Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): Randomized clinical trial

Objective: To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures. Design: A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year. Setting: 43 North American academic trauma centers. Participants: Skeletally mature men or women with an open or closed tibial fracture amenable to intramedullary nail fixation. Exclusions comprised pilon fractures, tibial shaft fractures that extended into the joint and required reduction, pathological fractures, bilateral tibial fractures, segmental fractures, spiral fractures \u3e7.5 cm in length, concomitant injuries that were likely to impair function for at least as long as the patient\u27s tibial fracture, and tibial fractures that showed 1 cm gap after surgical fixation. 3105 consecutive patients who underwent intramedullary nailing for tibial fracture were assessed, 599 were eligible and 501 provided informed consent and were enrolled. Interventions: Patients were allocated centrally to self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation. Main outcom e measures: Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union. Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to ≥80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device. Results: SF-36 PCS data were acquired from 481/501 (96%) patients, for whom we had 2303/2886 (80%) observations, and radiographic healing data were acquired from 482/501 (96%) patients, of whom 82 were censored. Results showed no impact on SF-36 PCS scores between LIPUS and control groups (mean difference 0.55, 95% confidence interval -0.75 to 1.84; P=0.41) or for the interaction between time and treatment (P=0.30); minimal important difference is 3-5 points) or in other functional measures. There was also no difference in time to radiographic healing (hazard ratio 1.07, 95% confidence interval 0.86 to 1.34; P=0.55). There were no differences in safety outcomes between treatment groups. Patient compliance was moderate; 73% of patients administered ≥50% of all recommended treatments. Conclusions: Postoperative use of LIPUS after tibial fracture fixation does not accelerate radiographic healing and fails to improve functional recovery. Study registration: ClinicalTrialGov Identifier: NCT00667849

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Does Critical Illness Change Levofloxacin Pharmacokinetics?

Levofloxacin is commonly used in critically ill patients for which existing data suggest nonstandard dosing regimens should be used. The objective of this study was to compare the population pharmacokinetics of levofloxacin in critically ill and in non-critically ill patients. Adult patients with a clinical indication for levofloxacin were eligible for participation in this prospective pharmacokinetic study. Patients were given 500 mg or 750 mg daily by intravenous administration with up to 11 blood samples taken on day 1 or 2 of therapy. Plasma samples were analyzed and population pharmacokinetic analysis was undertaken using Pmetrics. Thirty-five patients (18 critically ill) were included. The mean (standard deviation [SD]) age, weight, and Cockcroft-Gault creatinine clearance for the critically ill and for the non-critically ill patients were 60.3 (16.4) and 72.0 (11.6) years, 78.5 (14.8) and 70.9 (15.8) kg, and 71.9 (65.8) and 68.2 (30.1) ml/min, respectively. A two-compartment linear model best described the data. Increasing creatinine clearance was the only covariate associated with increasing drug clearance. The presence of critical illness did not significantly affect any pharmacokinetic parameter. The mean (SD) parameter estimates were as follows: clearance, 8.66 (3.85) liters/h; volume of the central compartment (Vc), 41.5 (24.5) liters; intercompartmental clearance constants from central to peripheral, 2.58 (3.51) liters/h; and peripheral to central compartments, 0.90 (0.58) liters/h. Monte Carlo dosing simulations demonstrated that achievement of therapeutic exposures was dependent on renal function, pathogen, and MIC. Critical illness appears to have no independent effect on levofloxacin pharmacokinetics that cannot be explained by altered renal function

Training improves interobserver reliability for the diagnosis of scaphoid fracture displacement

Background The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability.Questions/purposes We tested whether training can improve interobserver reliability and sensitivity, specificity, and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans.Methods Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement, using a web-based rating application. Before rating, observers were randomized to a training group (34 observers) and a nontraining group (30 observers). The training group received an online training module before the rating session, and the nontraining group did not. Interobserver reliability for training and nontraining was assessed by Siegel&rsquo;s multirater kappa and the Z-test was used to test for significance.Results There was a small, but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group. Ratings of radiographs and CT scans combined resulted in moderate agreement for both groups. The average sensitivity, specificity, and accuracy of diagnosing displacement of scaphoid fractures were, respectively, 83%, 85%, and 84% for the nontraining group and 87%, 86%, and 87% for the training group. Assuming a 5% prevalence of fracture displacement, the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group. The negative predictive value was 0.99 in both groups.Conclusions Our results suggest training can improve interobserver reliability and sensitivity, specificity and accuracy for the diagnosis of scaphoid fracture displacement, but the improvements are slight. These findings are encouraging for future research regarding interobserver variation and how to reduce it further.<br /

Diagnosis of elbow fracture patterns on radiographs: interobserver reliability and diagnostic accuracy

Item does not contain fulltextBACKGROUND: Studies of traumatic elbow instability suggest that recognition of a pattern in the combination and character of the fractures and joint displacements helps predict soft tissue injury and guide the treatment of traumatic elbow instability, but there is no evidence that patterns can be identified reliably. QUESTIONS/PURPOSES: We therefore determined (1) the interobserver reliability of identifying specific patterns of traumatic elbow instability on radiographs for subgroups of orthopaedic surgeons; and (2) the diagnostic accuracy of radiographic diagnosis. METHODS: Seventy-three orthopaedic surgeons evaluated 53 sets of radiographs and diagnosed one of five common patterns of traumatic elbow instability by using a web-based survey. The interobserver reliability was analyzed using Cohen's multirater kappa. Intraoperative diagnosis was the reference for fracture pattern in calculations of the sensitivity, specificity, accuracy, and positive predictive and negative predictive values of radiographic diagnosis. RESULTS: The overall interobserver reliability for patterns of traumatic elbow instability on radiographs was kappa=0.41. Treatment of greater than five such injuries a year was associated with greater interobserver agreement, but years in practice were not. Diagnostic accuracy ranged from 76% to 93% and was lowest for the terrible triad pattern of injury. CONCLUSIONS: Specific patterns of traumatic elbow instability can be diagnosed with moderate interobserver reliability and reasonable accuracy on radiographs. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. Methods: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. Results: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. Discussion: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal