Prioritizing Research Informing Antibiotic Prophylaxis Guidelines for Knee Arthroplasty Patients.

INTRODUCTION: Guidelines for routine antibiotic prophylaxis (AP) before dental procedures to prevent periprosthetic joint infection (PJI) have been hampered by the lack of prospective clinical trials. OBJECTIVES: To apply value-of-information (VOI) analysis to quantify the value of conducting further clinical research to reduce decision uncertainty regarding the cost-effectiveness of AP strategies for dental patients undergoing total knee arthroplasty (TKA). METHODS: An updated decision model and probabilistic sensitivity analysis (PSA) evaluated the cost-effectiveness of AP and decision uncertainty for 3 AP strategies: no AP, 2-y AP, and lifetime AP. VOI analyses estimated the value and cost of conducting a randomized controlled trial (RCT) or observational study. We used a linear regression meta-modeling approach to calculate the population expected value of partial perfect information and a Gaussian approximation to calculate population expected value of sample information, and we subtracted the cost for research to obtain the expected net benefit of sampling (ENBS). We determined the optimal trial sample sizes that maximized ENBS. RESULTS: Using a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the PSA found that a no-AP strategy had the highest expected net benefit, with a 60% probability of being cost-effective, and 2-y AP had a 37% probability. The optimal sample size for an RCT to determine AP efficacy and dental-related PJI risk would require approximately 421 patients per arm with an estimated cost of $14.7 million. The optimal sample size for an observational study to inform quality-of-life parameters would require 2,211 patients with an estimated cost of $1.2 million. The 2 trial designs had an ENBS of approximately $25 to $26 million. CONCLUSION: Given the uncertainties associated with AP guidelines for dental patients after TKA, we conclude there is value in conducting further research to inform the risk of PJI, effectiveness of AP, and quality-of-life values. KNOWLEDGE TRANSFER STATEMENT: The results of this value-of-information analysis demonstrate that there is substantial uncertainty around clinical, health status, and economic parameters that may influence the antibiotic prophylaxis guidance for dental patients with total knee arthroplasty. The analysis supports the contention that conducting additional clinical research to reduce decision uncertainty is worth pursuing and will inform the antibiotic prophylaxis debate for clinicians and dental patients with prosthetic joints.

Is Antibiotic Prophylaxis Cost-effective for Dental Patients Following Total Knee Arthroplasty?

INTRODUCTION: Routine antibiotic prophylaxis (AP) to prevent prosthetic joint infection remains controversial. The lack of prophylaxis guideline consensus from the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) contributes to clinician confusion. OBJECTIVES: This cost-effectiveness decision model informs the AP debate and guideline development by comparing the benefits, harms, and costs of alternative prophylaxis strategies. METHODS: A Markov state-transition model was developed comparing lifetime health outcomes and costs of alternative AP strategies for dental patients aged 65 y with a history of total knee arthroplasty (TKA). Based on our interpretation of AP recommendations from the AAOS and ADA, incremental cost-effectiveness ratios were calculated to compare the following strategies: no AP, AP for the first 2 y after a TKA, and lifetime AP. RESULTS: The no-AP strategy had the lowest average lifetime costs ($17,119) and quality-adjusted life years (11.2151). Compared with a no-prophylaxis strategy, the 2-y AP strategy had incremental costs of $56 and 0.0006 QALYs gained and was cost-effective (incremental cost-effectiveness ratio = $95,100) when a willingness-to-pay threshold of $100,000 per quality-adjusted life year was used. Based on the results of 1-way sensitivity analysis, the no-AP strategy was cost-effective when we modestly increased base case amoxicillin adverse event estimates that were substantially lower than estimates reported in previous models. When plausible combinations of important model parameters were varied, model results suggested that there may be clinical scenarios when AP may be appropriate for some medically at-risk patient populations. CONCLUSION: The results of cost-effectiveness decision modeling generally support questioning routine AP for dental patients with TKA. Sensitivity analyses suggest that prophylaxis may be cost-effective for patient populations with a higher medical risk of infection. This finding is consistent with the recommendations of the 2015 ADA practice guideline and the appropriate use criteria jointly developed by the AAOS and the ADA. KNOWLEDGE TRANSFER STATEMENT: The results of this decision modeling research support the contention that routine AP before invasive dental procedures to prevent prosthetic joint infection may not be cost-effective for patients without medical conditions, potentially conferring a higher infection risk. Model sensitivity analyses suggest that there may be clinical situations when medically at-risk patients benefit from AP.

Implant-related complications in the treatment of unstable intertrochanteric fractures: meta-analysis of dynamic screw-plate versus dynamic screw-intramedullary nail devices.

