Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 A Living Systematic Review of Multiple Streams of Evidence

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187) Data Sources: 21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020. Study Selection: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. Data Extraction: Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). Data Synthesis: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. Limitation: Direct studies in COVID-19 are limited and poorly reported. Conclusion: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers

Associations between continuity of primary and specialty physician care and use of hospital-based care among community-dwelling older adults with complex care needs.

ObjectiveWhile research suggests that higher continuity of primary and specialty physician care can improve patient outcomes, their effects have rarely been examined and compared concurrently. We investigated associations between continuity of primary and specialty physician care and emergency department visits and hospital admissions among community-dwelling older adults with complex care needs.MethodsWe conducted a retrospective cohort study of home care patients in Ontario, Canada, from October 2014 to September 2016. We measured continuity of primary and specialty physician care over the two years prior to a home care assessment and categorized them into low, medium, and high groups using terciles of the distribution. We used Cox regression models to concurrently test the associations between continuity of primary and specialty care and risk of an emergency department visit and hospital admission within six months of assessment, controlling for potential confounders. We examined interactions between continuity of care and count of chronic conditions, count of physician specialties seen, functional impairment, and cognitive impairment.ResultsOf 178,686 participants, 49% had an emergency department visit during follow-up and 27% had a hospital admission. High vs. low continuity of primary care was associated with a reduced risk of an emergency department visit (HR = 0.90 (0.89-0.92)) as was continuity of specialty care (HR = 0.93 (0.91-0.95)). High vs. low continuity of primary care was associated also with a reduced risk of a hospital admission (HR = 0.94 (0.92-0.96)) as was continuity of specialty care (HR = 0.92 (0.90-0.94)). The effect of continuity of specialty care was moderately stronger among patients who saw four or more physician specialties.ConclusionHigher continuity of primary physician and specialty physician care had independent, protective effects of similar magnitude against emergency department use and hospital admissions. Improving continuity of specialty care should be a priority alongside improving continuity of primary care in complex, older adult populations with significant specialist use

Risk of Relapse of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids.

Publication status: PublishedOBJECTIVE: Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. METHODS: We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time-to-event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. RESULTS: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4-12.1) relapses per 100 patient-years. Neither the use of PLEX (subhazard ratio 0.91-0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93-0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3-ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. CONCLUSION: In patients with severe ANCA-associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk

Increased abundance of opioid receptor heteromers after chronic morphine administration.

The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction

Increased abundance of opioid receptor heteromers after chronic morphine administration.

The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN: The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING: The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS: We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS: Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence