Global HIV Incidence Analysis and Implications for Affordability Using Long-Acting Cabotegravir Versus Continuous and Event-Driven Oral Preexposure Prophylaxis.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC. METHODS: A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy. RESULTS: Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923). CONCLUSIONS: High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets.

Proteomic Analyses of Plasma From Patients With Fracture-Related Infection Reveals Systemic Activation of the Complement and Coagulation Cascades.

OBJECTIVES: The objective of this study was to compare plasma proteomes of patients with confirmed fracture-related infections (FRIs) matched to noninfected controls using liquid chromatography-mass spectrometry. DESIGN: This was a prospective case-control study. SETTING: The study was conducted at a single, academic, Level 1 trauma center. PATIENT SELECTION CRITERIA: Patients meeting confirmatory FRI criteria were matched to controls without infection based on fracture region, age, and time after surgery from June 2019 to January 2022. Tandem mass tag liquid chromatography-mass spectrometry analysis of patient plasma samples was performed. OUTCOME MEASURES AND COMPARISONS: Protein abundance ratios in plasma for patients with FRI compared with those for matched controls without infection were calculated. RESULTS: Twenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls. Abundance ratios for more than 1000 proteins were measured in the 54 plasma samples. Seventy-three proteins were found to be increased or decreased in patients with FRI compared with those in matched controls (unadjusted t test P < 0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component analysis to reduce the dimensionality of the large proteomics dataset. A 3-component principal component analysis accounted for 45.7% of the variation in the dataset and had 88.9% specificity for the diagnosis of FRI. STRING protein-protein interaction network analysis of these 3 PCs revealed activation of the complement and coagulation cascades through the Reactome pathway database (false discovery rates <0.05). CONCLUSIONS: Proteomic analyses of plasma from patients with FRI demonstrate systemic activation of the complement and coagulation cascades. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

Reliability of the Modified Radiographic Union Score for Tibia Fractures (mRUST) for Femoral Shaft Fractures.

OBJECTIVES: To evaluate the interobserver and intraobserver reliability of the modified Radiographic Union Score for Tibia Fractures (mRUST) and the effect of rater experience in evaluation of femoral fractures. DESIGN: Retrospective cohort study. SETTING: Single Level 1 trauma center. PATIENTS/PARTICIPANTS: Patients 18-55 years of age with a femur shaft fracture. INTERVENTION: Intramedullary nail fixation. MAIN OUTCOME MEASUREMENT: Interobserver and intraobserver reliability using the intraclass correlation coefficient. RESULTS: The overall interobserver reliability was 0.96. Among fellowship-trained evaluators, the interobserver reliability was 0.94, and it was 0.92 among trainees. The overall intraobserver reliability was 0.98. The intraobserver reliability was 0.97 among fellowship-trained evaluators and 0.96 for trainees. CONCLUSIONS: These results show high interobserver and intraobserver reliability of mRUST in the evaluation of radiographic healing for femur shaft fractures treated with intramedullary nail. This high reliability was further demonstrated throughout different postoperative healing time frames. In addition, mRUST appears to be reliable when used both by trainees and experienced surgeons for the evaluation of femur shaft fractures. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Risk of Postoperative Sciatic Nerve Palsy After Posterior Acetabular Fracture Fixation: Does Patient Position Matter?

OBJECTIVES: To determine whether the prone or lateral position is associated with postoperative sciatic nerve palsy in posterior acetabular fracture fixation. DESIGN: Retrospective cohort study. SETTING: Three Level I trauma centers. PATIENTS: Patients with acetabular fractures treated with a posterior approach (n = 1045). INTERVENTION: Posterior acetabular fixation in the prone or lateral positions. OUTCOME MEASUREMENTS: The primary outcome was the prevalence of postoperative sciatic nerve palsy by position. Secondary outcomes were risk factors for nerve palsy, using multiple regression analysis and propensity scoring. RESULTS: The rate of postoperative sciatic nerve palsy was 9.5% (43/455) in the prone position and 1.5% (9/590) in the lateral position ( P < 0.001). Intraoperative blood loss and surgical duration were significantly higher for patients who developed a postoperative sciatic nerve palsy. Subgroup analysis showed that position did not influence palsy prevalence in posterior wall fractures. For other fracture patterns, propensity score analysis demonstrated a significantly increased odds ratio of palsy in the prone position [aOR 7.14 (2.22-23.00); P = 0.001]. CONCLUSIONS: With the exception of posterior wall fracture patterns, the results of this study suggest that factors associated with increased risk for postoperative sciatic nerve palsy after a posterior approach are fractures treated in the prone position, increased blood loss, and prolonged operative duration. These risks should be considered alongside the other goals (eg, reduction quality) of acetabular fracture surgery when choosing surgical positioning. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.