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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., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. Crown.)

Background: National Personal Health Records (PHRs) have been proposed to improve the transfer of medication-related information during transition of care. Objective: To evaluate the concordance between the medications captured in the Australian national PHR, My Health Record (MyHR), and the pharmacist obtained best possible medication history (BPMH) for patients upon hospital admission. Method: This prospective observational study used a convenience sample of hospital patients. For newly admitted patients, the investigating pharmacist obtained a BPMH and then compared it to the medication list captured in MyHR. Upon comparison, the medications were categorised into either complete match, partial match or mismatch. Medications with a complete or partial match were grouped together. Medications with deviations were then assessed for risk based on their potential consequence, and reported descriptively. A multivariable logistic regression was conducted to assess the factors associated with a drug being mismatched. Results: A total of 82 patients were recruited, with a cumulative total of 1,207 medications documented. Of the 1,207 medications, 714 (59.2%) medications were documented as a complete/partial match. The remaining 493 (40.8%) medications were mismatched. Of the 493 mismatched medications, 442 (89.7%) were deemed low-risk deviations and 51 (10.3%) were deemed high-risk. A medication was more likely to be mismatched, rather than completely/partially matched, if it was a regular non-prescription medication, or "when-required" prescription medication, or "when required" non-prescription medication, or if it was administered parenterally. Conclusion: National PHRs may be a secondary source to either confirm a patient's medication history or be used as a starting point for a BPMH., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

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., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

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., (© 2024. The Author(s).)

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.

