding of OSA pathogenesis should influence clinical treatment decisions as well as help inform research priorities and clinical study design. In short, treatments could be individualized on the basis of the underlying cause of OSA; patients could better understand which symptoms and outcomes will respond to OSA treatment and by how much; and researchers could select populations most likely to benefit from specific treatment approaches for OSA.
Published: 2019
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47. Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey

Author: Gabriel Wardi, Ian Joel, Julian Villar, Michael Lava, Eric Gross, Vaishal Tolia, Raghu R. Seethala, Robert L. Owens, Rebecca E. Sell, Sydney B. Montesi, Farbod N. Rahaghi, Somnath Bose, Ashish Rai, Elizabeth K. Stevenson, Jakob McSparron, and Jeremy R. Beitler
Subjects: Resuscitation, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Nursing, 030204 cardiovascular system & hematology, Cardiovascular, Critical Care and Intensive Care Medicine, Body weight, Article, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Sepsis, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Heart Failure, Septic, Septic shock, business.industry, Inflammatory and immune system, systolic heart failure, Shock, Stroke Volume, Hematology, medicine.disease, Shock, Septic, Emergency & Critical Care Medicine, fluid challenge, Clinical Practice, crystalloid, Infectious Diseases, Heart Disease, Anesthesia, Heart failure, Shock (circulatory), Therapeutic Equipoise, Fluid Therapy, septic shock, medicine.symptom, Infection, business, Fluid challenge, Volume (compression)
Abstract: Purpose: International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. Methods: We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) Results: A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF ( P < .01). Emergency medicine physicians were most likely to feel that Conclusions: Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.
Published: 2019
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48. Impact of Sleep Deprivation in the Neurological Intensive Care Unit: A Narrative Review

Author: Jamie Nicole LaBuzetta, Robert L. Owens, and Victoria A. Chang
Subjects: medicine.medical_specialty, Neurology, Critical Illness, Adrenergic beta-Antagonists, Review, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Central Nervous System Diseases, law, Intensive care, medicine, Humans, Hypnotics and Sedatives, Vasoconstrictor Agents, Intensive care unit, Brain injury, Psychiatry, Lighting, Sleep disorder, business.industry, Neuropsychology, 030208 emergency & critical care medicine, medicine.disease, Sleep in non-human animals, Analgesics, Opioid, Sleep deprivation, Intensive Care Units, Health Facility Environment, Patient Care, Neurology (clinical), medicine.symptom, Neurological intensive care unit, Sleep, Noise, business, 030217 neurology & neurosurgery
Abstract: Sleep is fundamental for everyday functioning, yet it is often negatively impacted in critically ill patients by the intensive care setting. With a focus on the neurological intensive care unit (NeuroICU), this narrative review summarizes methods of measuring sleep and addresses common causes of sleep disturbance in the hospital including environmental, pharmacological, and patient-related factors. The effects of sleep deprivation on the cardiovascular, pulmonary, immune, endocrine, and neuropsychological systems are discussed, with a focus on short-term deprivation in critically ill populations. Where evidence is lacking in the literature, long-term sleep deprivation studies and the effects of sleep deprivation in healthy individuals are also referenced. Lastly, strategies for the promotion of sleep in the NeuroICU are presented.
Published: 2019
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49. Using Tiered Coaching and Bug-in-Ear Technology to Promote Teacher Implementation Fidelity

Author: Ya-yu Lo, Belva C. Collins, and Tosha L. Owens
Subjects: 050103 clinical psychology, Medical education, Implementation fidelity, Self-management, business.industry, media_common.quotation_subject, 05 social sciences, Rehabilitation, Professional development, 050301 education, Fidelity, General education, Coaching, Education, Intervention (counseling), Assistive technology, ComputingMilieux_COMPUTERSANDEDUCATION, 0501 psychology and cognitive sciences, business, Psychology, 0503 education, media_common
Abstract: In this study, we examined the effects of a tiered teacher coaching intervention package, including video coaching and in situ coaching with use of the bug-in-ear technology, on the implementation fidelity of four general education teachers in supporting students with persistent off-task behaviors to self-monitor own behaviors in the general education setting. In addition, we evaluated the effects of teachers’ implementation on the on-task behavior of four target students. Results of the multiple probe across participants design showed that there was a functional relation between the tiered coaching intervention and the teachers’ implementation fidelity. There was also an overall improvement in all of the four students’ on-task behaviors. Limitations, suggestions for future research, and implications for practice are discussed.
Published: 2019
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50. Are decision aids leading to shared prostate cancer screening decisions among African-American men?: iDecide

Author: Simon P. Kim, Abbas Tavakoli, and Otis L. Owens
Subjects: Male, Cancer Research, medicine.medical_specialty, Health Personnel, Decision Making, Ethnic group, Intention, Affect (psychology), Decision Support Techniques, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Surveys and Questionnaires, Health care, medicine, Decision aids, Humans, 030212 general & internal medicine, Early Detection of Cancer, Aged, business.industry, Public health, Prostatic Neoplasms, Middle Aged, medicine.disease, Black or African American, Prostate cancer screening, Oncology, 030220 oncology & carcinogenesis, Family medicine, business
Abstract: African-Americans have prostate cancer mortality rates that are double their White counterparts. To reduce prostate cancer disparities, it is suggested that men engage in shared decision making about prostate cancer screening with their healthcare provider after learning about the benefits and harms of these screenings. While researchers have developed decision aids to support African-American’s screening decisions, there is some uncertainty whether these aids lead to shared decision making. The goal of the current study was to investigate the efficacy of iDecide, a computerized decision aid, for promoting African-American men’s engagement in shared decision making. Six months after their use of iDecide, a prostate cancer screening decision aid, 76 participants were surveyed to determine whether they spoke with a provider about screening, what this conversation entailed, and if shared decision making occurred. While iDecide is an effective tool for enhancing African-American’s intention to engage in shared decision making, there is no evidence this aid increased their likelihood of discussing prostate cancer with a provider or participation in shared decision making. Future research should employ stronger research designs and assess the various contexts that can affect the relationship between decision-aid use and shared decision making among African-Americans.
Published: 2019
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