Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

In-person cognitive behavioural therapy vs. usual care after surgical management of extremity fractures: an unsuccessful feasibility trial.

BACKGROUND: Extremity fractures are common, and most are managed operatively; however, despite successful reduction, up to half of patients report persistent post-surgical pain. Furthermore, psychological factors such as stress, distress, anxiety, depression, catastrophizing, and fear-avoidance behaviors have been associated with the development of chronic pain. The purpose of this pilot study was to examine the feasibility of a randomized controlled trial to determine the effect of in-person cognitive behavioral therapy (CBT) vs. usual care on persistent post-surgical pain among patients with a surgically managed extremity fracture. METHODS: Eligible patients were randomized to either in-person CBT or usual care. We used four criteria to judge the composite measure of feasibility: 1) successful implementation of CBT at each clinical site, 2) 40 patients recruited within 6 months, 3) treatment compliance in a minimum 36 of 40 participants (90%), and 4) 32 of 40 participants (80%) achieving follow-up at one year. The primary clinical outcome was persistent post-surgical pain at one year after surgery. RESULTS: Only two of the four participating sites were able to implement the CBT regimen due to difficulties with identifying certified therapists who had the capacity to accommodate additional patients into their schedule within the required timeframe (i.e., 8 weeks of their fracture). Given the challenges associated with CBT implementation, only one site was able to actively recruit patients. This site screened 86 patients and enrolled 3 patients (3.5%) over a period of three months. Participants were unable to comply with the in-person CBT, with no participants attending an in-person CBT session. Follow-up at one year could not be assessed as the pilot study was stopped early, three months into the study, due to failure to achieve the other three feasibility criteria. CONCLUSION: Our pilot trial failed to demonstrate the feasibility of a trial of in-person CBT versus usual care to prevent persistent pain after surgical repair of traumatic long-bone fractures and re-enforces the importance of establishing feasibility before embarking on definitive trials. Protocol modifications to address the identified barriers include the delivery of our intervention as a therapist-guided, remote CBT program. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT03196258); Registered June 22, 2017, https://clinicaltrials.gov/ct2/show/NCT03196258.

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371. How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

Pragmatic design and inclusion of patient-partner representatives improves participant experience in clinical research.

Objectives: Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation. Methods: At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings. Results: Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment. Conclusions: Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.

Reamed compared with unreamed nailing of tibial shaft fractures: Does the initial method of nail insertion influence outcome in patients requiring reoperations?

BACKGROUND: Patients with a tibial shaft fracture experiencing their first postoperative complication following treatment with intramedullary nails may be at greater risk of subsequent complications than the whole population. We aimed to determine whether the initial method of nail insertion influences outcome in patients with a tibial shaft fracture requiring multiple reoperations. METHODS: Using the Study to Prospectively Evaluate Reamed Intramedullary Nails in Tibial Shaft Fractures trial data, we categorized patients as those not requiring reoperation, those requiring a single reoperation and those requiring multiple reoperations, and we compared them by nail insertion technique (reamed v. unreamed) and fracture type (open v. closed). We then determined the number of patients whose first reoperation was in response to infection, and we compared other clinical outcomes between the reamed and unreamed groups. RESULTS: Among 1226 patients included in this analysis, 175 (14.27%) experienced a single reoperation and 44 patients (3.59%) underwent multiple reoperations. Nail insertion techniques (reamed v. unreamed) did not play a role in the need to perform multiple reoperations. Seventy-five percent of patients requiring multiple reoperations had open tibial shaft fractures. An equal number of these were reamed and unreamed insertions. The majority of patients had their course complicated by infection and almost 50% of patients whose first reoperation was for infection required more than 2 reoperations for management. The rest required multiple procedures for nonunion or bone loss. CONCLUSION: Our findings corroborate those of other studies, in which open fracture type rather than nail insertion technique was found to be the cause of morbidity following intramedullary nailing of tibial fractures. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov, no. NCT00038129.

Is the use of bipolar hemiarthroplasty over monopolar hemiarthroplasty justified? A propensity score-weighted analysis of a multicentre randomized controlled trial.

