Julius A. Bishop

Delayed union and nonunions: epidemiology, clinical issues, and financial aspects.

Fracture healing is a critically important clinical event for fracture patients and for clinicians who take care of them. The clinical evaluation of fracture healing is based on both radiographic findings and clinical findings. Risk factors for delayed union and nonunion include patient dependent factors such as advanced age, medical comorbidities, smoking, non-steroidal anti-inflammatory use, various genetic disorders, metabolic disease and nutritional deficiency. Patient independent factors include fracture pattern, location, and displacement, severity of soft tissue injury, degree of bone loss, quality of surgical treatment and presence of infection. Established nonunions can be characterised in terms of biologic capacity, deformity, presence or absence of infection, and host status. Hypertrophic, oligotrophic and atrophic radiographic appearances allow the clinician to make inferences about the degree of fracture stability and the biologic viability of the fracture fragments while developing a treatment plan. Non-unions are difficult to treat and have a high financial impact. Indirect costs, such as productivity losses, are the key driver for the overall costs in fracture and non-union patients. Therefore, all strategies that help to reduce healing time with faster resumption of work and activities not only improve medical outcome for the patient, they also help reduce the financial burden in fracture and non-union patients.

Assessment of compromised fracture healing.

&NA; No standard criteria exist for diagnosing fracture nonunion, and studies suggest that assessment of fracture healing varies among orthopaedic surgeons. This variability can be problematic in both clinical and orthopaedic trauma research settings. An understanding of risk factors for nonunion and of diagnostic tests used to assess fracture healing can facilitate a systematic approach to evaluation and management. Risk factors for nonunion include medical comorbidities, age, and the characteristics of the injury. The method of fracture management also influences healing. Comprehensive evaluation includes an assessment of the patients symptoms, signs, and immune and endocrine status as well as the biologic capacity of the fracture, presence of infection, and quality of reduction and fixation. Diagnostic tests include plain radiography, CT, ultrasonography, fluoroscopy, bone scan, MRI, and several laboratory tests, including assays for bone turnover markers in the peripheral circulation. A systematic approach to evaluating fracture union can help surgeons determine the timing and nature of interventions.

Operative versus Nonoperative Management of Acute Achilles Tendon Rupture Expected-Value Decision Analysis

Background The optimal management strategy for acute Achilles tendon rupture is controversial. Purpose To determine the optimal management by using expected-value decision analysis. Study Design Cross-sectional study. Methods Outcome probabilities were determined from a systematic literature review, and patient-derived utility values were obtained from a visual analog scale questionnaire. A decision tree was constructed, and fold-back analysis was used to determine optimal treatment. Sensitivity analyses were used to determine the effect of varying outcome probabilities and utilities on decision-making. Results Outcome probabilities (expressed as operative; nonoperative) were as follows: well (0.762; 0.846), rerupture (0.022; 0.121), major complication (0.030; 0.025), moderate complication (0.075; 0.003), and mild complication (0.111; 0.005). Outcome utility values were well operative (7.9), well nonoperative (7.0), rerupture (2.6), major complication (1.0), moderate complication (3.5), and mild complication (4.7). Fold-back analysis revealed operative treatment as the optimal management strategy (6.89 versus 6.30). Threshold values were determined for the probability of a moderate complication from operative treatment (0.21) and the utility of rerupture (6.8). Conclusions Operative management was the optimal strategy, given the outcome probabilities and patient utilities we studied. Nonoperative management was favored by increasing rates of operative complications; operative, by decreasing utility of rerupture. We advocate a model of doctor-patient shared decision-making in which both outcome probabilities and patient preferences are considered.

