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.

Deficits in preference-based health-related quality of life after complications associated with tibial fracture.

Aims: The aims of this study were to quantify health state utility values (HSUVs) after a tibial fracture, investigate the effect of complications, to determine the trajectory in HSUVs that result in these differences and to quantify the quality-adjusted life years (QALYs) experienced by patients. Patients and Methods: This is an analysis of 2138 tibial fractures enrolled in the Fluid Lavage of Open Wounds (FLOW) and Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) trials. Patients returned for follow-up at two and six weeks and three, six, nine and 12 months. Short-Form Six-Dimension (SF-6D) values were calculated and used to calculate QALYs. Results: Compared with those who did not have a complication, those with a complication treated either nonoperatively or operatively had lower HSUVs at all times after two weeks. The HSUVs improved in all patients with the passage of time. However, they did not return to the remembered baseline preinjury values nor to US age-adjusted normal values by 12 months after the injury. Conclusion: While the acute fracture and complications may have resolved clinically, the detrimental effect on a patient's quality of life persists up to 12 months after the injury. Cite this article: Bone Joint J 2018;100-B:1227-33.

Factors associated with health-related quality of life, hip function, and health utility after operative management of femoral neck fractures.

Aims: The primary aim of this prognostic study was to identify baseline factors associated with physical health-related quality of life (HRQL) in patients after a femoral neck fracture. The secondary aims were to identify baseline factors associated with mental HRQL, hip function, and health utility. Patients and Methods: Patients who were enrolled in the Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH) trial completed the 12-item Short Form Health Survey (SF-12), Western Ontario and McMaster Universities Arthritis Index, and EuroQol 5-Dimension at regular intervals for 24 months. We conducted multilevel mixed models to identify factors potentially associated with HRQL. Results: The following were associated with lower physical HRQL: older age (-1.42 for every ten-year increase, 95% confidence interval (CI) -2.17 to -0.67, p < 0.001); female gender (-1.52, 95% CI -3.00 to -0.05, p = 0.04); higher body mass index (-0.69 for every five-point increase, 95% CI -1.36 to -0.02, p = 0.04); American Society of Anesthesiologists class III ( versus class I) (-3.19, 95% CI -5.73 to -0.66, p = 0.01); and sustaining a displaced fracture (-2.18, 95% CI -3.88 to -0.49, p = 0.01). Additional factors were associated with mental HRQL, hip function, and health utility. Conclusion: We identified several baseline factors associated with lower HRQL, hip function, and utility after a femoral neck fracture. These findings may be used by clinicians to inform treatment and outcomes. Cite this article: Bone Joint J 2018;100-B:361-9.

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.

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.

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.

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.

Comparison of interactive voice response and written self-administered patient surveys for clinical research.

This study compared the use of an interactive voice response (IVR) system with a written survey to collect data. Consecutive patients seen in an orthopedic clinic completed the Short Musculoskeletal Function Assessment (SMFA) by either IVR or written questionnaire and then were asked to complete the form again 3-7 days later using the opposite modality. Patient response rates were analyzed for differences between the self-administered IVR and written modes of administration. Three orthopedic clinics participated in the study. No significant differences between method of administration or individual differences in response per patient were found. Therefore, no significant differences in measurement are found when IVR is compared to the written SMFA.

Determinants of disability after lower extremity fracture.

BACKGROUND: Factors influencing the progression of physical impairment to patient-perceived disability are not well known. We sought to better understand this relationship in the setting of injury. METHODS: We followed a cohort of 302 patients with lower extremity fractures over a 1-year period. Physical impairment was assessed by range of motion, strength, and pain. Range of motion and strength were assessed together as a proportion of normal function of the extremity (impairment score). Pain was assessed using a Visual Analogue Scale (VAS) pain score. Disability was assessed using the Sickness Impact Profile (SIP), a widely used measure of patient-perceived limitations of everyday activities attributable to illness. The SIP was administered during hospitalization to assess preinjury baseline. Impairment assessment and readministration of the SIP were performed at 12 months after injury. RESULTS: Impairment in leg function (range of motion and strength) was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 23% of the variance in overall SIP scores. Likewise, VAS pain score was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 29% of the variance in overall SIP scores. In a multivariate linear regression analysis, variables that were independently associated with overall SIP score included impairment score, VAS pain score, preinjury SIP, poverty status, education status, social support, having hired a lawyer, and involvement with workers' compensation. These variables accounted for 52% of the variance in overall SIP scores at 12 months. CONCLUSION: The degree of physical impairment accounts for only a small amount of the variance in disability from lower extremity fracture. Identifiable patient characteristics including age, socioeconomic status, preinjury health, and social support together with impairment account for over half of the variance in long-term disability. Further research is needed to increase understanding of other factors that influence the progression of impairment to disability, especially those factors that may be amenable to intervention.

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.