Background: Few Australian studies have examined the incidence of prescribed opioid use prior to primary total knee or total hip arthroplasty (TKA, THA) and whether it predicts post-surgery outcomes. A recent Australian study demonstrated that the prevalence of pre-arthroplasty opioid use was approximately 16%. In the United States, approximately 24% of people undergoing TKA or THA are chronic opioid users preoperatively., Purpose: This study aimed to determine (i) the proportion of TKA and THA patients who use prescribed opioids regularly (daily) before surgery (i.e., opioid use reported between the time of waitlisting and any time up to 3 months before surgery), (ii) if opioid use before surgery predicts (a) complication/readmission rates to 6-months post-surgery, and (b) patient-reported outcomes to 6-months post-surgery., Methods: A retrospective cohort study of patients who underwent TKA or THA between January 2013 and June 2018 from two Australian public hospitals was undertaken utilizing linked individual patient-level data from two prospectively collected independent databases comprising approximately 3,500 and 9,500 people (database contained known opioid usage data within the 5-year time frame). Inclusion criteria included (i) primary diagnosis of osteoarthritis of the index joint, (ii) primary elective THA or TKA, and (iii) age ≥ 18 years. Exclusion criteria included (i) revision arthroplasty, (ii) non-elective arthroplasty, (iii) hip hemiarthroplasty, (iv) uni-compartmental knee arthroplasty, and (v) previous unilateral high tibial osteotomy., Results: Analysis was completed on 1,187 study participants (64% female, 69% TKA, mean (SD) age 67 [9.9]). 30% were using regular opioids preoperatively. Adjusted regression analyses controlling for multiple co-variates indicated no significant association between preoperative opioid use and complications/readmission rates or patient-reported outcomes to 6 months post-surgery. Model diagnostics produced poor discrimination for area under the curves and non-significant goodness of fit tests. Pre-arthroplasty opioid use was associated with lower health-related quality of life (EuroQol-Visual Analogue Scale) compared to non-opioid users undergoing primary THA (mean difference -5.04 [-9.87, -0.22], P = 0.04, Adjusted R 2 = 0.06) CONCLUSION: In this study, 30% of patients were using prescribed opioids daily prior to primary TKA or THA. Pre-arthroplasty opioid use was not associated with postoperative adverse events or patient-reported pain, function, or global perceived improvement up to six months post-surgery., (© 2024. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI -.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1-201] vs 4 [range 1-226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PERSPECTIVE: This study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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., (© 2023 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Purpose: The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult patients. Secondary objectives were to describe how norepinephrine is used such as the maximum duration, infusion rate and concentration, and to determine the most common first-line PVI used by country., Materials and Methods: An international multi-centre cross-sectional survey study was conducted in adult intensive care units in Australia, US, UK, Canada, and Saudi Arabia., Results: Critical care pharmacists from 132 institutions responded to the survey. Norepinephrine PVIs were utilised in 86% of institutions (n = 113/132). The median maximum duration of norepinephrine PVIs was 24 h (IQR 24-24) (n = 57/113). The most common maximum norepinephrine PVI rate was between 11 and 20 μg/min (n = 16/113). The most common maximum norepinephrine PVI concentration was 16 μg/mL (n = 60/113). Half of the institutions had a preference to administer another PVI over norepinephrine as a first-line agent (n = 66/132). The most common alternative PVI used by country was: US (phenylephrine 41%, n = 37/90), Canada (dopamine 31%, n = 5/16), UK (metaraminol 82%, n = 9/11), and Australia (metaraminol 89%, n = 8/9)., Conclusions: There is variability in clinical practice regarding PVI administration in critically ill adult patients dependent on drug availability and local institutional recommendations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of TBUP compared to other analgesics or placebo for acute postoperative pain. A systematic search was conducted using Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) until December 26, 2022. The search included randomized controlled trials comparing TBUP versus other analgesics or placebo for acute postoperative pain. A certainty assessment was conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The protocol for this review was registered on Prospective Register of Systematic Reviews (CRD42022318601). In total, 15 studies involving 1,205 participants were included that compared TBUP versus fentanyl (n = 2), celecoxib (n = 3), placebo (n = 2), tramadol (n = 5), diclofenac (n = 3), parecoxib (n = 1), and flurbiprofen (n = 1). Meta-analyses were conducted for 3 comparators that involved 2 studies each. There was no significant difference in pain between TBUP 10 mcg/h versus fentanyl 25 mcg/h (standardized mean difference [SMD] -.03, 95% confidence interval [CI] -.86 to .81, P = .95, I 2 = 85%). TBUP 10 mcg/h was associated with less pain compared to celecoxib 200 mg twice daily (SMD -.32, 95% CI -.58 to -.05, P = .02, I 2 = 0%) and placebo (SMD -2.29, 95% CI -4.32 to -.27, P = .03, I 2 = 94%). The GRADE assessment showed a very low certainty of evidence for all comparisons. There is insufficient evidence that TBUP improves pain control compared to other analgesics for acute postoperative pain. PERSPECTIVE: This systematic review and meta-analysis compared the use of TBUP to other analgesics for postoperative pain. The results showed that there is insufficient evidence to recommend the use of TBUP in this setting. The findings will help clinicians select the most appropriate opioid regimens for postoperative pain., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Dr. Mosier is currently the National Course Director for the Difficult Airway Course: Critical Care. Dr. Heffner received funding as an advisor/speaker. Drs. Mosier, Hirsch, Heffner, and Gunnerson have served as expert witness. The remaining authors have disclosed that they do not have any potential conflicts of interest. 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., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Mosier is currently the National Course Director for the Difficult Airway Course: Critical Care. Dr. Heffner received funding as an advisor/speaker. Drs. Mosier, Hirsch, Heffner, and Gunnerson have served as expert witnesses. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Purpose: To provide key pharmacological concepts underlying drug-drug interactions (DDIs), a decision-making framework, and a list of DDIs that should be considered in the context of contemporary acutely ill patients with COVID-19., Summary: DDIs are frequently encountered in the acutely ill. The implications of DDIs include either increased risk of drug toxicity or decreased effectiveness, which may have severe consequences in the acutely ill due to lower physiological and neurocognitive reserves in these patients. In addition, an array of additional therapies and drug classes have been used for COVID-19 that were not typically used in the acute care setting. In this update on DDIs in the acutely ill, we provide key pharmacological concepts underlying DDIs, including a discussion of the gastric environment, the cytochrome P-450 (CYP) isozyme system, transporters, and pharmacodynamics in relation to DDIs. We also provide a decision-making framework that elucidates the identification of DDIs, risk assessment, selection of alternative therapies, and monitoring. Finally, important DDIs pertaining to contemporary acute care clinical practice related to COVID-19 are discussed., Conclusion: Interpreting and managing DDIs should follow a pharmacologically based approach and a systematic decision-making process to optimize patient outcomes., (© American Society of Health-System Pharmacists 2023.)

Opioid analgesics are commonly used by patients awaiting orthopaedic surgery, and preoperative opioid use is associated with a greater burden of postoperative pain, suboptimal surgical outcomes and higher healthcare costs. This study aimed to examine the prevalence of total opioid use before elective orthopaedic surgery with a focus on regional and rural hospitals in New South Wales, Australia. This was a cross-sectional, observational study of patients undergoing orthopaedic surgery conducted between April 2017 and November 2019 across five hospitals that included a mix of metropolitan, regional, rural, private and public settings. Preoperative patient demographics, pain scores and analgesic use were collected during pre-admission clinic visits, held between two and six weeks before surgery. Of the 430 patients included, 229 (53.3%) were women and the mean age was 67.5 (standard deviation 10.1) years. The overall prevalence of total preoperative opioid use was 37.7% (162/430). Rates of preoperative opioid use ranged from 20.6% (13/63) at a metropolitan hospital to 48.8% (21/43) at an inner regional hospital. Multivariable logistic regression showed that the inner regional setting was a significant predictor of opioid use before orthopaedic surgery (adjusted odds ratio 2.6; 95% confidence interval 1.0 to 6.7) after adjusting for covariates. Opioid use prior to orthopaedic surgery is common and appears to vary by geographical location.

Opioid analgesics prescribed for the management of acute pain following orthopaedic surgery may lead to unintended long-term opioid use and associated patient harms. This study aimed to examine the prevalence of opioid use at 90 days after elective orthopaedic surgery across major city, regional and rural locations in New South Wales, Australia. We conducted a prospective, observational cohort study of patients undergoing elective orthopaedic surgery at five hospitals from major city, regional, rural, public and private settings between April 2017 and February 2020. Data were collected by patient questionnaire at the pre-admission clinic 2-6 weeks before surgery and by telephone call after 90 days following surgery. Of the 361 participants recruited, 54% (195/361) were women and the mean age was 67.7 years (standard deviation 10.1 years). Opioid use at 90 or more days after orthopaedic surgery was reported by 15.8% (57/361; 95% confidence interval (CI) 12.2-20%) of all participants and ranged from 3.5% (2/57) at a major city location to 37.8% (14/37) at an inner regional location. Predictors of long-term postoperative opioid use in the multivariable analysis were surgery performed at an inner regional location (adjusted odds ratio 12.26; 95% CI 2.2-68.24) and outer regional location (adjusted odds ratio 5.46; 95% CI 1.09-27.50) after adjusting for known covariates. Long-term opioid use was reported in over 15% of patients following orthopaedic surgery and appears to be more prevalent in regional locations in Australia.

Background: Medication reconciliation is an effective strategy to reduce medication errors upon hospital admission. The process involves obtaining a best possible medication history (BPMH), which can be both time-consuming and resource-intensive. During the COVID-19 pandemic, telepharmacy was used to reduce the risk of viral transmission. Telepharmacy is the remote provision of pharmacy-led clinical services, such as obtaining BPMHs, using telecommunications. However, the accuracy of telephone-obtained BPMHs has not yet been evaluated. Therefore, the primary aim of this study was to evaluate the proportion of patients who have an accurate BPMH from the telephone-obtained BPMH compared to an in-person obtained BPMH., Methods: This prospective, observational study took place in a large tertiary hospital. Recruited patients or carers had their BPMH obtained by a pharmacist over the telephone. The same patients or carers then had their BPMH conducted in-person to identify any deviations between the telephone-obtained and in-person obtained BPMH. All telephone-obtained BPMHs were timed with a stopwatch. Any deviations were categorised according to their potential consequence. An accurate BPMH was defined as having no deviations. Descriptive statistics were used to report all quantitative variables. A multivariable logistic regression was conducted to identify risk factors for patients and medications for having medication deviations., Results: In total, 116 patients were recruited to receive both a telephone-obtained and in-person obtained BPMH. Of these, 91 patients (78%) had an accurate BPMH with no deviations. Of the 1104 medications documented across all the BPMHs, 1064 (96%) had no deviation. Of the 40 (4%) medication deviations, 38 were deemed low-risk (3%) and 2 high-risk (1%). A patient was more likely to have a deviation if they are taking more medications (aOR: 1.11; 95% CI: 1.01-1.22; p < 0.05). A medication was more likely to have a deviation if it was regular non-prescription medication (aOR: 4.82; 95% CI: 2.14-10.82; p < 0.001) or 'when required' non-prescription medication (aOR: 3.12; 95% CI: 1.20-8.11; p = 0.02) or a topical medication (aOR: 12.53; 95% CI: 4.34-42.17; p < 0.001)., Conclusions: Telepharmacy represents a reliable and time-efficient alternative to in-person BPMHs., (© 2023. Crown.)

