A pilot, masked, randomized controlled trial to evaluate local gentamicin versus saline in open tibial fractures (pGO-Tibia).

Background: Open tibial fractures have a high risk of infection that can lead to severe morbidity. Antibiotics administered locally at the site of the open wound are a potentially effective preventive measure, but there are limited data evaluating aminoglycoside antibiotics. The objective of this study was to assess the feasibility of a clinical trial to test the efficacy of local gentamicin in reducing the risk of fracture-related infection after open tibial fracture. Methods: This study is a single-center, pilot, masked, randomized controlled trial conducted at the Muhimbili Orthopaedic Institute. Participants were randomized intraoperatively after wound closure to receive gentamicin solution or normal saline solution injected at the fracture site. Follow-ups were completed at 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 1 year postoperatively. The primary feasibility outcomes were the rate of enrollment and retention. The primary clinical outcome was the occurrence of fracture-related infection. Results: Of 199 patients screened, 100 eligible patients were successfully enrolled and randomized over 9 months (11.1 patients/month). Complete data were recorded at baseline and follow-up for >95% of cases. The rate of follow-up at 6 weeks, 3 months, 6 months, 9 months, and 1 year were 70%, 68%, 69%, 61%, and 80%, respectively. There was no difference in adverse events or any of the measured primary and secondary outcomes. Conclusion: This pilot study is among the first to evaluate locally administered gentamicin in open tibial fractures. Results indicate a rigorous clinical trial with acceptable rates of enrollment and follow-up to address this topic is possible in this setting.

Assessment of clinical and radiographic outcomes following retrograde versus antegrade nailing of infraisthmic femoral shaft fractures without the use of intraoperative fluoroscopy in Tanzania.

To compare clinical and radiographic outcomes following antegrade versus retrograde intramedullary nailing of infraisthmic femoral shaft fractures. DESIGN: Secondary analysis of prospective cohort study. SETTING: Tertiary hospital in Tanzania. PARTICIPANTS: Adult patients with infraisthmic diaphyseal femur fractures. INTERVENTION: Antegrade or retrograde SIGN intramedullary nail. OUTCOMES: Health-related quality of life (HRQOL), radiographic healing, knee range of motion, pain, and alignment (defined as less than or equal to 5 degrees of angular deformity in both coronal and sagittal planes) assessed at 6, 12, 24, and 52 weeks postoperatively. RESULTS: Of 160 included patients, 141 (88.1%) had 1-year follow-up and were included in analyses: 42 (29.8%) antegrade, 99 (70.2%) retrograde. Antegrade-nailed patients had more loss of coronal alignment (P = .026), but less knee pain at 6 months (P = .017) and increased knee flexion at 6 weeks (P = .021). There were no significant differences in reoperations, HRQOL, hip pain, knee extension, radiographic healing, or sagittal alignment. CONCLUSIONS: Antegrade nailing of infraisthmic femur fractures had higher incidence of alignment loss, but no detectable differences in HRQOL, pain, radiographic healing, or reoperation. Retrograde nailing was associated with increased knee pain and decreased knee range of motion at early time points, but this dissipated by 1 year. To our knowledge, this is the first study to prospectively compare outcomes over 1 year in patients treated with antegrade versus retrograde SIGN intramedullary nailing of infraisthmic femur fractures.Level of Evidence: III.

Intramedullary nailing versus external fixation for open tibia fractures in Tanzania: a cost analysis.

OBJECTIVES: Open tibia fractures pose a clinical and economic burden that is disproportionately borne by low-income countries. A randomized trial conducted by our group showed no difference in infection and nonunion comparing 2 treatments: external fixation (EF) and intramedullary nailing (IMN). Secondary outcomes favored IMN. In the absence of clear clinical superiority, we sought to compare costs between EF and IMN. DESIGN: Secondary cost analysis. SETTING: Single institution in Tanzania. PATIENTS/PARTICIPANTS: Adult patients with acute diaphyseal open tibia fractures who participated in a previous randomized controlled trial. INTERVENTION: SIGN IMN versus monoplanar EF. MAIN OUTCOME MEASUREMENTS: Direct costs of initial surgery and hospitalization and subsequent reoperation: implant, instrumentation, medications, disposable supplies, and personnel costs.Indirect costs from lost productivity of patient and caregiver.Societal (total) costs: sum of direct and indirect costs.All costs were reported in 2018 USD. RESULTS: Two hundred eighteen patients were included (110 IMN, 108 EF). From a payer perspective, costs were $365.83 (95% CI: $332.75-405.76) for IMN compared with $331.25 ($301.01-363.14) for EF, whereas from a societal perspective, costs were $2664.59 ($1711.22-3955.25) for IMN and $2560.81 ($1700.54-3715.09) for EF. The largest drivers of cost were reoperation and lost productivity. Accounting for uncertainty in multiple variables, probabilistic sensitivity analysis demonstrated that EF was less costly than IMN from the societal perspective in only 55% of simulations. CONCLUSIONS: Intramedullary nail fixation compared with external fixation of open tibia fractures in a resource-constrained setting is not associated with increased cost from a societal perspective.

