Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

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.).

Levels of Albumin and Impact on Loop Diuretic and Albumin Co-administration in Heart Failure.

ABSTRACT: Management of heart failure (HF) requires the use of loop diuretics to relieve congestion and improve symptoms. When loop diuretics alone fail to induce adequate diuresis, albumin has been proposed to enhance loop diuretic delivery and promote redistribution of fluid for excretion by the kidneys. Despite the theoretical benefits of albumin, studies suggesting its benefit in HF are scarce and the co-administration of loop diuretics and albumin remains controversial. This retrospective, observational study evaluated patients with HF 18 years or older who received concomitant intravenous loop diuretic and albumin administration. The primary objective was to evaluate the association of serum albumin level with urine output (UOP) in hospitalized patients with HF who received concomitant albumin and loop diuretic therapy. Secondary endpoints included total weight loss after 72 hours, and ICU and hospital lengths of stay. In total, 276 patients were included for analysis. There was no association between initial serum albumin level and 72-hour UOP (coefficient -623.1, 95% confidence interval -1558.6 to 312.4; P = 0.191) or weight difference at 72 hours (coefficient -1.0, 95% confidence interval -2.4 to 0.3; P = 0.131). Lower albumin levels were associated with longer ICU ( P = 0.034) and hospital ( P = 0.039) lengths of stay. Concomitant thiazide diuretic use and increasing loop diuretic doses were associated with increased 72-hour UOP. The results of our study suggests that providers should avoid using baseline albumin levels as guidance for albumin dosing in HF. Given the lack of comparator groups, larger randomized controlled trials should be done to provide a definitive role for albumin to enhance diuresis in patients with HF on intravenous loop diuretics.

Antibiotic De-Escalation Practices in the Intensive Care Unit: A Multicenter Observational Study.

BACKGROUND: There is little known about antibiotic de-escalation (ADE) practices in the intensive care unit (ICU). OBJECTIVE: The objective was to determine the proportion of patients who received ADE within 24 hours of actionable cultures and identify predictors of timely ADE. METHODS: Multicenter cohort study in ICUs of 15 hospitals in Australia and New Zealand. Adult patients were included if they were started on broad-spectrum antibiotics within 24 hours of ICU admission. The ADE was defined as switching from a broad-spectrum agent to a narrower-spectrum agent or antibiotic cessation. The primary outcome was ADE within 24 hours of an actionable culture, where ADE was possible. RESULTS: The 446 patients included in the study had a mean age of 63 ± 16 years, 60% were male, 32% were mechanically ventilated, and 19% were immunocompromised. Of these, 161 (36.1%) were not eligible for ADE and 37 (8.3%) for whom ADE within 24 hours of actionable culture could not be determined. In the remaining 248 patients, ADE occurred ≤24 hours in 60.5% (n = 150/248) after actionable cultures. In the multivariable logistic regression analysis, ADE was less likely to occur within 24 hours for patients with negative cultures (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.25-0.92, P = 0.03). CONCLUSION AND RELEVANCE: Timely ADE may not occur in 40% of patients in the ICU and is less likely to occur in patients with negative cultures. Timely ADE can be improved, and patients with negative cultures should be targeted as part of antimicrobial stewardship efforts.

Low rate of surgical site infections after liver transplantation: A 5-year retrospective cohort study.

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.

Finding individualised treatment in obese needing enoxaparin (FIT ONE): a multicentre study of therapeutic enoxaparin and the role of anti-factor Xa monitoring.

Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aim was to evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95 mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04 mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels (P = 0.135). Obesity was not included in the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95 mg/kg twice daily and 1.04 mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels.

A pilot multicentre randomised clinical trial to determine the effect of a pharmacist-partnered opioid tapering intervention before total hip or knee arthroplasty.