Background: Medication-related hospitalisations present an opportunity for de-prescribing and simplification of medication regimens. The Medication Regimen Complexity Index (MRCI) is a tool for measuring the complexity of medication regimens., Objectives: To evaluate whether MRCI changes following medication-related hospitalisations, and to evaluate the relationship between MRCI, length of stay (LOS) in hospital, and patient characteristics., Methods: A retrospective medical record review of patients admitted to a tertiary referral hospital in Australia for medication-related problems, January 2019 to August 2020. MRCI was calculated using pre-admission medication lists and discharge medication lists., Results: There were 125 patients who met inclusion criteria. The median (IQR) age was 64.0 years (45.0-75.0) and 46.4% were female. Median MRCI decreased by 2.0 following hospitalisation: from median (IQR) 17.0 (7.0-34.5) on admission vs 15.0 (3.0-29.0) on discharge (p < 0.001). Admission MRCI predicted LOS ≥2 days (OR 1.03, 95%CI 1.00-1.05, p = 0.022). Allergic reaction-related hospitalisations were associated with lower admission MRCI., Conclusions: There was a decrease in MRCI following medication-related hospitalisation. Targeted medication reviews for high-risk patients (e.g., those with medication-related hospitalisations) could further reduce the burden of medication complexity following discharge from hospital and possibly prevent readmissions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Linezolid is a broad-spectrum antimicrobial with limited use due to toxicity. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM)., Methods: Patients administered linezolid between January 2017 and December 2019 were retrospectively reviewed. Data were collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between those who did and did not experience linezolid toxicity. A multivariable logistic regression model was constructed to identify any covariates that correlated with toxicity., Results: Linezolid was administered to 1050 patients; of these, 381 did not meet the inclusion criteria and 47 were excluded as therapy ceased for non-toxicity reasons. There were 105 of 622 (16.9%) patients assessed to have linezolid toxicity. Patients who experienced toxicity displayed a higher baseline creatinine (96.5 µmol/L vs. 79 µmol/L; P = 0.025), lower baseline platelet count (225 × 10 9 /L vs. 278.5 × 10 9 /L; P = 0.002) and received a longer course (median 21 vs. 14 days; P < 0.001) than those who did not. Linezolid TDM was performed in 144 patients (23%). Multivariable logistic regression demonstrated that TDM-guided appropriate dose adjustment significantly reduced the odds of linezolid toxicity (aOR = 0.45; 95% CI 0.21-0.96; P = 0.038) and a treatment duration > 28 days was no longer significantly associated with toxicity., Conclusions: This study confirmed that linezolid treatment-limiting toxicity remains a problem and suggests that TDM-guided dose optimisation may reduce the risk of toxicity and facilitate prolonged courses beyond 28 days., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

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., (© 2021 Royal Australasian College of Physicians.)

Background: Medication reconciliation is an effective strategy to prevent medication errors upon hospital admission and requires obtaining a patient's best possible mediation history (BPMH). However, obtaining a BPMH is time-consuming and pharmacy students may assist pharmacists in this task., Aim: To evaluate the proportion of patients who have an accurate BPMH from the pharmacy student-obtained BPMH compared to the pharmacist-obtained BPMH., Method: Twelve final-year pharmacy students were trained to obtain BPMHs upon admission at 2 tertiary hospitals and worked in pairs. Each student pair completed one 8-h shift each week for 8 weeks. Students obtained BPMHs for patients taking 5 or more medications. A pharmacist then independently obtained and checked the student BPMH from the same patient for accuracy. Deviations were determined between student-obtained and pharmacist-obtained BMPH. An accurate BPMH was defined as only having no-or-low risk medication deviations., Results: The pharmacy students took BPMHs for 91 patients. Of these, 65 patients (71.4%) had an accurate BPMH. Of the 1170 medications included in patients' BPMH, 1118 (95.6%) were deemed accurate. For the student-obtained BPMHs, they were more likely to be accurate for patients who were older (OR 1.04; 95% CI 1.03-1.06; p < 0.001), had fewer medications (OR 0.85; 95% CI 0.75-0.97; p = 0.02), and if students used two source types (administration and supplier) to obtain the BPMH (OR 1.65; 95% CI 1.09-2.50; p = 0.02)., Conclusion: It is suitable for final-year pharmacy students to be incorporated into the BPMHs process and for their BPMHs to be verified for accuracy by a pharmacist., (© 2022. Crown.)