A study protocol for a Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin versus Saline in Open Tibia Fractures (pGO-Tibia) in Dar es Salaam, Tanzania.

BACKGROUND: Open tibia fractures are a major source of disability in low- and middle-income countries (LMICs) due to the high incidence of complications, particularly infection and chronic osteomyelitis. One proposed adjunctive measure to reduce infection is prophylactic local antibiotic delivery, which can achieve much higher concentrations at the surgical site than can safely be achieved with systemic administration. Animal studies and retrospective clinical studies support the use of gentamicin for this purpose, but no high-quality clinical trials have been conducted to date in high- or low-income settings. METHODS: We describe a protocol for a pilot study conducted in Dar es Salaam, Tanzania, to assess the feasibility of a single-center masked randomized controlled trial to compare the efficacy of locally applied gentamicin to placebo for the prevention of fracture-related infection in open tibial shaft fractures. DISCUSSION: The results of this study will inform the design and feasibility of a definitive trial to address the use of local gentamicin in open tibial fractures. If proven effective, local gentamicin would be a low-cost strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, Registration # NCT03559400 ; Registered June 18, 2018.

Intramedullary Nailing Versus External Fixation in the Treatment of Open Tibial Fractures in Tanzania: Results of a Randomized Clinical Trial.

BACKGROUND: Open tibial fractures are common injuries in low and middle-income countries, but there is no consensus regarding treatment with intramedullary nailing versus external fixation. The purpose of the present study was to compare the outcomes of initial treatment with intramedullary nailing or external fixation in adults with open tibial fractures. METHODS: We conducted a randomized clinical trial (RCT) at a tertiary orthopaedic center in Tanzania. Adults with acute diaphyseal open tibial fractures were randomly assigned to statically locked, hand-reamed intramedullary nailing or uniplanar external fixation. The primary outcome was death or reoperation for the treatment of deep infection, nonunion, or malalignment. Secondary outcomes included quality of life as measured with the EuroQol-5 Dimensions (EQ-5D) questionnaire, radiographic alignment, and healing as measured with the modified Radiographic Union Scale for Tibial fractures (mRUST). RESULTS: Of the 240 patients who were enrolled, 221 (92.1%) (including 111 managed with intramedullary nailing and 110 managed with external fixation) completed 1-year follow-up. There were 44 primary outcome events (with rates of 18.0% and 21.9% in the intramedullary nailing and external fixation groups, respectively) (relative risk [RR] = 0.83 [95% confidence interval (CI), 0.49 to 1.41]; p = 0.505). There was no significant difference between the groups in terms of the rate of deep infection. Intramedullary nailing was associated with a lower risk of coronal malalignment (RR = 0.11 [95% CI, 0.01 to 0.85]; p = 0.01) and sagittal malalignment (RR = 0.17 [95% CI, 0.02 to 1.35]; p = 0.065) at 1 year. The EQ-5D index favored intramedullary nailing at 6 weeks (mean difference [MD] = 0.07 [95% CI = 0.03 to 0.11]; p < 0.001), but this difference dissipated by 1 year. Radiographic healing (mRUST) favored intramedullary nailing at 6 weeks (MD = 1.2 [95% CI = 0.4 to 2.0]; p = 0.005), 12 weeks (MD = 1.0 [95% CI = 0.3 to 1.7]; p = 0.005), and 1 year (MD = 0.8 [95% CI = 0.2 to 1.5]; p = 0.013). CONCLUSIONS: To our knowledge, the present study is the first RCT assessing intramedullary nailing versus external fixation for the treatment of open tibial fractures in sub-Saharan Africa. Differences in primary events were not detected, and only coronal alignment significantly favored the use of intramedullary nailing. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Travel barriers, unemployment, and external fixation predict loss to follow-up after surgical management of lower extremity fractures in Dar es Salaam, Tanzania.