Prophylactic Pinning of the Contralateral Hip After Unilateral Slipped Capital Femoral Epiphysis

BACKGROUND The management of the contralateral hip after unilateral slipped capital femoral epiphysis is controversial. The purpose of this study was to determine, with use of expected-value decision analysis, the optimal management strategy-prophylactic in situ pinning versus observation-for the contralateral hip. METHODS Outcome probabilities were determined from a systematic review of the literature. Utility values were obtained from a questionnaire on patient preferences completed with use of a visual analog scale by twenty-five adolescent male patients without slipped capital femoral epiphysis. A decision tree was constructed, fold-back analysis was performed to determine the optimal treatment, and one and two-way sensitivity analyses were performed to determine the effect on decision-making of varying outcome probabilities and utilities. RESULTS Observation was the optimal management strategy for the contralateral hip given the outcome probabilities and utilities that we studied (the expected value was 9.5 for observation and 9.2 for prophylactic in situ pinning, with a marginal value of 0.3). Increased rates of a late second slip favored prophylactic in situ pinning (the threshold probability was 27%). Risk-taking patients with a high utility for uncomplicated prophylactic in situ pinning favored prophylaxis (the threshold utility was 9.8). CONCLUSIONS The iatrogenic risks of treating a healthy patient or an uninvolved body part rarely outweigh the potential benefits unless the probability of the adverse event is likely and the consequences of the adverse event are very severe. In this decision analysis, the optimal decision was observation. In cases where the probability of contralateral slipped capital femoral epiphysis exceeds 27% or in cases where reliable follow-up is not feasible, pinning of the contralateral hip is favored. For a given individual patient, the optimal strategy depends not only on probabilities of the various outcomes but also on personal preference. Thus, we advocate a model of doctor-patient shared decision-making in which both the outcome probabilities and the patient preferences are considered in order to optimize the decision-making process. LEVEL OF EVIDENCE Economic and decision analysis, Level III-1 (limited alternatives and costs; poor estimates). See Instructions to Authors for a complete description of levels of evidence.

The osteogenic differentiation of human bone marrow MSCs on HUVEC-derived ECM and β-TCP scaffold.

Extracellular matrix (ECM) serves a key role in cell migration, attachment, and cell development. Here we report that ECM derived from human umbilical vein endothelial cells (HUVEC) promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSC). We first produced an HUVEC-derived ECM on a three-dimensional (3D) beta-tricalcium phosphate (β-TCP) scaffold by HUVEC seeding, incubation, and decellularization. The HUVEC-derived ECM was then characterized by SEM, FTIR, XPS, and immunofluorescence staining. The effect of HUVEC-derived ECM-containing β-TCP scaffold on hMSC osteogenic differentiation was subsequently examined. SEM images indicate a dense matrix layer deposited on the surface of struts and pore walls. FTIR and XPS measurements show the presence of new functional groups (amide and hydroxyl groups) and elements (C and N) in the ECM/β-TCP scaffold when compared to the β-TCP scaffold alone. Immunofluorescence images indicate that high levels of fibronectin and collagen IV and low level of laminin were present on the scaffold. ECM-containing β-TCP scaffolds significantly increased alkaline phosphatase (ALP) specific activity and up-regulated expression of osteogenesis-related genes such as runx2, alkaline phosphatase, osteopontin and osteocalcin in hMSC, compared to β-TCP scaffolds alone. This increased effect was due to the activation of MAPK/ERK signaling pathway since disruption of this pathway using an ERK inhibitor PD98059 results in down-regulation of these osteogenic genes. Cell-derived ECM-containing calcium phosphate scaffolds is a promising osteogenic-promoting bone void filler in bone tissue regeneration.

Locking plate fixation for pediatric femur fractures.

Background: The use of locking plates for pediatric femur fractures has not been studied. Locking plate applications for fractures associated with comminution, osteopenia, or minimal bone available for purchase have been well studied in the adult trauma population. Methods: We conducted a retrospective review of children at our institution treated with a locking plate for a femur fracture. We identified 32 patients treated at an average age of 11 years (6-15 years of age). Locking plates were chosen for comminution in 13 patients, nonmalignant pathologic fracture in 9 patients, fracture location in 7 patients, and osteopenia in 3 patients. All patients were treated with a locking plate and followed up until definitive radiologic union. Results: There were no intraoperative complications related to this technology. All patients were healed with near-anatomic alignment with the exception of 1 patient who had valgus malalignment of 12 degrees, which was of no clinical concern and required no intervention. Seven patients had the plates removed with no noted complications. Conclusions: Locking plates are a safe and effective treatment for children and adolescents with femur fractures that may not be amenable to other current means of stabilization. Level of Evidence: Level IV.