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., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: To assess the agreement in 24-hour area under the curve (AUC 24 ) value estimates between commonly used vancomycin population pharmacokinetic models in the critically ill., Materials and Methods: Adults admitted to intensive care who received intravenous vancomycin and had a serum vancomycin concentration available were included. AUC 24 values were determined using Tucuxi (revision cd7bd7a8) for dosing intervals with a vancomycin concentration using three models (Goti 2018, Colin 2019, and Thomson 2009) previously evaluated in the critically ill. AUC 24 values were categorized as subtherapeutic (<400 mg·h/L), therapeutic (400-600 mg·h/L), or toxic (>600 mg·h/L), assuming a minimum inhibitory concentration of 1 mg/L. AUC 24 value categorization was compared across the three models and reported as percent agreement., Results: Overall, 466 AUC 24 values were estimated in 188 patients. Overall, 52%, 42%, and 47% of the AUC 24 values were therapeutic for the Goti, Colin, and Thomson models, respectively. The agreement of AUC 24 values between all three models was 48% (223/466), Goti-Colin 59% (193/466), Goti-Thomson 68% (318/466), and Colin-Thomson 67% (314/466)., Conclusion: In critically ill patients, vancomycin AUC 24 values obtained from different pharmacokinetic models are often discordant, potentially contributing to differences in dosing decisions. This highlights the importance of selecting the optimal model., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Asad E. Patanwala et al.)

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).

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

The COVID-19 pandemic has required an unprecedented surge in the pharmacy workforce to support mass vaccination hubs. This review discusses the challenges faced while training and credentialing a surge pharmacy workforce and how these challenges were overcome. The process used for training and credentialing new employees has been described and recommendations and insights have been provided based on the lessons learned at two COVID-19 mass vaccination hubs in New South Wales. Operationalising one of the largest mass vaccination hubs in Australia required efficient training and credentialing of the pharmacy workforce. This process included the use of pharmacist-extenders such as students, assistants, and those from other healthcare and non-healthcare backgrounds. Training was optimised by using a flipped classroom model, so that the vaccine preparation process was provided via asynchronous online videos. The videos covered each step of vaccine dose preparation with visual cues to guide appropriate technique. On-site training involved use of simulation and checklists for credentialing. Many factors contributed to the success of this process, including the use of triaging and the re-allocation of personnel based on skill level, collaboration with the Sydney Pharmacy School to train and support a surge workforce involving students, initial on-site information technology support in the form of pharmacy superusers, the use of checklists and guides for troubleshooting, and assigned pharmacy educators to train new employees. The public health response to the COVID-19 pandemic forced us to rapidly adapt to build a pharmacy workforce in record time to support mass vaccination hubs. The recommendations and insights provided from our experience can guide future surges. Some of these concepts may also be applied to pharmacy practice in hospitals when resources are constrained., Competing Interests: None., (© 2022 The Authors. Journal of Pharmacy Practice and Research published by John Wiley & Sons Australia, Ltd on behalf of Society of Hospital Pharmacists of Australia.)