BACKGROUND: Opioid analgesic use before total hip or knee arthroplasty has been associated with worse postoperative outcomes. This pilot study aimed to examine the feasibility of a telehealth-based pharmacist-partnered opioid tapering intervention before elective primary hip or knee arthroplasty and its potential effectiveness compared with usual care. METHODS: This study was conducted at seven hospitals in New South Wales, Australia. Eligible patients were those aged ≥ 18 years, scheduled to undergo primary hip or knee arthroplasty for osteoarthritis and taking opioid analgesics pre-operatively. The intervention group participated in an opioid tapering telehealth service, a partnership between a pharmacist and general practitioner, for 3 months pre-operatively up to the day of surgery, while the control group received usual care. The primary outcomes of the study were to investigate the feasibility of the intervention (i.e. adherence to treatment) and potential effectiveness in decreasing baseline daily opioid dose by > 50% before surgery. RESULTS: Between December 2021 and June 2023, 70 patients were recruited and assigned randomly to the intervention group (n = 35) or control group (n = 35). Baseline characteristics were similar between groups. Thirty patients in each group completed their allocated treatment. All patients allocated to the intervention group completed at least one appointment with a pharmacist, with the median (IQR [range]) being 2 (1-4 [1-6]) appointments. The number of patients who successfully decreased their baseline daily opioid dose by ≥ 50% before surgery was 27/30 in the intervention group compared with 5/30 in the usual care group (p < 0.001). CONCLUSIONS: The findings of this pilot study support the feasibility of a telehealth-delivered, pharmacist-partnered opioid tapering service for patients scheduled for primary hip or knee arthroplasty. A broader multicentre study to examine the effectiveness of this intervention on clinical outcomes is warranted.

Effectiveness of Sublingual Buprenorphine for Pain Control in the ICU.

OBJECTIVES: The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone oral/enteral during ICU admission. DESIGN: This was a retrospective, parallel, cohort study. SETTING: General medical or surgical ICUs of a quaternary, urban hospital in Sydney, NSW, Australia. PATIENTS: Data were obtained for all patients admitted to two general medical or surgical ICU from January 2019 to January 2023. Patients were grouped as those who received buprenorphine sublingual versus oxycodone oral/enteral. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pain control was compared between a propensity score matched cohort of patients who received buprenorphine versus oxycodone. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0-10 Numeric Rating Scale or greater than or equal to 6 on the Behavioral Pain Scale. The study cohort included 1,070 patients (288 buprenorphine and 782 oxycodone). After propensity score matching, there were 288 patients in each group. The mean age of the matched cohort was 64 ± 16 years, 295 (51%) were male, and 359 (62%) had a surgical admission. The median probability of significant pain was 0.16 with buprenorphine and 0.17 with oxycodone (median difference, 0.01; 95% CI, -0.02 to 0.04; p = 0.50). Median opioid consumption in oral morphine milligram equivalents (MMEs) was 65 with buprenorphine and 70 with oxycodone (median difference, -1 mg; 95% CI, -10 to 10 mg; p = 0.73). Median MME per ICU day was 22 with buprenorphine and 22 with oxycodone (median difference, 1 mg; 95% CI, -2 to 5 mg; p = 0.38). CONCLUSIONS: Buprenorphine sublingual is as effective as oxycodone oral/enteral with regard to pain control and opioid consumption in the ICU. Buprenorphine sublingual is an appropriate option for patients in the ICU who are unable to take oral/enteral medications.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Effectiveness of organizational interventions on appropriate opioid prescribing for noncancer pain upon hospital discharge: A systematic review.

This study aims to summarize the effectiveness of organizational interventions on appropriate opioid prescribing for noncancer pain upon hospital discharge. A systematic search was conducted on 6 electronic databases by 2 independent reviewers. We included original research articles reporting on quantitative outcomes of organizational interventions targeting appropriate opioid prescribing on hospital discharge. Quality assessment was performed by 2 independent reviewers. The protocol for this review was prospectively registered on PROSPERO (ID: CRD42020156104). Out of 173 full texts assessed for eligibility, 43 were included in this review. The majority of studies had a moderate to serious risk of bias (33 out of 43). Most of the studies implemented a multifaceted organizational intervention (16 studies). Other interventions included guideline implementation, prescriber education and default opioid-prescribing quantity changes in electronic medical records. Multiple studies found that the dissemination of patient-specific and procedure-specific guidelines reduced the quantity of opioids prescribed by 44 to 57%. Prescriber education provided with feedback was implemented in 4 studies and resulted in a 33 to 44% decrease in prescribing rates. Lowering the default quantities in the electronic medical records produced a 40% decrease in opioids prescribed in 1 study. Guideline implementation, prescriber education and default opioid-prescribing quantity changes all appear effective in improving the appropriate prescribing of opioids on hospital discharge. However, the extent of reduction of opioid prescribing upon hospital discharge after the implementation of multifaceted intervention strategies appears similar to that of simpler interventions which require fewer resources.

Preventability of venous thromboembolism in hospitalised patients.

BACKGROUND: Hospital-acquired venous thromboembolism (VTE) is a major cause of morbidity and mortality. AIMS: To determine the proportion of patients with hospital-acquired VTE that are preventable. METHODS: This was a retrospective study of patients in two tertiary care hospitals in Sydney, Australia. Data were collected for patients with hospital-acquired VTE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) coding from January 2018 to May 2020. Patients were classified as low, moderate or high risk of developing a VTE during hospitalisation based on demographic and clinical factors. A hospital-acquired VTE was considered to be potentially preventable if there was suboptimal prophylaxis in the absence of contraindications. Suboptimal therapy included at least one of the following related to VTE prophylaxis: low dose, missed dose (prior to developing a VTE), suboptimal drug and delayed start (>24 h from admission). RESULTS: There were 229 patients identified with VTE based on ICD-10-AM coding. A subset of 135 patients were determined to have actual hospital-acquired VTE. Of these, there were no patients at low risk, 64% (87/135) at moderate risk and 44% (48/135) at high risk of developing a VTE. Most (65%; n = 88/135) patients had one or more contraindications to receive recommended prophylaxis. Overall, the proportion of patients who received suboptimal prophylaxis was 11% (15/135). CONCLUSION: Approximately one out of 10 hospital-acquired VTE are preventable. Hospitals should focus on measuring and reporting VTE that are preventable to provide a more accurate measure of the burden of VTE that can be reduced by improving care.

Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain : A Systematic Review and Meta-analysis.

BACKGROUND: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain. PURPOSE: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting. DATA SOURCES: Electronic databases and registries from inception to 7 February 2022. STUDY SELECTION: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED. DATA EXTRACTION: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. DATA SYNTHESIS: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics. LIMITATIONS: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes. CONCLUSION: The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42021275293).

The Pediatric Rigid Stylet Improves First-Pass Success Compared With the Standard Malleable Stylet and Tracheal Tube Introducer in a Simulated Pediatric Emergency Intubation.

