Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients-a population pharmacokinetic study.

OBJECTIVES: To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis. METHODS: A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total)  ≥100 mg/L] were simulated for various dosing strategies. RESULTS: Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations >5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by >10-fold during dialysis. CONCLUSIONS: A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.

Early SARS-CoV-2-associated acute transverse myelitis: A case for neurotropism?

There are increasing reports of immune-mediated and para-infectious syndromes beyond the well-known respiratory manifestations of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the spectrum of severe neurological sequelae of SARS-CoV-2 remains undefined. We present the case of a 66-year-old female with rapidly progressive lower limb neurology 3 days post SARS-CoV-2 infection. Clinical and radiological findings were in keeping with transverse myelitis and treatment success was achieved with methylprednisolone and remdesivir. This report will discuss the associations between SARS-CoV-2 and acute transverse myelitis. We believe this is one of few described cases of early SARS-CoV-2-associated transverse myelitis secondary to neurotropism and the first successfully treated with the inclusion of remdesivir in the therapeutic regimen.

Beta-Lactam Antibiotic Therapeutic Drug Monitoring in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.

Patient satisfaction with procedural sedation in the emergency department.

OBJECTIVE: The aim of this study was to determine patient satisfaction with procedural sedation as a function of nature of the procedure and depth of sedation. METHOD: We undertook a prospective observational study of adult patients who received procedural sedation in two EDs (20 month period). The level of sedation was determined by an investigator, using the Observers Assessment of Anaesthesia/Sedation Scale (1 = awake to 6 = no response to noxious stimuli). Patient satisfaction was measured with the Iowa Satisfaction with Anaesthesia Scale after full recovery. This was self-administered, comprised 11 items (e.g. 'I felt pain') and has a score range of -3 (poor satisfaction) to +3 (very satisfied). RESULTS: A total of 163 patients were enrolled (51.2% men, mean age 50.7 years). The median (interquartile range) satisfaction score was 2.7 (0.7). Patient satisfaction was lower among patients who had orthopaedic procedures (median 2.6 vs 2.8, P < 0.01) and among patients who had a pre-sedation opioid (2.6 vs 2.8, P = 0.03). Satisfaction was positively correlated with deeper sedation (Spearman's correlation coefficient 0.49, P < 0.001). Satisfaction also differed significantly between the four most common sedation regimens (P < 0.001). It was greatest among those who were administered propofol with or without fentanyl and least among those who were administered nitrous oxide with or without opioid. Patients sedated with propofol with or without fentanyl had the greatest depths of sedation. There was no difference in satisfaction among patients who were and were not sedated by a consultant (median 2.6 and 2.7, respectively, P = 0.84). CONCLUSION: Generally, the level of patient satisfaction is high. Greater satisfaction is associated with deeper sedation, sedation with propofol and non-orthopaedic procedures.

Observational study of alternative therapies among paediatric emergency department patients.

OBJECTIVE: While complementary medicine use among ED paediatric patients is common, the use of alternative therapies (ATs; physical or spiritual therapies) is unknown. We aimed to determine the 12 month period prevalence and nature of AT use among paediatric patients and parent perceptions of AT use. METHODS: We undertook a cross-sectional survey of a convenience sample of parents of paediatric patients in three EDs in metropolitan Melbourne, Australia (January-June, 2015). Parents were invited to complete a validated, anonymous, self-administered questionnaire. The main outcomes were AT use by the patient and parent perceptions of ATs. RESULTS: A total of 806 parents were enrolled. In the previous 12 months, 393 (48.8%) patients had received at least one AT. There were no gender or ethnicity differences between AT users and non-users. AT use was more common among older patients (P < 0.05). Patients with chronic illness tended to use more ATs (P = 0.12). A total of 1091 courses of 43 different ATs had been provided. The most common were massage (16% of patients), chiropractic therapy (9.8%), relaxation (7.2%), meditation (6.2%) and aromatherapy (6.1%). ATs were generally used for musculoskeletal problems, health maintenance, stress and anxiety. Parents who arranged the ATs were significantly more likely to report that ATs are safe, prevent and treat illness, assist prescription medicines and offer a more holistic approach to healthcare (P < 0.001). CONCLUSION: AT use is common among paediatric ED patients. Parents who arrange AT have differing perceptions of AT usefulness and safety from those who do not.

Usefulness of laboratory and radiological investigations in the management of supraventricular tachycardia.

OBJECTIVE: Although ED patients presenting with supraventricular tachycardia (SVT) are commonly investigated, the value of these investigations has been questioned. We aimed to determine the frequency and utility of investigations in patients with SVT. METHODS: We undertook an explicit retrospective medical record audit of patients with SVT who presented to a single ED (January 2004 to June 2014). Data on demographics, presenting complaints, investigations and outcomes were extracted. The outcomes were nature and utility of investigations. RESULTS: A total of 633 patients were enrolled (mean [SD] age 55.4 [17.7] years, 62% female). Laboratory investigations were common: electrolytes (83.7% of patients), full blood count (81.2%), magnesium (57.5%), calcium (39.3%) and thyroid function (30.3%). These investigations revealed many mildly abnormal results but resulted in electrolyte supplementation in only 19 patients: eight with mild hypokalaemia (potassium 3.0-3.5 mmol/L) and 11 with mild hypomagnesia (magnesium 0.49-1.1 mmol/L). Troponin was ordered for 302 (47.7%) patients, many of whom had no history or risk factors for cardiac disease, or ischaemic symptoms associated with their SVT. The troponin was normal, mildly and moderately elevated in 65.2, 24.5 and 10.2% of cases, respectively. Only seven (1.1%) patients were diagnosed with acute myocardial ischemia. Although 190 (30.0%) patients had a chest X-ray (CXR), it was normal in 78.4% of cases. All CXR abnormalities were incidental and not relevant to the immediate ED management. CONCLUSION: Patients with uncomplicated SVT are over-investigated. Guidelines for ED SVT investigation are recommended. Further research is recommended to determine the indications for each investigation in the setting of SVT.

The effect of provision of pain management advice on patient satisfaction with their pain management: a pilot, randomised, controlled trial (pain advice trial).

OBJECTIVE: We aimed to provide pain advice ('The treatment of pain is very important and be sure to tell the staff when you have pain') as an intervention and evaluate its effect upon patient satisfaction. The purpose of this pilot trial was to ensure the design and methods of a future trial are sound, practicable and feasible. METHOD: We undertook a pilot, randomised, controlled, clinical intervention trial in a single ED. The control arm received standard care. The intervention arm received standard care plus pain advice from an independent investigator. All patients and treating ED staff were blinded to patient enrolment. Patient satisfaction with their pain management (six-point ordinal scale) was measured 48 h post-ED discharge, by a blinded researcher. The primary outcome was satisfaction with pain management. RESULTS: Of the 280 and 275 patients randomised to the control and intervention arms, respectively, 196 and 215 had complete data, respectively. 77.6% (152/196) and 88.8% (191/215) of patients reported being provided with pain advice, respectively (difference 11.3% (95% CI 3.6 to 19.0)). The intervention was associated with absolute and relative increases in patient satisfaction of 6.3% and 14.2%, respectively. 91.3% (179/196) and 76.3% (164/215) of patients who were/were not very satisfied reported having received 'pain advice' (difference 15.0% (95% CI 7.6 to 22.5)). CONCLUSIONS: The intervention to provide pain advice resulted in a non-significant increase in patient satisfaction. A larger multicentre trial is feasible and is recommended to further explore the effects of provision of pain advice. TRIAL REGISTRATION NUMBER: ACTRN12615000097549.