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., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Adverse drug events (ADEs) remain a key contributor to hospitalisations, resulting in long hospital stays and readmissions. Information pertaining to the specific medications and clinical factors associated with these outcomes is limited. Hence, a better understanding of these factors and their relationship to ADEs is required., Objectives: To investigate medications involved, clinical manifestations of ADE-related hospitalisations, and their association with length of stay and readmission., Methods: A retrospective medical record review of patients admitted to a major, tertiary referral hospital in NSW, Australia, from January 2019 to August 2020 was conducted. ADEs were identified using Australian Refined Diagnosis Related Group (AR-DRG) codes: X40, X61, X62 and X64. Medications were classified per the Anatomical Therapeutic Chemical (ATC) classification system and clinical symptoms were classified per the International Classification of Disease (ICD) 9-CM. Logistic regression was performed to assess the relationship between medication and presentation classes with length of stay (≥2 days vs <2 days) and readmission., Results: There were 125 patients who met inclusion criteria (median age = 64 [interquartile range, 45-75] years; 53.6% male). Anti-thrombotic agents, opioids, antidepressants, antipsychotics, insulins and NSAIDs were the most implicated pharmacological classes. Neurological medications and falls were associated with a length of stay ≥2 days (adjusted odds ratio [aOR] 3.92, 95% confidence interval [CI] 1.48-10.33 and aOR 3.24, 95% CI 1.05-10.06, respectively). Neurological medications and neurological and cognitive disorders were associated with an increased likelihood of 90-day readmission (aOR 2.63, 95% CI 1.05-6.57 and aOR 3.20, 95% CI 1.17-8.75, respectively)., Conclusion: This study identified neurological medications as high-risk for increased length of stay and readmission in those hospitalised due to ADEs. This highlights the need for judicious prescribing and monitoring of these medications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Transdermal buprenorphine (TBUP) may be useful for postoperative pain after major surgery, when pain is expected to be severe and sustained. The objective of this study was to compare pain control and opioid consumption in critically ill postoperative patients who were treated with TBUP or not during ICU admission., Design: This was a retrospective, parallel, cohort study., Setting: ICU of a quaternary, urban hospital in Sydney, Australia., Patients: Data were obtained for all patients admitted to the ICU from January 2019 to July 2021 after major gastrointestinal (GI) or genitourinary (GU) surgery., Interventions: TBUP or non-TBUP., Measurements and Main Results: Pain control was compared between patients who received TBUP and those who did not receive TBUP. 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. Inverse probability of treatment weighting was used to adjust for baseline differences. The cohort included 376 patients, with 224 (60%) in the control group and 152 (40%) in the TBUP group. The mean age was 60 ± 14 years, 202 (54%) were male, mean Acute Physiology and Chronic Health Evaluation III score was 44 ± 13, and 147 (39%) received mechanical ventilation. After adjustment, the median probability of significant pain was 0.25 with control and 0.30 with TBUP (median difference, 0.02; 95% CI, 0.04-0.11; p = 0.44). The median opioid consumption (oral morphine milligram equivalents) per day was 5.7 mg with control and 10.1 mg with TBUP (median difference, 0.4 mg; 95% CI, -0.4 to 3.7 mg; p = 0.31)., Conclusions: In patients who are admitted to the ICU after major GI or GU procedures, the use of TBUP in the ICU was not associated with improved pain control or opioid consumption compared with those who did not receive TBUP., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid-related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients., Methods: Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full-text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included., Results: A total of 16 observational studies were included, with only two studies considered as poor quality. Seven studies focused on severe ORADEs including over-sedation and respiratory depression. Common patient risk factors for severe ORADEs included comorbidities (eg, sleep apnea and renal diseases), concurrent use of sedatives, and prior opioid exposure. Nine studies focused on a combination of general ORADEs and common patient risk factors included advanced age, male gender, comorbidities (eg, chronic obstructive pulmonary disease and neurologic disorders), concurrent use of sedating medications, and prior opioid exposure., Conclusions: Successful identification of patient risk factors for ORADEs summarized by this systematic review could benefit clinicians when deciding on the appropriateness of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors., (© 2022 Pharmacotherapy Publications, Inc.)