The choice between dynamic screw-intramedullary nail (DSIN) devices and dynamic screw-plate (DSP) devices for the fixation of unstable trochanteric fractures remains controversial. This study presents a meta-analysis of fixation failures in unstable trochanteric femoral fractures using DSP devices or DSIN devices. Two independent assessors selected randomised controlled trials using a range of electronic databases, as well as reference lists of selected articles. A study quality checklist was used. The occurrence of fixation failure, in particular cut-out, was the primary subject of analysis using descriptive statistics and random-effect meta-analyses. Seventeen trials were identified. Meta-analyses showed no significant difference in the frequency of implant-related complications between the two types of devices. Iatrogenic femoral fractures associated with the use of DSIN devices represent a rare, but persistent, risk. There was a tendency for less frequent cut-out with intramedullary devices compared with DSP devices.

The use of a locking custom contoured blade plate for peri-articular nonunions.

A retrospective chart and radiographic review was performed of 37 operative procedures over 7 years period for peri-articular nonunions. This was a consecutive cohort from a single orthopedic trauma service of a Level 1 center. Nonunions of the tibia and humerus were treated with blade plates fashioned from standard compression plates. Twenty-nine operative sites were treated successfully. The average age was 45.0 years; the average follow-up being 5.3 years. The average number of operations before blade plate was 4.0 (range 1-16). Sixteen blade plates were performed in patients with a diagnosis of clinical infection and all progressed to union and resolution of infection. Seven tissue transfers were used as adjunctive therapy. Five other patients with blade plate surgery had persistent nonunion, of which four united after a second custom contoured blade plate procedure. This study illustrates that surgeon contoured blade plates are an option for peri-articular nonunions even in the presence of infection. This technique resulted in a high union rate and a low complication rate compared to other options.

Cutaneous metal sensitivity in patients with orthopaedic injuries.

BACKGROUND: Manufactures of orthopaedic fracture implants have turned to titanium in a pure form and an alloy during the past ten to fifteen years. Although primarily because of the biomechanical properties of this metal, concern for allergy to nickel and chromium ions in stainless steel was a factor in these decisions. OBJECTIVES: To document the incidence of baseline sensitivity to metal ions and the incidence of conversion to sensitivity to one of three ions in stainless steel in a population of trauma patients at a Level I trauma center. DESIGN: Prospective, consecutive patient series. SETTING: Level I trauma center. PATIENTS: Patients eighteen years of age and older with no history of metallic implants were recruited for this study between October 1995 and July 1997. Four hundred ninety-three patients had a Finn chamber device with chromium, nickel, and cobalt ions, which were read using a photographic scale on day three. Two hundred forty-two of these patients had placement of a second patch, at a mean interval of 187 days (range 45 to 589 days). INTERVENTION: Internal fixation of fracture or osteotomy with metal implant. MAIN OUTCOME MANAGEMENT: Cutaneous reactivity to metal ions. RESULTS: Prevalence of sensitivity to chromium was 0.2 percent, to nickel 1.3 percent, and to cobalt 1.8 percent. Rates for conversion from a negative to positive status were 2.7 percent for chromium, 3.8 percent for nickel, and 3.8 percent for cobalt. Rates for desensitization (i.e., converting from a positive to negative status) were 2.1 percent for nickel and 3.8 percent for cobalt. CONCLUSION: The prevalence of sensitivity to nickel, cobalt, and chromium is apparently low. Similarly, internal fixation devices composed of stainless steel appear to result in an equal incidence of conversion to metal ionic sensitivity and desensitization to metal ions. It is conceivable that cutaneous sensitivity is not representative of deep immune response.

Treatment of open fractures of the shaft of the tibia.

We have systematically reviewed the effect of alternative methods of stabilisation of open tibial fractures on the rates of reoperation, and the secondary outcomes of nonunion, deep and superficial infection, failure of the implant and malunion by the analysis of 799 citations on the subject, identified from computerised databases. Although 68 proved to be potentially eligible, only eight met all criteria for inclusion. Three investigators independently graded the quality of each study and extracted the relevant data. One study (n = 56 patients) suggested that the use of external fixators significantly decreased the requirement for reoperation when compared with fixation with plates. The use of unreamed nails, compared with external fixators (five studies, n = 396 patients), reduced the risk of reoperation, malunion and superficial infection. Comparison of reamed with unreamed nails showed a reduced risk of reoperation (two studies, n = 132) with the reamed technique. An indirect comparison between reamed nails and external fixators also showed a reduced risk of reoperation (two studies) when using nails. We have identified compelling evidence that unreamed nails reduced the incidence of reoperations, superficial infections and malunions, when compared with external fixators. The relative merits of reamed versus unreamed nails in the treatment of open tibial fractures remain uncertain.

A prospective evaluation of the clinical utility of the lower-extremity injury-severity scores.

