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Background The alpha-defensin test has been previously demonstrated to be highly accurate in the diagnosis of prosthetic joint infection (PJI), nearly matching the Musculoskeletal Infection Society definition for PJI. However, the relationship between alpha-defensin levels and differing infecting organism has not yet been investigated. Questions/purposes The purpose of this study is to describe the breadth of organisms that can trigger a positive synovial fluid alpha-defensin test result in the setting of PJI and also to assess the magnitude of the alpha-defensin result in terms of various pathogen characteristics. Methods Between December 2012 and March 2014, one laboratory processed 2319 synovial fluid samples for alpha-defensin testing. The present study reviewed the results of the 1937 samples that simultaneously had a synovial fluid culture performed; these came from 418 surgeons in 42 states. The overall culture-positive rate was 49% (244 of 498) among alpha-defensin-positive synovial fluids and 1% (19 of 1439) among alpha-defensin-negative synovial fluids. The organisms recovered from 244 alpha-defensin-positive, culture-positive fluids were recorded and grouped based on various characteristics, including Gram type, species, virulence, oral pathogenicity, and source joint. Alpha-defensin-negative samples served as uninfected controls. Median alpha-defensin levels were calculated for each group, and Dunn’s multiple comparison test for nonparametric data was used to identify any statistically significant (p < 0.05) organism-specific differences in the alpha-defensin level. Results The alpha-defensin test for PJI was positive in the setting of a wide spectrum of organisms typically causing PJI. The median alpha-defensin level for all 244 alpha-defensin-positive, culture-positive samples (4.7 [interquartile range {IQR}, 3.7–5.3]) was higher than negative controls (0.26 [IQR, 0.22–0.33]) with a median difference of 4.4 (p < 0.001). There were no differences in the median alpha-defensin levels when performing a multiple comparison test among Gram-positive organisms (4.7 [IQR, 3.6–5.3]), Gram-negative organisms (4.8 [IQR, 4.2–5.3]), yeast (4.1 [IQR, 2.2–5.1]), virulent organisms (4.7 [IQR, 3.8–5.2]), less virulent organisms (4.8 [IQR, 3.6–5.4]), oral pathogens (4.5 [IQR, 3.2–5.2]), knees (4.7 [IQR, 3.7–5.3]), hips (4.9 [IQR, 4.1–5.8]), or shoulders (5.3 [IQR, 4.0–10.7]) with all comparisons having a p > 0.999. Conclusions The alpha-defensin test provides consistent results regardless of the organism type, Gram type, species, or virulence of the organism and should be seriously considered to be a standard diagnostic tool in the evaluation for PJI. Future research should focus on the performance of this test in specific clinical scenarios such as the immediate postoperative period in the setting of severe immunocompromise and in the setting of a native joint. Level of Evidence Level III, diagnostic study.

Background Synovial fluid biomarkers have demonstrated diagnostic accuracy surpassing the currently used diagnostic tests for periprosthetic joint infection (PJI). Questions/purposes The purpose of this study is to directly compare the sensitivity and specificity of the synovial fluid α-defensin immunoassay to the leukocyte esterase (LE) colorimetric test strip. Methods Synovial fluid was collected from 46 patients meeting the inclusion criteria of this prospective diagnostic study. Synovial fluid samples were tested with both a novel synovial-fluid-optimized immunoassay for α-defensin and the LE colorimetric test strip. The Musculoskeletal Infection Society (MSIS) definition was used to classify 23 periprosthetic infections and 23 aseptic failures; this classification was used as the standard against which the two diagnostic tests were compared. Results The synovial fluid α-defensin immunoassay correctly predicted the MSIS classification of all patients in the study, demonstrating a sensitivity and specificity of 100% for the diagnosis of PJI. The α-defensin assay could be read for all samples, including those with blood in the synovial fluid. The leukocyte esterase test strip could not be interpreted in eight of 46 samples (17%) as a result of blood interference. Analysis of the LE strips that could be interpreted yielded a sensitivity of 69% and a specificity of 100%. Conclusions The synovial fluid α-defensin immunoassay outperformed the LE colorimetric test strip in this study and provided reliable results even when the LE test strip failed as a result of blood interference. The simple analytic results provided by the α-defensin immunoassay, compared with the more complex and interpretive nature of both the MSIS criteria and LE colorimetric test strip, make it a highly attractive diagnostic tool. Level of Evidence Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Background We have previously described a unique gene expression signature exhibited by synovial fluid leukocytes in response to bacterial infection, identifying a number of potential biomarkers for infection. However, the diagnostic performance of these potential biomarkers in an immunoassay format is unknown. Questions/purposes We therefore evaluated the sensitivity, specificity, and accuracy of several potential synovial fluid biomarkers for infection, and compared them to current standards of testing for periprosthetic infection. Methods We prospectively collected synovial fluid from 14 patients classified as having a periprosthetic infection and 37 patients classified as having an aseptic failure. The synovial fluid samples were tested for 23 potential biomarkers for periprosthetic infection. We then determined differences in biomarker levels between infected and aseptic groups, then computed the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for select biomarkers, and finally compared those to current standard tests for infection. Results Twelve synovial fluid biomarkers had substantially higher average levels in the synovial fluid of infected versus aseptic patients. Synovial fluid levels of IL-1 were a mean of 258 times higher in patients with a periprosthetic infection compared to patients having revision for aseptic diagnoses. Synovial fluid IL-1 and IL-6 levels correctly classified all patients in this study with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy equal to 1. Several markers tested in this study outperformed the ESR and CRP tests. Conclusions Patients with a periprosthetic infection have elevated levels of numerous synovial fluid biomarkers, when compared to patients with aseptic diagnoses. Several of these biomarkers exhibited nearly ideal sensitivity, specificity, and accuracy in this study, suggesting that synovial fluid biomarkers could be a valuable tool for diagnosing periprosthetic infection. Level of Evidence Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Objectives. We investigated whether there were gender differences in chronic medical, psychiatric, and substance-dependence disorders among jail inmates and whether substance dependence mediated any gender differences found. Methods. We analyzed data from a nationally representative survey of 6982 US jail inmates. Weighted estimates of disease prevalence were calculated by gender for chronic medical disorders (cancer, hypertension, diabetes, arthritis, asthma, hepatitis, and cirrhosis), psychiatric disorders (depressive, bipolar, psychotic, posttraumatic stress, anxiety, and personality), and substance-dependence disorders. We conducted logistic regression to examine the relationship between gender and these disorders. Results. Compared with men, women had a significantly higher prevalence of all medical and psychiatric conditions (P ≤ .01 for each) and drug dependence (P < .001), but women had a lower prevalence of alcohol dependence (P < .001). Gender differences persisted after adjustment for sociodemographic factors and substance dependence. Conclusions. Women in jail had a higher burden of chronic medical disorders, psychiatric disorders, and drug dependence than men, including conditions found more commonly in men in the general population. Thus, there is a need for targeted attention to the chronic medical, psychiatric, and drug-treatment needs of women at risk for incarceration, both in jail and after release.