A recent review of missing data in pharmacy literature has highlighted that a low proportion of studies reported how missing data was handled. In this paper we discuss the concept of missing data in survey research, how missing data is classified, common techniques to account for missingness and how to report on missing data. The paper provides guidance to mitigate the occurrence of missing data through planning. Considerations include estimating expected missing data, intended vs unintended missing data, survey length, working with electronic surveys, choosing between standard and filtered form questions, forced responses and straight-lining, as well as responses that can generate missingness like "I don't know" and "Not Applicable". We introduce methods for analysing data with missing values, such as deletion, imputation and likelihood methods. The manuscript provides a framework and flow chart for choosing the appropriate analysis method based on how much missing data is observed and the type of missingness. Special circumstances involving missing data have been discussed, such as in studies with repeated or cohort measures, factor analysis or as part of data integration. Finally, a checklist of questions are provided for researchers to guide the reporting of the missing data when conducting future research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To identify the proportion of patients with continued opioid use after total hip or knee arthroplasty., Methods: This systematic review and meta-analysis searched Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts for articles published from January 1, 2009, to May 26, 2021. The search terms (opioid, postoperative, hospital discharge, total hip or knee arthroplasty, and treatment duration) were based on 5 key concepts. We included studies of adults who underwent total hip or knee arthroplasty, with at least 3 months postoperative follow-up., Results: There were 30 studies included. Of these, 17 reported on outcomes of total hip arthroplasty and 19 reported on outcomes of total knee arthroplasty, with some reporting on outcomes of both procedures. In patients having total hip arthroplasty, rates of postoperative opioid use at various time points were as follows: at 3 months, 20% (95% CI, 13%-26%); at 6 months, 17% (95% CI, 12%-21%); at 9 months, 19% (95% CI, 13%-24%); and at 12 months, 16% (95% CI, 15%-16%). In patients who underwent total knee arthroplasty, rates of postoperative opioid use were as follows: at 3 months, 26% (95% CI, 19%-33%); at 6 months, 20% (95% CI, 17%-24%); at 9 months, 23% (95% CI, 17%-28%); and at 12 months, 21% (95% CI, 12%-29%). Opioid naïve patients were less likely to have continued postoperative opioid use than those who were opioid tolerant preoperatively., Conclusion: Over 1 in 5 patients continued opioid use for longer than 3 months after total hip or knee arthroplasty. Clinicians should be aware of this trajectory of opioid consumption after surgery., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2021 British Pharmacological Society.)

Objective: To evaluate the cost-effectiveness of tapentadol immediate-release (IR) versus oxycodone IR for post-operative pain after a major hip surgery., Methods: This study has been conducted using an Australian societal perspective, focusing on adult patients after a major hip surgery. A cost-effectiveness analysis was conducted using a decision-analytic model. The model incorporated drug and other resource costs, the probability of opioid-related adverse events, and quality-adjusted life months (QALM) in each treatment arm. A willingness to pay (WTP) threshold of AU$2500 was used per QALM gained. A probabilistic sensitivity analysis was conducted to examine the uncertainty of the assumptions. The primary outcome was the incremental cost-effectiveness ratio (ICER) of tapentadol IR versus oxycodone IR, expressed as Australian dollars (AU$) per QALM gained., Results: Tapentadol IR dominated oxycodone IR, with a cost savings of AU$201 and an increase in QALM by 0.014. The ICER was -13,946 AU$/QALM (negative value attributed to numerator). In the probabilistic sensitivity analysis, 84.2% of the simulations were in favour of tapentadol IR at the WTP threshold., Conclusions: Tapentadol IR may be more cost-effective than oxycodone IR for the treatment of acute postoperative pain after major hip surgeries.

