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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.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Introduction: The goal of emergency airway management is first pass success without adverse events (FPS-AE). Anatomically difficult airways are well appreciated to be an obstacle to this goal. However, little is known about the effect of the physiologically difficult airway with regard to FPS-AE. This study evaluates the effects of both anatomically and physiologically difficult airways on FPS-AE in patients undergoing rapid sequence intubation (RSI) in the emergency department (ED).Methods: We analyzed prospectively recorded intubations in a continuous quality improvement database between July 1, 2014–June 30, 2018. Emergency medicine (EM) or emergency medicine/pediatric (EM-PEDS) residents recorded patient, operator, and procedural characteristics on all consecutive adult RSIs performed using a direct or video laryngoscope. The presence of specific anatomically and physiologically difficult airway characteristics were also documented by the operator. Patients were analyzed in four cohorts: 1) no anatomically or physiologically difficult airway  characteristics; 2) one or more anatomically difficult airway characteristics; 3) one or more physiologically difficult airway characteristics; and 4) both anatomically and physiologically difficult airway characteristics. The primary outcome was FPS-AE. We performed a multivariable logistic regression analysis to determine the association between anatomically difficult airways or physiologically difficult airways and FPS-AE.Results: A total of 1513 intubations met inclusion criteria and were analyzed. FPS-AE for patients without any difficult airway characteristics was 92.4%, but reduced to 82.1% (difference = - 10.3%, 95% confidence interval (CI), - 14.8% to - 5.6%) with the presence of one or more anatomically difficult airway characteristics, and 81.7% (difference = - 10.7%, 95% CI, - 17.3% to - 4.0%) with the presence of one or more physiologically difficult airway characteristics. FPS-AE was further reduced to 70.9% (difference = - 21.4%, 95% CI, - 27.0% to - 16.0%) with the presence of both anatomically and physiologically difficult airway characteristics. The adjusted odds ratio (aOR) of FPS-AE was 0.37 [95% CI, 0.21 - 0.66] in patients with anatomically difficult airway characteristics and 0.36 [95% CI, 0.19 - 0.67] for patients with physiologically difficult airway characteristics, compared to patients with no difficult airway characteristics. Patients who had both anatomically and physiologically difficult airway characteristics had a further decreased aOR of FPS-AE of 0.19 [95% CI, 0.11 - 0.33].Conclusion: FPS-AE is reduced to a similar degree in patients with anatomically and physiologically difficult airways. Operators should assess and plan for potential physiologic difficulty as is routinely done for anatomically difficulty airways. Optimization strategies to improve FPS-AE for patients with physiologically difficult airways should be studied in randomized controlled trials.

Introduction: Airway management in the critically ill is associated with a high prevalence of failed first attempts and adverse events which negatively impacts patient care. The purpose of this investigation is to describe an airway continuous quality improvement (CQI) program and its effect on the safety of rapid sequence intubation (RSI) in the emergency department (ED) over a 10-year period.Methods: An airway CQI program with an ongoing airway registry was initiated in our ED on July 1, 2007 (Academic Year 1) and continued through June 30, 2017 (Academic Year 10). Data were prospectively collected on all patients intubated in the ED during this period using a structured airway data collection form. Key data points included method of intubation, drugs and devices used for intubation, operator specialty and level of training, number of intubation attempts, and adverse events. Adult patients who underwent RSI in the ED with an initial intubation attempt by emergency medicine (EM) resident were included in the analysis. The primary outcome was first pass success which was defined as successful tracheal intubation with a single laryngoscope insertion. The secondary outcome was the prevalence of adverse events associated with intubation. Educational and clinical interventions were introduced throughout the study period with the goal of optimizing these outcomes. Data were analyzed by academic year and are reported descriptively with 95% confidence intervals (CI) of the difference of means.Results: EM residents performed RSI on 342 adult patients during Academic Year 1 and on 445 adult patients during Academic Year 10. Over the 10-year study period, first pass success increased from 73.1% to 92.4% (difference = 19.3%, 95% CI 14.0% to 24.6%). The percentage of patients who experienced an adverse event associated with intubation decreased from 22.5% to 14.4% (difference = -7.9%, 95% CI -13.4% to -2.4%). The percentage of patients with first pass success without an adverse event increased from 64.0% to 80.9% (difference = 16.9%, 95% CI 10.6% to 23.1%).Conclusion: The use of an airway CQI program with an ongoing airway registry resulted in a substantial improvement in the overall safety of RSI in the ED as evidenced by an increase in first pass success and a decrease in adverse events.