OBJECTIVE: Predict loss to follow-up in prospective clinical investigations of lower extremity fracture surgery. DESIGN: Secondary analysis of 2 prospective clinical trials. SETTING: National public orthopaedic and neurologic trauma tertiary referral hospital in Dar es Salaam, Tanzania, a low-income country in sub-Saharan Africa. PATIENTS/PARTICIPANTS: Three hundred twenty-nine femoral shaft and 240 open tibial shaft fracture patients prospectively enrolled in prospective controlled trials of surgical fracture management by external fixation, plating, or intramedullary nailing between June 2015 and March 2017. INTERVENTION: Telephone contact for failure to attend scheduled 1-year clinic visit. MAIN OUTCOME MEASUREMENTS: Ascertainment of primary trial outcome at 1-year from surgery; post-hoc telephone questionnaire for reasons patient did not attend the 1-year clinic visit. RESULTS: One hundred twenty-seven femur fracture (39%) and 68 open tibia fracture (28%) patients did not attend the 1-year clinic visit. Telephone contact significantly improved ascertainment of the primary study outcome by 20% between 6-month and 1-year clinic visits to 82% and 92% respectively at study completion. Multivariable analysis associated unemployment (OR = 2.5 [1.7-3.9], P < .001), treatment with an external fixator (OR = 1.7 [1.0-2.8], P = .033), and each additional 20 km between residence and clinic (OR = 1.03 [1.00-1.06], P = .047] with clinic nonattendance. One hundred eight (55%) nonattending patients completed the telephone questionnaire, reporting travel distance to the hospital (49%), and travel costs to the hospital (46%) as the most prevalent reasons for nonattendance. Sixty-five percent of patients with open tibia fractures cited relocation after surgery as a contributing factor. CONCLUSIONS: Relocation during recovery, travel distance, travel cost, unemployment, and use of an external fixator are associated with loss to clinical follow-up in prospective investigations of femur and open tibia fracture surgery in this population. Telephone contact is an effective means to assess outcome.

Predictors of lower health-related quality of life after operative repair of diaphyseal femur fractures in a low-resource setting.

BACKGROUND: Little data exists on the negative impact of orthopaedic trauma on quality of life (QOL) in low- and middle-income countries (LMICs). The goal of this study is to investigate the factors associated with lower QOL after operative fixation of femoral shaft fractures in adult patients in a low-resource setting. METHODS: This prospective cohort study followed 272 factures in adults undergoing operative fixation for diaphyseal femur fractures at Tanzania. Patient demographics, injury characteristics, treatment modalities, and functional outcomes up to 1-year post-operatively were evaluated for association with 1-year post-operative EQ-5D QOL scores via univariate linear regression analysis. RESULTS: EQ-5D values were significantly lower at 1 year than at baseline (0.941 vs 0.991, p < 0.0005). CONCLUSIONS: Operative fixation of femoral shaft fractures in LMICs results in return to near baseline QOL. Demographic and treatment factors were not significantly associated with EQ-5D. and several markers of recovery were associated with lower 1 year QOL, including pain, knee stiffness, delayed radiographic healing, complications requiring reoperation. Efforts to reduce perioperative complications may help improve post-operative QOL.

Predictors of Reoperation for Adult Femoral Shaft Fractures Managed Operatively in a Sub-Saharan Country.

BACKGROUND: The optimal treatment for femoral shaft fractures in low-resource settings has yet to be established, in part, because of a lack of data supporting operative treatment modalities. We aimed to determine the reoperation rate among femoral fractures managed operatively and to identify risk factors for reoperation at a hospital in a Sub-Saharan country. METHODS: We conducted a prospective clinical study at a single tertiary care center in Tanzania, enrolling all skeletally mature patients with diaphyseal femoral fractures managed operatively from July 2012 to July 2013. Patients were followed at regular intervals for 1 year postoperatively. The primary outcome was a complication requiring reoperation for any reason. Secondary outcomes were scores on the EuroQol (EQ)-5D, radiographic union score for tibial fractures (RUST), and squat-and-smile test. RESULTS: There were a total of 331 femoral fractures (329 patients) enrolled in the study, with a follow-up rate at 1 year of 82.2% (272 of 331). Among the patients with complete follow-up, 4 injuries were managed with plate fixation and 268 were managed with use of an intramedullary nail. The reoperation rate for plate fixation was 25% (1 of 4) compared with 5.2% (14 of 268) for intramedullary nailing (p = 0.204). As found in a multivariate logistic regression, a small nail diameter, a Winquist type-3 fracture pattern, and varus malalignment of proximal fractures were associated with reoperation. The mean EQ-5D score at 1 year was 0.95 for patients who did not require reoperation compared with 0.83 for patients who required reoperation (p = 0.0002). CONCLUSIONS: Intramedullary nailing for femoral shaft fractures was associated with low risk of reoperation and a nearly full return to baseline health-related quality of life at 1 year of follow-up. There are potentially modifiable risk factors for reoperation that can be identified and addressed through education and dissemination of these findings. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.