BACKGROUND: High-energy trauma to the lower extremity presents challenges with regard to reconstruction and rehabilitation. Failed efforts at limb salvage are associated with increased patient mortality and high hospital costs. Lower-extremity injury-severity scoring systems were developed to assist the surgical team with the initial decision to amputate or salvage a limb. The purpose of the present study was to prospectively evaluate the clinical utility of five lower-extremity injury-severity scoring systems. METHODS: Five hundred and fifty-six high-energy lower-extremity injuries were prospectively evaluated with use of five injury-severity scoring systems for lower-extremity trauma designed to assist in the decision-making process for the care of patients with such injuries. Four hundred and seven limbs remained in the salvage pathway six months after the injury. The sensitivity, specificity, and area under the receiver operating characteristic curve were calculated for the Mangled Extremity Severity Score (MESS); the Limb Salvage Index (LSI); the Predictive Salvage Index (PSI); the Nerve Injury, Ischemia, Soft-Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score (NISSSA); and the Hannover Fracture Scale-97 (HFS-97) for ischemic and nonischemic limbs. The scores were analyzed in two ways: including and excluding limbs that required immediate amputation. RESULTS: The analysis did not validate the clinical utility of any of the lower-extremity injury-severity scores. The high specificity of the scores in all of the patient subgroups did confirm that low scores could be used to predict limb-salvage potential. The converse, however, was not true. The low sensitivity of the indices failed to support the validity of the scores as predictors of amputation. CONCLUSIONS: Lower-extremity injury-severity scores at or above the amputation threshold should be cautiously used by a surgeon who must decide the fate of a lower extremity with a high-energy injury.

Characterization of patients with high-energy lower extremity trauma.

PURPOSE: (a) to report the demographic, socioeconomic, behavioral, social, and vocational characteristics of patients enrolled in a study to examine outcomes after high-energy lower extremity trauma (HELET) and to compare them with the general population; (b) to determine whether characteristics of patients undergoing limb salvage versus amputation after HELET are significantly different from each other. DESIGN AND STUDY POPULATION: A prospective study of 601 patients admitted with high-energy lower extremity trauma to eight Level I trauma centers. PROCEDURES: Patients were evaluated during the initial hospitalization. They are being followed up for 24 months postinjury. Study patients are compared with the general population by using census information, population survey data, and published norms. Characteristics of patients undergoing limb salvage versus amputation are also compared. RESULTS: Most patients were male (77 percent), white (72 percent), and between the ages of twenty and forty-five years (71 percent). Seventy percent graduated from high school (compared with 86 percent nationally) (p < 0.05). One fourth lived in households with incomes below the federal poverty line, compared with 16 percent nationally (p < 0.05). The percentage with no health insurance (38 percent) was also higher than in the general population (20 percent) (p < .05). The percentage of heavy drinkers was over two times higher than reported nationally (p < 0.01). Study patients were slightly more neurotic and extroverted and less open to new experiences. When patient characteristics were compared for those undergoing amputation versus limb salvage, no significant differences were found among any of the variables (p > 0.05). CONCLUSION: In conclusion, LEAP patients differ in important ways from the general population. However, the decision to amputate verus reconstruct does not appear to be significantly influenced by patient characteristics.

Pathophysiology of infections after internal fixation of fractures.

Infection complicating internal fixation of fractures is a serious complication that is difficult to treat. Whenever metallic devices are implanted in vivo, successful biointegration requires that host cells colonize the highly reactive implant surface. Bacteria such as staphylococci can also become adherent to metallic or polymeric implants and will compete with host cells for colonization of the implant surface. Once adherent, these bacteria form a biofilm and undergo phenotypic changes that make them resistant to the normal host immune response as well as to antibiotics. Furthermore, metallic implants themselves cause specific deficits in the function of the local immune system that may render the host response to infection inadequate. Any associated soft-tissue injury causes even greater impairment of local immune function. Despite the potentially detrimental impact of internal fixation, fracture stability is of paramount importance in achieving fracture union and in preventing infection. It has been demonstrated in animal models that contaminated fractures without internal fixation develop clinical infection more commonly than similar fractures treated with internal fixation at the time of colonization. Because of the potential for infection whenever internal fixation is utilized, appropriate prophylactic antibiotic coverage for staphylococci and Gram-negative organisms should be provided. Open wounds and severely damaged soft tissues require aggressive management so that a viable soft-tissue envelope is maintained around the implant. Host factors such as smoking and malnourishment should be corrected. Early diagnosis and aggressive treatment of implant-related infection with antibiotics, debridement, and maintenance of stable internal fixation are essential to successful treatment.

Outcome validation of the AO/OTA fracture classification system.

