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Author(s): Yaseen M. Arabi [sup.1], Janet Diaz [sup.2], François Lamontagne [sup.3] Author Affiliations: (1) grid.412149.b, 0000 0004 0608 0662, Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard-Health [...]

PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.ResultsWe randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Author(s): Paul J. Young [sup.1] [sup.2] [sup.3] [sup.4], François Lamontagne [sup.5], Tomoko Fujii [sup.3] [sup.6] [sup.7] Author Affiliations: (1) grid.416979.4, 0000 0000 8862 6892, Intensive Care Unit, Wellington Hospital, , [...]

Purpose Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets. Methods We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration's instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality. Results Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87-1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33-6.74). Conclusions Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients., Author(s): François Lamontagne [sup.1] [sup.2], Andrew G. Day [sup.3], Maureen O. Meade [sup.4] [sup.5], Deborah J. Cook [sup.4] [sup.5], Gordon H. Guyatt [sup.5], Mathieu Hylands [sup.6], Peter Radermacher [sup.7], Jean-Marie [...]

Author(s): Francois Lamontagne [sup.1] , John C. Marshall [sup.2] , Neill K. J. Adhikari [sup.3] Author Affiliations: (1) 0000 0000 9064 6198, grid.86715.3d, Centre de recherche du CHU de Sherbrooke [...]

Purpose To provide a 360-degree description of ICU-to-ward transfers. Methods Prospective cohort study of 451 adults transferred from a medical-surgical ICU to a hospital ward in 10 Canadian hospitals July 2014-January 2016. Transfer processes documented in the medical record. Patient (or delegate) and provider (ICU/ward physician/nurse) perspectives solicited by survey 24-72 h after transfer. Results Medical records (100%) and survey responses (ICU physicians-80%, ICU nurses-80%, ward physicians-46%, ward nurses-64%, patients-74%) were available for most transfers. The median time from initiation to completion of transfer was 25 h (IQR 6-52). ICU physicians and nurses reported communicating with counterparts via telephone (78 and 75%) when transfer was requested (82 and 24%) or accepted (31 and 59%) and providing more elements of clinical information than ward physicians (mean 4.7 vs. 3.9, p < 0.001) and nurses (5.0 vs. 4.4, p < 0.001) reported receiving. Patients were more likely to report satisfaction with the transfer when they received more information (OR 1.32, 95% CI 1.18-1.48), had their questions addressed (OR 3.96, 95% CI 1.33-11.84), met the ward physician prior to transfer (OR 4.61, 95% CI 2.90-7.33), and were assessed by a nurse within 1 h of ward arrival (OR 4.70, 95% CI 2.29-9.66). Recommendations for improvement included having a documented care plan travel with the patient (all stakeholders), standardized face-to-face handover (physicians), avoiding transfers at shift change (nurses) and informing patients about pending transfers in advance (patients). Conclusions ICU-to-ward transfers are characterized by failures of patient flow and communication; experienced differently by patients, ICU/ward physicians and nurses, with distinct suggestions for improvement., Author(s): Henry T. Stelfox [sup.1], Jeanna Parsons Leigh [sup.2], Peter M. Dodek [sup.3], Alexis F. Turgeon [sup.4], Alan J. Forster [sup.5], Francois Lamontagne [sup.6], Rob A. Fowler [sup.7], Andrea Soo [...]

Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field., Author(s): Anders Perner [sup.1], Anthony C. Gordon [sup.2], Derek C. Angus [sup.3], Francois Lamontagne [sup.4], Flavia Machado [sup.5], James A. Russell [sup.6], Jean-Francois Timsit [sup.7], John C. Marshall [sup.8], John [...]

Purpose In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock. Methods We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60-65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups. Results A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36 %, p = 0.07) and hospital mortality (30 versus 33 %, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %, p = 0.03) but not in younger patients. Conclusions This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy., Author(s): François Lamontagne [sup.1] [sup.2] [sup.3], Maureen O. Meade [sup.4] [sup.5], Paul C. Hébert [sup.6], Pierre Asfar [sup.7], François Lauzier [sup.8] [sup.9] [sup.25], Andrew J.E. Seely [sup.10] [sup.11], Andrew G. [...]

Purpose: To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. Methods: This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m2. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the effect of RRT initiation strategy on outcomes by CKD status. Results: We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114–160) and 76 (64–90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79–1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05–3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41–7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34–1.47, p value for interaction, 0.009). Conclusion: In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD. [ABSTRACT FROM AUTHOR]

Rhode Island Hospital: Matthew Lynch; AnnMarie O'Mara; Syed Naeem; Sairah Sharif; Joyce McKenney Goulart. Worthing Hospital, Western Sussex Hospitals NHS Foundation Trust: Luke E. Hodgson; Indra Chadbourn; Raquel Gomez; Jordi Margalef. Nottingham University Hospital-Queen's Medical Centre: Andrew Sharman; Megan Meredith; Lucy Ryan; Louise Conner; Cecilia Peters; Dan Harvey. The Miriam Hospital: Matthew Lynch; AnnMarie O'Mara; Syed Naeem; Sairah Sharif; Joyce McKenney Goulart. [Extracted from the article]

Plasma anti-SARS-CoV2 IgG, IgA, and IgM antibody isotypes were quantified, and changes in their concentrations from day 4 to 7 were investigated for association with mortality and use of ventilation or vasopressors. In conclusion, in acute COVID-19 hospitalized patients, the concentrations of IgG, IgA, and IgM binding antibodies against SARS-CoV-2 increased significantly from day 4 to day 7. [Extracted from the article]