Objective: There is little literature describing the performance of video laryngoscopes for the intubation of pediatric patients in the emergency department (ED). The purpose of this study is to report our experience with direct laryngoscopy (DL), the C-MAC (CMAC), and the GlideScope (GVL) over a 10-year period in an urban academic pediatric ED., Methods: This was an analysis of pediatric intubations prospectively recorded into a Continuous Quality Improvement database in an academic pediatric ED over a 10-year period. Between July 1, 2007, and June 30, 2017, emergency physicians recorded all consecutive intubations performed in the pediatric ED. The database included patient demographics and detailed information on each intubation such as age of the patient, reason for intubation, device(s) used, method of intubation, difficult airway characteristics, adverse events, number of intubation attempts, and outcome of each attempt. All patients younger than 18 years who underwent intubation by an emergency medicine resident using a DL or videolaryngoscope (CMAC or GVL) were included in the study. The primary outcome measure was first-pass success without adverse events (FPS-AE), which was defined as successful tracheal intubation on a single laryngoscope insertion without the occurrence of any adverse events during the peri-intubation period. A multivariate regression analysis was performed to control for potential confounders and included difficult airway characteristic, operator level of training, method of intubation, and patient age., Results: During the study period, 530 intubations were performed in pediatric patients. Of these, 493 intubations met the inclusion criteria and were analyzed (218 DL, 187 CMAC, 88 GVL). The FPS-AE with each device is as follows: DL, 54.1% (n = 118/218); CMAC, 64.0% (n = 119/187); and GVL, 52.3% (n = 46/88). In the logistic regression analysis, compared with DL, the CMAC was associated with a higher FPS-AE (odds ratio, 1.6 [95% confidence interval, 1.03-2.45]), whereas the GVL was not associated with an increased FPS-AE (odds ratio, 0.62 [95% confidence interval, 0.35-1.10])., Conclusions: In this study of pediatric patients intubated in the ED, compared with DL, the CMAC was associated with an increased FPS-AE, but the GVL was not., Competing Interests: Disclosures: Dr Sakles serves as an advisor to Verathon Medical. The other authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background The changing of opioids during the transition of care from hospital to home may be associated with harm. Objective To compare patients receiving tapentadol IR versus oxycodone IR following orthopaedic surgery during hospitalisation with regard to the changing of opioids at hospital discharge. Setting A major metropolitan tertiary referral hospital in Australia. Methods This is a retrospective cohort study. Participants included adult orthopaedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalisation between 1 January 2018 and 30 June 2019. Main outcome measure The proportion of patients for whom the opioid prescribed was changed at hospital discharge. Results The study cohort included 199 patients. Of these, 100 patients received oxycodone and 99 patients received tapentadol post-operatively during hospitalisation. The mean age was 66 years (SD, 12 years) and 111 (56%) were female. The most common surgeries were total knee arthroplasty (91, 46%), total hip arthroplasty (63, 32%) and shoulder surgery (26, 13%). Patients in the tapentadol group were more likely to be changed to a different opioid upon hospital discharge than the oxycodone group (57% versus 9%, difference 48% [95% CI 36-59%, p < 0.01). After adjusting for confounders, post-operative tapentadol use was more likely to be associated with opioid changing upon discharge (OR 16.5, 95% CI 6.7 to 40.8, p < 0.01). Conclusions The post-operative use of tapentadol IR during hospitalisation was associated with an increased likelihood of opioid changing at hospital discharge. This practice could have patient safety implications., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Metaraminol is increasingly used as a vasopressor in critically ill patients. Nevertheless, there remains limited evidence to support its use in international guidelines for management of shock., Objectives: The aim of the study was to describe the pharmacoepidemiology of metaraminol in critically ill patients with shock., Methods: A retrospective observational study was conducted in an intensive care unit (ICU) in Sydney, Australia. Patients admitted during a 1-year time frame who received metaraminol intravenous infusions for management of shock were included., Results: A total of 152 patients were included. When metaraminol was used, it was the most common first-line vasopressor started for management of shock (97%, n = 147) and was used as monotherapy in 53% (n = 81) of patients. The median duration of metaraminol infusion in the ICU was 7 h (interquartile range [IQR] = 3 to 19), and the median maximum metaraminol infusion rate in the ICU was 4.0 mg/h (IQR = 2.5 to 6.0). Peripheral vasopressor infusions were used in 96% (n = 146/152) of patients for a median duration of 7 h (IQR = 2 to 18). In all these cases, the peripheral vasopressor used was metaraminol (100%, n = 146/146). Patients were commonly switched from metaraminol to noradrenaline infusions after insertion of a central venous catheter (R2 = 0.89). Patients treated with metaraminol monotherapy had a lower Acute Physiology and Chronic Health Evaluation III score (58 vs 68; median difference = -9, 95% confidence interval = -16 to -3; p < 0.01) and a shorter duration of overall vasopressor use in the ICU (12 vs 39 h, median difference = -24 h, 95% confidence interval = -31 to -18; p < 0.01) than those treated with combination vasopressors. No extravasation injury was reported in the study cohort., Conclusions: Metaraminol is often administered as a first-line peripheral vasopressor in the ICU and is used as a single agent in patients with lower severity of shock., Competing Interests: Conflict of interest None declared., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings., Methods: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice., Results: The database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm., Conclusion: Cost-avoidance studies of pharmacists' interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice., Summary: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided., Conclusions: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)