OBJECTIVES: To determine whether a greater severity of injury as documented by the AO/OTA code would correlate with poor scores of impairment, functional performance, and self-reported health status. DESIGN: Prospective, functional outcome. SETTING: Three Level One Trauma Centers. PATIENTS/PARTICIPANTS: Two hundred patients with unilateral and isolated lower extremity fractures. MAIN OUTCOME MEASUREMENTS: Six- and twelve-month SIP, AMA impairment, and functional performance measures of self-selected walking speed, stair climbing, heel raises, rising from a chair, balance work. RESULTS: At six months post injury, overall impairment was significantly (p < 0.05) higher for patients with Type C versus Type B fractures. A significant difference was found among the A, B, C types and the ROM impairment rating at six months (p = 0.004). Using the Scheffe method, the significant difference was determined to be between the B- and C-type fractures. Overall functional performance scores at six months were shown to have significant (p = 0.01) variation using an ANOVA with the significant variation being between the B and C type. At twelve months, the overall functional performance was significant (p = 0.05). CONCLUSION: Patients with C-type fractures had significantly worse functional performance and impairment compared with patients with B-type fractures but were not significantly different from patients with A-type fractures. AO/OTA code may not be a good predictor of six- and twelve-month functional performance and impairment for patients with isolated unilateral lower extremity fractures.

Short musculoskeletal function assessment questionnaire: validity, reliability, and responsiveness.

BACKGROUND: A short questionnaire on functional status was designed for use in community-based outcome studies and in the management of individual patients who have musculoskeletal disease. As most musculoskeletal care is delivered in community practices, short, validated instruments are necessary to perform clinical studies on the effectiveness of treatment in this setting. METHODS: A forty-six-item questionnaire was created as an extension of the work to develop the longer, 101-item Musculoskeletal Function Assessment (MFA) questionnaire. The Short Musculoskeletal Function Assessment (SMFA) questionnaire consists of the dysfunction index, which has thirty-four items for the assessment of patient function, and the bother index, which has twelve items for the assessment of how much patients are bothered by functional problems. The SMFA questionnaire was evaluated for reliability, validity, and responsiveness in a population of 420 patients who had a musculoskeletal disease or injury. RESULTS: The SMFA questionnaire demonstrated excellent internal consistency and stability, with most values greater than 0.90. Content validity for the dysfunction and bother indexes was supported with very little skew (less than 1.00), few ceiling effects (less than 5 percent), and no floor effects. Convergent validity was supported with significant correlations between the SMFA dysfunction and bother indexes and the physicians' ratings of patient function (for example, activities of daily living, recreational and leisure activities, and emotional function [rho > or = 0.40]) and standard clinical measures (for example, grip strength and walking speed [r > or = 0.401). Convergent and discriminant construct validity of the SMFA indexes were demonstrated (p < 0.01) in comparisons with clinical, demographic, Short Form-36 (SF-36), and life-change data. The responsiveness of the SMFA questionnaire to change over time was demonstrated with standardized response means ranging from moderate (0.76) to large (-1.14) for patients who had changes in health status. CONCLUSIONS: The SMFA questionnaire may be used for clinical assessments of the impact of treatment in groups of patients who have musculoskeletal disease or injury. It also may be used in clinical settings to provide reliable and valid assessments of the health status of an individual patient.

Musculoskeletal function assessment: reference values for patient and non-patient samples.

Although researchers and clinicians are encouraged to use health-status questionnaires to evaluate, monitor, and modify care, their use is hindered by the lack of reference values. Without reference values, it is difficult to interpret or evaluate questionnaire scores. In this paper, we present reference values for the Musculoskeletal Function Assessment, a 101-item health-status questionnaire designed and validated for patients with a broad range of musculoskeletal disorders. We describe reference values for two samples: non-patients (n = 123) and patients with isolated extremity injuries (n = 274). For the non-patient sample, descriptive statistics are presented by age and gender, measured at one point in time. For the patient sample, descriptive statistics are provided for seven Orthopaedic Trauma Association/AO diagnostic groups, measured at two points in time. Reference values for changes in the Musculoskeletal Function Assessment total score are described for patients 3 and 9 months and 6 and 12 months after injury. The total scores by post-injury interval, across the diagnostic groups, are significantly better at follow-up than at baseline (p = 0.00). Reference values for changes in total scores are also described in terms of these diagnostic groups across post-injury intervals. Musculoskeletal Function Assessment total scores for Orthopaedic Trauma Association/AO diagnostic groups are significantly better at follow-up than at baseline (p < 0.03). Changes in the total score are also tested for responsiveness with use of standardized response means. Large effects are demonstrated for patients completing the Musculoskeletal Function Assessment at 3 and 9 months (1.03), and small effects are demonstrated for those completing it at 6 and 12 months (0.49). Moderate and large effects are demonstrated for Orthopaedic Trauma Association/AO diagnostic groups across post-injury intervals.