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research. [ABSTRACT FROM AUTHOR]

Introduction: Our objective is to evaluate the resident learning curves for direct laryngoscopy (DL) and GlideScope® video laryngoscopy (GVL) over the course of an emergency medicine (EM) residency training program.Methods: This was an analysis of intubations performed in the emergency department (ED) by EM residents over a seven-year period from July 1, 2007 to June 30, 2014 at an academic ED with 70,000 annual visits. After EM residents perform an intubation in the ED they complete a continuous quality improvement (CQI) form. Data collected includes patient demographics, operator post- graduate year (PGY), difficult airway characteristics (DACs), method of intubation, device used for intubation and outcome of each attempt. We included in this analysis only adult intubations performed by EM residents using a DL or a standard reusable GVL. The primary outcome was first pass success, defined as a successful intubation with a single laryngoscope insertion. First pass success was evaluated for each PGY of training for DL and GVL. Logistic mixed-effects models were constructed for each device to determine the effect of PGY level on first pass success, after adjusting for important confounders.Results: Over the seven-year period, the DL was used as the initial device on 1,035 patients and the GVL was used as the initial device on 578 patients by EM residents. When using the DL the first past success of PGY-1 residents was 69.9% (160/229; 95% CI 63.5%-75.7%), of PGY-2 residents was 71.7% (274/382; 95% CI 66.9%-76.2%), and of PGY-3 residents was 72.9% (309/424; 95% CI 68.4%-77.1%). When using the GVL the first pass success of PGY-1 residents was 74.4% (87/117; 95% CI 65.5%-82.0%), of PGY-2 residents was 83.6% (194/232; 95% CI 76.7%-87.7%), and of PGY-3 residents was 90.0% (206/229; 95% CI 85.3%-93.5%). In the mixed-effects model for DL, first pass success for PGY-2 and PGY-3 residents did not improve compared to PGY-1 residents (PGY-2 aOR 1.3, 95% CI 0.9-1.9; p-value 0.236) (PGY-3 aOR 1.5, 95% CI 1.0-2.2, p-value 0.067). However, in the model for GVL, first pass success for PGY-2 and PGY-3 residents improved compared to PGY-1 residents (PGY-2 aOR 2.1, 95% CI 1.1-3.8, p-value 0.021) (PGY-3 aOR 4.1, 95% CI 2.1-8.0, p

Background: Total hip and knee arthroplasties are common surgeries performed worldwide, but the management of pain during the subacute period (defined as hospital discharge to 3 months postoperatively) is poorly understood. This study aimed to determine patients' experiences, facilitators and barriers to subacute pain management following total hip or knee arthroplasty. Methods: Semi‐structured interviews with a purposive sample of patients following total hip or knee arthroplasty were conducted between June and August 2022. Participants were recruited from two tertiary metropolitan hospitals. Interviews were audio‐recorded and transcribed verbatim. Data were analysed using an inductive thematic approach to identify common themes. Results: In total, 30 interviews were conducted with patients following hip or knee arthroplasty. Four main themes were identified: (i) Physical constitution before surgery (joint condition, analgesic use, age, and hearing); (ii) Attitude and knowledge (motivation, outlook on life, attitude towards taking medications, individual benchmarking, and knowledge); (iii) Socio‐ethno‐cultural factors (family and community connection, language, and religion), and (iv) Health‐system support (health‐professional delivered education, medications, services, staff, and costs). Conclusions: Participants' experiences of subacute pain following hip or knee arthroplasty were shaped by multidimensional factors. Strategies to empower patients through increased education and support during postoperative opioid tapering as well as a shift to a biopsychosocial approach to pain management during the subacute period may improve patient and health‐system outcomes. [ABSTRACT FROM AUTHOR]