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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.

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.

Background: Surgical site infection (SSI) after liver transplant (LT) is common, but no studies have been conducted in Australia. The purpose of this study was to determine the proportion of patients who developed an SSI post‐LT in Australia's largest LT unit. Methods: This was a single‐center retrospective cohort study. We included all LT recipients who were aged 18 years or more and received their transplant between March 1, 2018 and April 1, 2023. The primary outcome was to determine the proportion of LT recipients who developed an SSI within 30 days of transplantation. Results: There were 404 LTs performed during the study period, and 375 met inclusion criteria. Of these, 8% (n = 31/375) developed an SSI and were classified as superficial (3%, n = 12/375) or deep/organ space (5%, n = 19/375). The most common antibiotics used for prophylaxis were amoxicillin/clavulanate (75%, n = 281/375), followed by piperacillin/tazobactam (17%, n = 62/375). Independent risk factors associated with the development of SSI were Roux‐en‐Y hepaticojejunostomy (aOR 3.16, 95% CI 1.17–8.28, p =.02), operative time (per 60‐min increment) (aOR 1.23, 95% CI 1.02–1.48), and re‐operation (aOR 4.16, 95% CI 1.81–9.58, p <.01). Type of antibiotic received perioperatively was not significantly associated with SSI. Conclusion: SSI occurred in 8% of LT recipients and was predominantly related to operation‐related factors rather than patient‐ or antibiotic‐related factors. [ABSTRACT FROM AUTHOR]

Background: Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia. Objectives: To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement. Methods: Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation. Results: We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3–77.9). Conclusion: We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol. [ABSTRACT FROM AUTHOR]

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]

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]