BACKGROUND: Pediatric emergency intubation is a high-acuity, low-occurrence procedure. Despite advances in technology, the success of this procedure remains low and adverse events are very high. Prospective observational studies in children have demonstrated improved success with the use of video laryngoscopy (VL) compared with direct laryngoscopy, although reported first-pass success (FPS) rates are lower than that reported for adults. This may in part be due to difficulty directing the tracheal tube to the laryngeal inlet considering the cephalad position of the larynx in infants. Using airway adjuncts such as the pediatric rigid stylet (PRS) or a tracheal tube introducer (TTI) may aid with intubation to the cephalad positioned airway when performing VL. The objectives of this study were to assess the FPS and time to intubation when intubating an infant manikin with a standard malleable stylet (SMS) compared with a PRS and TTI. METHODS: This was a randomized cross-over study performed at an academic institution both with emergency medicine (EM) and combined pediatric and EM (EM&PEDS) residency programs. Emergency medicine and EM&PEDS residents were recruited to participate. Each resident performed intubations on a 6-month-old infant simulator using a standard geometry C-MAC Miller 1 video laryngoscope and 3 different intubation adjuncts (SMS, PRS, TTI) in a randomized fashion. All sessions were video recorded for data analysis. The primary outcome was FPS using the 3 different intubation adjuncts. The secondary outcome was the mean time to intubation (in seconds) for each adjunct. RESULTS: Fifty-one participants performed 227 intubations. First-pass success with the SMS was 73% (37/51), FPS was 94% (48/51) with the PRS, and 29% (15/51) with the TTI. First-pass success was lower with the SMS (-43%; 95% confidence interval [CI], -63% to -23%; P < 0.01) and significantly lower with the TTI compared with PRS (difference -65%; 95% CI, -81% to -49%; P < 0.01). First-pass success while using the PRS was higher than SMS (difference 22%, 7% to 36%; P < 0.01). The mean time to intubation using the SMS was 44 ± 13 seconds, the PRS was 38 ± 11 seconds, and TTI was 59 ± 15 seconds. The mean time to intubation was higher with SMS (difference 15 seconds; 95% CI, 10 to 20 seconds; P < 0.01) and significantly higher with the TTI compared with PRS (difference 21 seconds; 95% CI, 17 to 26 seconds; P < 0.01). Time to intubation with the PRS was lower than SMS (difference -7 seconds; 95% CI, -11 to -2 seconds; P < 0.01). The ease of use was significantly higher for the PRS compared with the TTI when operators rated them on a visual analog scale (91 vs 20 mm). CONCLUSIONS: Use of the PRS by EM and EM&PEDS residents on an infant simulator was associated with increased FPS and shorter time to intubation. Clinical studies are warranted comparing these intubation aids in children.

Dose equivalence between metaraminol and norepinephrine in critical care.

AIMS: The aim of this study was to determine the conversion dose ratio between continuous infusion metaraminol and norepinephrine in critically ill patients with shock. METHODS: A retrospective cohort study was conducted in adult patients with shock admitted to an intensive care unit from 29 October 2018 to 30 October 2019 and who transitioned from metaraminol monotherapy to norepinephrine monotherapy. Mean arterial pressure (MAP) and infusion doses for both drugs were collected at hourly intervals; 2 hours before to 5 hours after switching from metaraminol monotherapy to norepinephrine monotherapy. The conversion dose ratio was defined as the ratio of metaraminol (µg.kg-1 .min-1) : norepinephrine (µg.kg-1 .min-1 ) required to achieve a similar MAP. RESULTS: A total of 43 out of 144 eligible patients were included. The median age was 68 years (IQR 56-76) and 22 (51%) were male. There was no significant difference between the baseline MAP during metaraminol monotherapy (median 71 mm Hg, IQR 66-76) and the post-transition MAP during norepinephrine monotherapy (median 70 mm Hg, IQR 66-73) (P = .09). The median conversion dose ratio between metaraminol and norepinephrine was 13 (IQR 7-24). In the sensitivity analyses, the median conversion dose ratio using the maximum and the mean norepinephrine infusion dose was 8 (IQR 5-16) and 12 (IQR 8-23), respectively. CONCLUSION: A conversion dose ratio of 10:1 (metaraminol µg.kg-1 .min-1 :norepinephrine µg.kg-1 .min-1 ) may be used in critically ill patients with shock to account for ease of calculations and variability of the conversion ratio in the primary and sensitivity analyses.

Intravenous to Oral Transition of Amiodarone (IOTA): Effect of Various Durations of Overlap on Atrial Fibrillation Recurrence After Cardiothoracic Surgery.