Management of radial nerve palsy associated with humeral shaft fracture: a decision analysis model.

PURPOSE When managing radial nerve palsy associated with a humerus fracture, both surgeon and patient must balance the risks and benefits of performing an invasive surgical procedure to address a functional deficit that is likely, but not certain, to recover with nonsurgical management. The purpose of this study was to better understand the determinants of optimal management strategy using expected-value decision analysis. METHODS Probabilities for the occurrences of the potential outcomes after initial observation or early surgery were determined from a systematic review of the literature. Scores for these outcomes were obtained from a questionnaire on patient preferences completed by 82 subjects without a history of humerus fracture and radial nerve palsy and used in the model as a measure of utility. A decision tree was constructed, fold-back analysis was performed to determine optimal treatment, and sensitivity analyses were used to determine the effect on decision making of varying outcome probabilities and utilities. RESULTS Observation was associated with a value of 8.4 and early surgery a value of 6.7 given the outcome probabilities and utilities studied in this model, making observation the optimal management strategy. When parameters were varied in sensitivity analysis, it was noted that when the rate of recovery after initial observation falls below 40% or when the utility value for successful early surgery rises above 9.4, early surgery is the preferred management strategy. CONCLUSIONS Initial observation was the preferred strategy. In clinical settings in which the likelihood of spontaneous recovery of nerve function is low or when an informed patient has a strong preference for surgery, early surgery may optimize outcome. TYPE OF STUDY/LEVEL OF EVIDENCE Economic and Decision Analysis II.

Cost-Effectiveness Analysis of Primary Arthroscopic Stabilization Versus Nonoperative Treatment for First-Time Anterior Glenohumeral Dislocations

PURPOSE The purpose of this study was to compare the cost-effectiveness of initial observation versus surgery for first-time anterior shoulder dislocation. METHODS The clinical scenario of first-time anterior glenohumeral dislocation was simulated using a Markov model (where variables change over time depending on previous states). Nonoperative outcomes include success (no recurrence) and recurrence; surgical outcomes include success, recurrence, and complications of infection or stiffness. Probabilities for outcomes were determined from published literature. Costs were tabulated from Medicare Current Procedural Terminology data, as well as hospital and office billing records. We performed microsimulation and probabilistic sensitivity analysis running 6 models for 1,000 patients over a period of 15 years. The 6 models tested were male versus female patients aged 15 years versus 25 years versus 35 years. RESULTS Primary surgery was less costly and more effective for 15-year-old boys, 15-year-old girls, and 25-year-old men. For the remaining scenarios (25-year-old women and 35-year-old men and women), primary surgery was also more effective but was more costly. However, for these scenarios, primary surgery was still very cost-effective (cost per quality-adjusted life-year, <

Operative versus nonoperative treatment after primary traumatic anterior glenohumeral dislocation: expected-value decision analysis

25,000). After 1 recurrence, surgery was less costly and more effective for all scenarios. CONCLUSIONS Primary arthroscopic stabilization is a clinically effective and cost-effective treatment for first-time anterior shoulder dislocations in the cohorts studied. By use of a willingness-to-pay threshold of

Open Reduction and Internal Fixation Versus Total Elbow Arthroplasty for the Treatment of Geriatric Distal Humerus Fractures: A Systematic Review and Meta-Analysis.

25,000 per quality-adjusted life-year, surgery was more cost-effective than nonoperative treatment for the majority of patients studied in the model. LEVEL OF EVIDENCE Level II, economic and decision analysis.