Aims: Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we sought to determine if a difference in functional outcomes exists between monopolar and bipolar hemiarthroplasty (HA). Methods: This study is a secondary analysis of patients aged 50 years or older with a displaced femoral neck fracture who were enrolled in the HEALTH trial and underwent monopolar and bipolar HA. Scores from the Western Ontario and McMaster University Arthritis Index (WOMAC) and 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and (MCS) were compared between the two HA groups using a propensity score-weighted analysis. Results: Of 746 HAs performed in the HEALTH trial, 404 were bipolar prostheses and 342 were unipolar. After propensity score weighting, adequate balance between the bipolar and unipolar groups was obtained as shown by standardized mean differences less than 0.1 for each covariable. A total of 24 months after HA, the total WOMAC score and its subcomponents showed no statistically significant difference between the unipolar and bipolar groups. Similarly, no statistically significant difference was found in the PCS and MCS scores of the SF-12 questionnaire. In participants aged 70 years and younger, no difference was found in any of the functional outcomes. Conclusion: From the results of this study, the use of bipolar HA over unipolar design does not provide superior functional outcomes at 24 months postoperatively. The theoretical advantage of reduced acetabular wear with bipolar designs does not appear to influence functional outcomes in the first two years postoperatively.

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.

BACKGROUND: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. OBJECTIVE: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. DESIGN: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424). SETTING: 12 clinical sites in Brazil. PARTICIPANTS: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. INTERVENTION: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. MEASUREMENTS: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. RESULTS: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. LIMITATION: Low event rate overall, consistent with contemporary trials in vaccinated populations. CONCLUSION: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care. PRIMARY FUNDING SOURCE: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.

Development of machine-learning algorithms for 90-day and one-year mortality prediction in the elderly with femoral neck fractures based on the HEALTH and FAITH trials.

To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials. This study included 2,388 patients from the HEALTH and FAITH trials, with 90-day and one-year mortality proportions of 3.0% (71/2,388) and 6.4% (153/2,388), respectively. The mean age was 75.9 years (SD 10.8) and 65.9% of patients (1,574/2,388) were female. The algorithms included patient and injury characteristics. Six algorithms were developed, internally validated and evaluated across discrimination (c-statistic; discriminative ability between those with risk of mortality and those without), calibration (observed outcome compared to the predicted probability), and the Brier score (composite of discrimination and calibration). The developed algorithms distinguished between patients at high and low risk for 90-day and one-year mortality. The penalized logistic regression algorithm had the best performance metrics for both 90-day (c-statistic 0.80, calibration slope 0.95, calibration intercept -0.06, and Brier score 0.039) and one-year (c-statistic 0.76, calibration slope 0.86, calibration intercept -0.20, and Brier score 0.074) mortality prediction in the hold-out set. Using high-quality data, the ML-based prediction models accurately predicted 90-day and one-year mortality in patients aged 50 years or older with a FNF. The final models must be externally validated to assess generalizability to other populations, and prospectively evaluated in the process of shared decision-making.

The impact of heterotopic ossification prophylaxis after surgical fixation of acetabular fractures: national treatment patterns and related outcomes.

BACKGROUND: Heterotopic ossification (HO) is a common complication after surgical fixation of acetabular fractures. Numerous strategies have been employed to prevent HO formation, but results are mixed and optimal treatment strategy remains controversial. The purpose of the study was to describe current national heterotopic ossification (HO) prophylaxis patterns among academic trauma centers, determine the association between prophylaxis type and radiographic HO, and identify if heterogeneity in treatment effects exist based on outcome risk strata. METHODS: We used data from a subset of participants enrolled in the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. We included only patients with closed AO-type 62 acetabular fractures that were surgically treated via a posterior (Kocher-Langenbeck), combined anterior and posterior, or extensile exposure. PREPARE Clinical Trial Registration Number: NCT03523962 Patient population This cohort study was nested within the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. The PREPARE trial is a multicenter cluster-randomized crossover trial evaluating the effectiveness of two alcohol-based pre-operative antiseptic skin solutions. All PREPARE trial clinical centers that enrolled at least one patient with a closed AO-type 62 acetabular fracture were invited to participate in the nested study. RESULTS: 277 patients from 20 level 1 and level 2 trauma centers in the U.S. and Canada were included in this study. 32 patients (12%) received indomethacin prophylaxis, 100 patients (36%) received XRT prophylaxis, and 145 patients (52%) received no prophylaxis. Administration of XRT was associated with a 68% reduction in the adjusted odds of overall HO (OR 0.32, 95% CI, 0.14 - 0.69, p = 0.005). The overall severe HO (Brooker classes III or IV) rate was 8% for the entire cohort; XRT reduced the rate of severe HO in high-risk patients only (p=0.03). CONCLUSION: HO prophylaxis patterns after surgical fixation of acetabular fractures have changed dramatically over the last two decades. Most centers included in this study did not administer HO prophylaxis. XRT was associated with a marked reduction in the rate of overall HO and the rate of severe HO in high-risk patients. Randomized trials are needed to fully elucidate the potential benefit of XRT. PREPARE Clinical Trial Registration Number: NCT03523962.