ABSTRACT: The use of amiodarone for postoperative atrial fibrillation (AF) is widespread; however, there is a paucity of data on the optimal duration of overlap when transitioning from intravenous (IV) to oral amiodarone. The objective of this study was to evaluate the safety and efficacy of varying durations of overlap when amiodarone IV infusion is transitioned to oral administration in cardiothoracic surgery patients. This retrospective, observational, single-center study included cardiothoracic surgery patients who were initiated on IV amiodarone for supraventricular arrhythmia and subsequently transitioned to oral amiodarone. The primary outcome was AF recurrence within 24 hours after IV amiodarone discontinuation. Safety outcomes include occurrence of bradycardia or hypotension while on amiodarone. A total of 184 patients were included for analysis. AF recurrence occurred in 24.5% of patients (n = 45). No significant association was found between various overlap durations and AF recurrence (odds ratio (OR) 1.00, 95% CI 1.00-1.01, P = 0.9). In addition, no significant association was found between duration of overlap and rates of bradycardia (OR 1.00, 95% confidence interval (CI) 0.99-1.00, P = 0.08) or hypotension (OR 1.00, 95% CI 0.99-1.00, P = 0.21), which occurred in 35.9% and 47.3% of patients, respectively. Our study suggests following conversion to normal sinus rhythm; cardiothoracic surgery patients can effectively and safely be transitioned from IV to oral amiodarone without the need for specific overlap duration or transition strategy.

Effectiveness of Pharmacological-Based Interventions, Including Education and Prescribing Strategies, to Reduce Subacute Pain After Total Hip or Knee Arthroplasty: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) surgeries are among the most common elective procedures. Moderate to severe postoperative pain during the subacute period (defined here as the period from hospital discharge to 3 months postoperatively) is a predictor of persistent pain 12 months postoperatively. This review aimed to examine the available postdischarge pharmacological interventions, including educational and prescribing strategies, and their effect on reducing pain during the subacute period after TKA or THA. METHODS: We searched seven electronic databases from inception to April 22, 2021. Published randomized controlled trials of adults who underwent TKA or THA and received a pharmacological-based intervention commencing within 1 week after hospital discharge and conducted for up to 3 months postoperatively were compared with any treatment. Two reviewers independently extracted data on the primary outcome, pain intensity. This review was registered prospectively on PROSPERO (ID: CRD42021250384). RESULTS: Four trials involving 660 participants were included. Interventions included changing analgesic prescribing practices upon hospital discharge and education on analgesic use. Providing multimodal non-opioid analgesia in addition to reduced opioid quantity was associated with lower subacute pain (coefficient -0.81; 95% confidence interval -1.33 to -0.29; P = 0.003). Education on analgesic use during multidisciplinary home visits was effective for reducing pain intensity during the subacute period (6.25 ± 10.13 vs 35.67 ± 22.05; P < 0.001) compared with usual care. CONCLUSIONS: Interventions involving the provision of multimodal non-opioid analgesia and education on analgesic use show positive effects on reducing pain intensity during the subacute period after TKA and THA.

Pharmacogenomic testing: perception of clinical utility, enablers and barriers to adoption in Australian hospitals.

BACKGROUND: Despite healthcare professionals (HCP) endorsing the clinical utility of pharmacogenomics testing, use in clinical practice is limited. AIMS: To assess HCP' perceptions of pharmacogenomic testing and identify barriers to implementation. METHODS: HCP involved in prescribing decisions at three hospitals in Sydney, Australia, were invited to participate. The online survey assessed perceptions of pharmacogenomic testing, including: (i) demographic and practice variables; (ii) use, knowledge and confidence; (iii) perceived benefits; (iv) barriers to implementation; and (v) operational and/or system changes and personnel required to implement on site. RESULTS: HCP were predominantly medical practitioners (75/107) and pharmacists (25/107). HCP perceived pharmacogenomic testing was beneficial to identify reasons for drug intolerance (85/95) and risk of side-effects (86/95). Although testing was considered relevant to their practice (79/100), few HCP (23/100) reported past or intended future use (26/100). Few HCP reported confidence in their ability to identify indications for pharmacogenomic testing (14/107), order tests (19/106) and communicate results with patients (16/107). Lack of clinical practice guidelines (62/79) and knowledge (54/77) were identified as major barriers to implementation of pharmacogenomics. Comprehensive reimbursement for testing and clinical practice guidelines, alongside models-of-care involving multidisciplinary teams and local clinical champions were suggested as strategies to facilitate implementation of pharmacogenomic testing into practice. CONCLUSIONS: Pharmacogenomic testing was considered important to guide drug selection and dosing decisions. However, limited knowledge, low confidence and an absence of guidelines impede the use of pharmacogenomic testing. Establishment of local resources including multidisciplinary models-of-care was suggested to facilitate implementation of pharmacogenomics.