Local administration of vancomycin powder in orthopaedic fracture surgery: current practice and trends.

Objectives: Surgical site infections in orthopaedic trauma are a significant problem with meaningful patient and health care system-level consequences. Direct application of antibiotics to the surgical field has many potential benefits in reducing surgical site infections. However, to date, the data regarding the local administration of antibiotics have been mixed. This study reports on the variability of prophylactic vancomycin powder use in orthopaedic trauma cases across 28 centers. Methods: Intrawound topical antibiotic powder use was prospectively collected within three multicenter fracture fixation trials. Fracture location, Gustilo classification, recruiting center, and surgeon information were collected. Differences in practice patterns across recruiting center and injury characteristics were tested using chi-square statistic and logistic regression. Additional stratified analyses by recruiting center and individual surgeon were performed. Results: A total of 4941 fractures were treated, and vancomycin powder was used in 1547 patients (31%) overall. Local administration of vancomycin powder was more frequent in open fractures 38.8% (738/1901) compared with closed fractures 26.6% (809/3040) (P < 0.001). However, the severity of the open fracture type did not affect the rate at which vancomycin powder was used (P = 0.11). Vancomycin powder use varied substantially across the clinical sites (P < 0.001). At the surgeon level, 75.0% used vancomycin powder in less than one-quarter of their cases. Conclusions: Prophylactic intrawound vancomycin powder remains controversial with varied support throughout the literature. This study demonstrates wide variability in its use across institutions, fracture types, and surgeons. This study highlights the opportunity for increased practice standardization for infection prophylaxis interventions. Level of Evidence: Prognostic-III.

Change in Gustilo-Anderson classification at time of surgery does not increase risk for surgical site infection in patients with open fractures: A secondary analysis of a multicenter, prospective randomized controlled trial.

Introduction: Open fractures represent a major source of morbidity. Surgical site infections (SSIs) after open fractures are associated with a high rate of reoperations and hospitalizations, which are associated with a lower health-related quality of life. Early antibiotic delivery, typically chosen through an assessment of the size and contamination of the wound, has been shown to be an effective technique to reduce the risk of SSI in open fractures. The Gustilo-Anderson classification (GAC) was devised as a grading system of open fractures after a complete operative debridement of the wound had been undertaken but is commonly used preoperatively to help with the choice of initial antibiotics. Incorrect preoperative GAC, leading to less aggressive initial management, may influence the risk of SSI after open fracture. The objectives of this study were to determine (1) how often the GAC changed from the initial to definitive grading, (2) the injury and patient characteristics associated with increases and decreases of the GAC, and (3) whether a change in GAC was associated with an increased risk of SSI. Methods: Using data from the FLOW trial, a large multicenter randomized study, we used descriptive statistics to quantify how frequently the GAC changed from the initial to definitive grading. We used regression models to determine which injury and patient characteristics were associated with increases and decreases in GAC and whether a change in GAC was associated with SSI. Results: Of the 2420 participants included, 305 participants had their preoperative GAC change (12.6%). The factors associated with upgrading the GAC (from preoperative score to the definitive assessment) included fracture sites other than the tibia, bone loss at presentation, width of wound, length of wound, and skin loss at presentation. However, initial misclassification of type III fractures as type II fractures was not associated with an increased risk of SSI (P = 0.14). Conclusions: When treating patients with open fracture wounds, surgeons should consider that 12% of all injuries may initially be misclassified when using the GAC, particularly fractures that have bone loss at presentation or those located in sites different than the tibia. However, even in misclassified fractures, it did not seem to increase the risk of SSI.

Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Outcomes of arthroscopic-assisted lateral tibial plateau fixation: a systematic review.