Intubation During Pediatric Cardiac Arrest in the Emergency Department Is Associated With Reduced First-Pass Success.

BACKGROUND: Airway compromise and respiratory failure are leading causes of pediatric cardiac arrest making advanced airway management central to pediatric resuscitation. Previous literature has demonstrated that achieving first-pass success (FPS) is associated with fewer adverse events. In cardiac arrest for adult patients, increasing number of intubation attempts is associated with lower likelihood of return of spontaneous circulation (ROSC) and favorable neurologic outcome. There is limited evidence regarding advanced airway management for pediatric out-of-hospital cardiac arrest (OHCA) in the emergency department (ED). The purpose of this study was to compare FPS in pediatric OHCA and non-cardiac arrest patients in the ED. METHODS: This is an analysis of pediatric intubations prospectively recorded into a continuous quality improvement database in an academic pediatric ED over a 12-year period. Between July 1, 2007, and June 30, 2019, physicians recorded all intubations performed in the pediatric ED. The database included patient demographics and detailed information about each intubation such as age of the patient, reason for intubation, number of intubation attempts, and outcome of each attempt. All patients younger than 18 years who underwent intubation in the ED were eligible for inclusion in the study. The primary outcome was FPS for pediatric patients in cardiac arrest compared with those not in cardiac arrest. A logistic regressions analysis was performed to identify characteristics associated with FPS in OHCA patients. RESULTS: Six hundred eight pediatric patients were intubated during the study period. One hundred three pediatric patients had OHCA compared with 459 non-cardiac arrest patients who underwent rapid sequence intubation. In patients with OHCA, 47.6% had FPS (95% confidence interval [CI], 38.2%-57.1%), 33% required 2 attempts (95% CI, 24.7%-42.6%), and 19.4% required 3 or more attempts (95% CI, 12.9%-28.2%). In patients without OHCA, 75.4% had FPS (95% CI, 75.4%-79.1%), 15% required 2 attempts (95% CI, 12.0%-18.6%), and 9.6% required 3 or more attempts (95% CI, 7.2%-12.6%). Cardiac arrest was associated with a reduction in FPS adjusted odds ratio 0.44 (95% CI, 0.26-0.77). CONCLUSIONS: In this study, we found that pediatric OHCA is associated with reduced FPS in the ED. Although additional studies are needed, rescuers should prioritize restoring effective oxygenation and ventilation and optimizing intubation conditions before an advanced airway attempt.

Predictive Performance of Bayesian Vancomycin Monitoring in the Critically Ill.

OBJECTIVES: It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill. DESIGN: Retrospective cohort study. SETTING: Single-center ICU. PATIENTS: Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the sd of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (-1.7 to 1.8 mg/L), which was lower with a posteriori estimate (-0.7 to 1.8 mg/L). However, all three models showed low precision in terms of sd (4.7-8.8 mg/L) and root mean square error (4.8-8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7-3.2 mg/L for < 20 mg/L; -5.1 to -2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations. CONCLUSIONS: Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously.

Can Emergency Medical Services Utilization Rates Be Used to Measure the Success of An Alcohol Amnesty Policy?