PURPOSE: The purpose of this study is to evaluate and summarize the current literature on outcomes of arthroscopic-assisted tibial plateau fixation (AATPF) when applied for only lateral tibial plateau fractures. METHODS: A comprehensive search of nine databases was conducted: ClinicalTrials.gov, Cochrane Library via Wiley, Embase and MEDLINE via Ovid, Global Index Medicus, PubMed, Scopus, SPORTDiscus via EBSCO, and Web of Science Core Collection. The study was performed in concordance with PRISMA guidelines. Studies eligible for inclusions included Schatzker I-III lateral tibial plateau fractures with a minimum of 6-month follow-up. Data extraction was performed by two authors independently using a predesigned form. RESULTS: A total of 17 studies, 7 prospective and 10 retrospective, including 565 patients (age 15-82 years old) treated with AATPF were included in this review with follow-up ranging from 6 to 138 months. All 10 studies that used categorical functional outcomes demonstrated excellent/very good or good outcomes in > 90% of patients. When compared to patients managed with the traditional open reduction internal fixation (ORIF), patients treated with AATPF had statistically significantly better range of motion mean difference [5.21° (95% CI - 2.50 to 12.92, p < 0.0001)], lower blood loss [66.19 mL (95% confidence interval (CI) 32.54-99.84 mL, p < 0.0001)], shorter hospital stay [- 1.41 days (95% CI - 3.39 to 0.58 days, p < 0.0001)], better Hospital Special Surgery score [11.31 (95% CI 6.49-16.12, p < 0.0001)], and higher Rasmussen radiographic score [1.26 (95% CI - 0.72 to 3.23, p < 0.0001)]. CONCLUSION: AATPF is a promising treatment of lateral tibial plateau fractures with some advantages over the traditional ORIF. LEVEL OF EVIDENCE: Therapeutic Level III.

What Is the Prevalence of Intimate Partner Violence and Traumatic Brain Injury in Fracture Clinic Patients?

BACKGROUND: Individuals in violent intimate relationships are at a high risk of sustaining both orthopaedic fractures and traumatic brain injury (TBI), and the fracture clinic may be the first place that concurrent intimate partner violence (IPV) and TBI are recognized. Both IPV and TBI can affect all aspects of fracture management, but prevalence of TBI and comorbid TBI and IPV is unknown. QUESTIONS/PURPOSES: (1) What are the previous-year and lifetime prevalence of IPV and TBI in women presenting to an outpatient orthopaedic fracture clinic? (2) What are the conditional probabilities of TBI in the presence of IPV and the reverse, to explore whether screening for one condition could effectively identify patients with the other? (3) Do patients with TBI, IPV, or both have worse neurobehavioral symptoms than patients without TBI and IPV? METHODS: The study was completed in the fracture clinic at a community Level 1 trauma center in Southern Ontario from July 2018 to March 2019 and included patients seen by three orthopaedic surgeons. Inclusion criteria were self-identification as a woman, age 18 years or older, and the ability to complete forms in English without assistance from the person who brought them to the clinic (for participant safety and privacy). We invited 263 women to participate: 22 were ineligible (for example, they were patients of a surgeon who was not on the study protocol), 87 declined before hearing the topic of the study, and data from eight were excluded because the data were incomplete or lost. Complete data were obtained from 146 participants. Participants' mean age was 52 ± 16 years, and the most common diagnosis was upper or lower limb fracture. Prevalence of IPV was calculated as the number of women who answered "sometimes" or "often" to direct questions from the Woman Abuse Screening Tool, which asks about physical, emotional, and sexual abuse in the past year or person's lifetime. The prevalence of TBI was calculated as the number of women who reported at least one head or neck injury that resulted in feeling dazed or confused or in loss of consciousness lasting 30 minutes or less on the Ohio State University Traumatic Brain Injury Identification Method, a standardized procedure for eliciting lifetime history of TBI through a 3- to 5-minute structured interview. Conditional probabilities were calculated using a Bayesian analysis. Neurobehavioral symptoms were characterized using the Neurobehavioral Symptom Inventory, a standard self-report measure of everyday emotional, somatic, and cognitive complaints after TBI, with total scores compared across groups using a one-way ANOVA. RESULTS: Previous-year prevalence of physical IPV was 7% (10 of 146), and lifetime prevalence was 28% (41 of 146). Previous-year prevalence of TBI was 8% (12 of 146), and lifetime prevalence was 49% (72 of 146). The probability of TBI in the presence of IPV was 0.77, and probability of IPV in the presence of TBI was 0.36. Thus, screening for IPV identified proportionately more patients with TBI than screening for TBI, but the reverse was not true. Neurobehavioral Symptom Inventory scores were higher (more symptoms) in patients with TBI only (23 ± 16) than those with fractures only (12 ± 11, mean difference 11 [95% CI 8 to 18]; p < 0.001), in those with IPV only (17 ± 11) versus fractures only (mean difference 5 [95% CI -1 to -11]; p < 0.05), and in those with both TBI and IPV (25 ± 14) than with fractures only (mean difference 13 [95% CI 8 to 18]; p < 0.001) or those with IPV alone (17 ± 11, mean difference 8 [95% CI -1 to 16]; p < 0.05). CONCLUSION: Using a brief screening interview, we identified a high self-reported prevalence of TBI and IPV alone, consistent with previous studies, and a novel finding of high comorbidity of IPV and TBI. Given that the fracture clinic may be the first healthcare contact for women with IPV and TBI, especially mild TBI associated with IPV, we recommend educating frontline staff on how to identify IPV and TBI as well as implementing brief screening and referral and universal design modifications that support effective, efficient, and accurate communication patients with TBI-related cognitive and communication challenges. LEVEL OF EVIDENCE: Level II, prognostic study.

Association of Patient-Level and Hospital-Level Factors With Timely Fracture Care by Race.

Importance: Racial disparities in treatment benchmarks have been documented among older patients with hip fractures. However, these studies were limited to patient-level evaluations. Objective: To assess whether disparities in meeting fracture care time-to-surgery benchmarks exist at the patient level or at the hospital or institutional level using high-quality multicenter prospectively collected data; the study hypothesis was that disparities at the hospital-level reflecting structural health systems issues would be detected. Design, Setting, and Participants: This cohort study was a secondary analysis of prospectively collected data in the PREP-IT (Program of Randomized trials to Evaluate Preoperative antiseptic skin solutions in orthopaedic Trauma) program from 23 sites throughout North America. The PREP-IT trials enrolled patients from 2018 to 2021, and patients were followed for 1-year. All patients with hip and femur fractures enrolled in the PREP-IT program were included in analysis. Data were analyzed April to September 2022. Exposures: Patient-level and hospital-level race, ethnicity, and insurance status. Main Outcomes and Measures: Primary outcome measure was time to surgery based on 24-hour time-to-surgery benchmarks. Multilevel multivariate regression models were used to evaluate the association of race, ethnicity, and insurance status with time to surgery. The reported odds ratios (ORs) were per 10% change in insurance coverage or racial composition at the hospital level. Results: A total of 2565 patients with a mean (SD) age of 64.5 (20.4) years (1129 [44.0%] men; mean [SD] body mass index, 27.3 [14.9]; 83 [3.2%] Asian, 343 [13.4%] Black, 2112 [82.3%] White, 28 [1.1%] other) were included in analysis. Of these patients, 834 (32.5%) were employed and 2367 (92.2%) had insurance; 1015 (39.6%) had sustained a femur fracture, with a mean (SD) injury severity score of 10.4 (5.8). Five hundred ninety-six patients (23.2%) did not meet the 24-hour time-to-operating-room benchmark. After controlling for patient-level characteristics, there was an independent association between missing the 24-hour benchmark and hospital population insurance coverage (OR, 0.94; 95% CI, 0.89-0.98; P = .005) and the interaction term between hospital population insurance coverage and racial composition (OR, 1.03; 95% CI, 1.01-1.05; P = .03). There was no association between patient race and delay beyond 24-hour benchmarks (OR, 0.96; 95% CI, 0.72-1.29; P = .79). Conclusions and Relevance: In this cohort study, patients who sought care from an institution with a greater proportion of patients with racial or ethnic minority status or who were uninsured were more likely to experience delays greater than the 24-hour benchmarks regardless of the individual patient race; institutions that treat a less diverse patient population appeared to be more resilient to the mix of insurance status in their patient population and were more likely to meet time-to-surgery benchmarks, regardless of patient insurance status or population-based insurance mix. While it is unsurprising that increased delays were associated with underfunded institutions, the association between institutional-level racial disparity and surgical delays implies structural health systems bias.

A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan.

BACKGROUND: Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020. METHODS AND DESIGN: The Aqueous-PREP trial is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. Each participating cluster is randomly assigned in a 1:1 ratio to provide 1 of the 2 study interventions on all eligible patients during a study period. The intervention periods are 2 months in length. After completing a 2-month period, the participating cluster crosses over to the alternative intervention. We plan to enroll a minimum of 1540 patients at 14 sites. RESULTS: The primary outcome is surgical site infection guided by the Centers for Disease Control and Prevention's National Healthcare Safety Network reporting criteria (2017). All participants' surgical site infection surveillance period will end 30 days after definitive fracture management surgery for superficial infections and 90 days after definitive fracture management surgery for deep incisional or organ/space infections [1]. The secondary outcome is an unplanned fracture-related reoperation within 12 months of the fracture. CONCLUSION: This manuscript serves as the formal statistical analysis plan (version 1.0) for the Aqueous-PREP trial. The statistical analysis plan was completed on February 28, 2022.