INTRODUCTION: Medical Amnesty/Good Samaritan (MAGS) policies, which eliminate legal charges when students call 9-1-1 for excessive drinking, have been implemented with the goal of reducing barriers to accessing Emergency Medical Services (EMS). This study investigated the impact of MAGS policy implementation on EMS calls on campus and if that EMS call volume could be used to measure policy success. The aim of this study was to compare the prevalence of alcohol-related EMS calls before and after MAGS implementation at a single large public university campus. Methods: A retrospective review of all 9-1-1 calls to on-campus locations was conducted using patient care records (PCRs) from a collegiate EMS agency responding exclusively to on-campus 9-1-1 calls. Calls were excluded if the PCR was marked "incomplete", were outside the 2015 CBEMS response zone boundaries, or if patient age was <15 or >25 years old to ensure analysis was targeting the on-campus student population. The incidence of alcohol-related 9-1-1 calls was compared between one academic year (AY) prior to (pre-MAGS, AY2015) and two years after MAGS implementation (post-MAGS, AY2016/17). An alcohol-related 9-1-1 call was defined as an EMS provider primary or secondary impression of "Alcohol, Alcohol Intoxication, or Alcohol Ingestion" or a call in which the patient explicitly admitted to alcohol use. Relative risk (RR) with 95% confidence intervals (CI) were used to describe the results. Results: Over the three-year study period, the collegiate EMS agency responded to 2440 calls of which 1283 met inclusion criteria. 58 calls were excluded for being incomplete, 227 were outside the original boundaries and 872 were outside the defined age range. Of those calls, 351 were pre-MAGS and 932 were post-MAGS. Of the total 9-1-1 calls, 127 (36.2%) were related to alcohol pre-MAGS and 327 (35.1%) were related to alcohol post-MAGS policy implementation. The relative risk of a 9-1-1 call being made for alcohol-related issues after MAGS implementation was RR = 0.97 (95% CI 0.83-1.14; P = 0.713). Conclusion: Implementation of a MAGS policy was not associated with a significant change in the number of alcohol-related EMS responses. It is unclear if these results reflect ineffective policy implementation or a general reduction in on-campus alcohol consumption. However, using EMS call volume as a marker for policy success and quality improvement offers an innovative tool through which EMS agencies can provide valuable feedback to other system stakeholders.

Can ultrasound novices develop image acquisition skills after reviewing online ultrasound modules?

BACKGROUND: Point-of-care ultrasound is becoming a ubiquitous diagnostic tool, and there has been increasing interest to teach novice practitioners. One of the challenges is the scarcity of qualified instructors, and with COVID-19, another challenge is the difficulty with social distancing between learners and educators. The purpose of our study was to determine if ultrasound-naïve operators can learn ultrasound techniques and develop the psychomotor skills to acquire ultrasound images after reviewing SonoSim® online modules. METHODS: This was a prospective study evaluating first-year medical students. Medical students were asked to complete four SonoSim® online modules (aorta/IVC, cardiac, renal, and superficial). They were subsequently asked to perform ultrasound examinations on standardized patients utilizing the learned techniques/skills in the online modules. Emergency Ultrasound-trained physicians evaluated medical students' sonographic skills in image acquisition quality, image acquisition difficulty, and overall performance. Data are presented as means and percentages with standard deviation. All P values are based on 2-tailed tests of significance. RESULTS: Total of 44 medical students participated in the study. All (100%) students completed the hands-on skills evaluation with a median score of 83.7% (IQR 76.7-88.4%). Thirty-three medical students completed all the online modules and quizzes with median score of 87.5% (IQR 83.8-91.3%). There was a positive association between module quiz performance and the hands-on skills performance (R-squared = 0.45; p < 0.001). There was no statistically significant association between module performance and hands-on performance for any of the four categories individually. In all four categories, the evaluators' observation of the medical students' difficulty obtaining views correlated with hands-on performance scores. CONCLUSIONS: Our study findings suggest that ultrasound-naïve medical students can develop basic hands-on skills in image acquisition after reviewing online modules.