Knowledge of causal processes through mediation analysis can help improve the effectiveness and reduce costs of public health programs, like HIV prevention and treatment interventions. Advancements in mediation using the potential outcomes framework provide a method for estimating the causal effect of interventions on outcomes via a mediating variable. The purpose of this paper is to provide practical information about mediation and the potential outcomes framework that can enhance data analysis and causal inference for intervention studies. Causal mediation effects are defined and then estimated using data from an HIV intervention randomized trial among people who inject drugs (PWID) in Ukraine. Results from a potential outcomes mediation analysis show that the intervention had a total causal effect on incident HIV infection such that participants in the experimental group were 36% less likely to become infected during the 12-month study than those in the control arm, but that neither self-efficacy nor network communication mediated this effect. Because neither putative mediator was significant, measurement and confounding issues should be investigated to rule out these mediators. Other putative mediators, such as injection frequency, route of administration, or HIV knowledge can be considered. Future research is underway to examine additional, multiple mediators explaining efficacy of the current intervention and sensitivity to confounding effects.

Background: Vendors of hip and knee implants court orthopedic surgeons to adopt their products. Hospitals, which have to pay for these products, now court the same surgeons to help reduce the number of vendors and contain implant costs. Purposes: This study measures the surgeon's perceived alignment of interests with both vendors and hospitals and gauges surgeons' exposure and receptivity to hospital cost-containment efforts. Methodology/Approach: We surveyed all practicing orthopedists performing 12 or more implant procedures annually in Pennsylvania. The survey identified the surgeon's preferred vendor, tenure with that vendor, use of the vendor during residency training, receipt of financial payments from the vendor, alignment of interests with both vendor and hospital stakeholders, and exposure and receptivity to hospital cost-containment efforts. Findings: Surgeons have long-standing relationships with implant vendors, but only a small proportion receive financial payments. Surgeons align most closely with the vendor's sales representative and least closely with the hospital's purchasing manager. Paradoxically, surgeons support hospital efforts to limit the number of vendors but report that their own choice of vendor is not constrained. The major drivers of surgeons' alignment and stance toward cost containment are their tenure with and receipt of financial payments from the vendor. Practice Implications: Hospitals face a competitive disadvantage in capturing the attention of orthopedists, compared with implant vendors. The vendors' advantage stems from historical, financial, and service benefits offered to surgeons. Hospital executives now seek to offer comparable benefits to surgeons.

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Despite multiple risk factors for mortality among People Who Inject Drugs (PWID), more research is warranted that examines sub-populations within PWID. Mortality data from PWID participating in longitudinal HIV prevention research in Denver were obtained from The Colorado Department of Public Health and Environment. Risk factors for both all-cause and acute-toxicity related mortality were analyzed using Cox proportional hazards regression. Two-thousand seven individuals were interviewed at baseline. Eighty-six individuals died during the time frame of the study, 58 of which were due to acute-toxicity. Disabled (HR = 3.3, p < 0.001), gay/lesbian-identified (HR = 2.6, p = 0.03), white race/ethnicity (HR = 2.4, p = 0.003), and use of a shared cooker (HR = 2.1, p = 0.01) were important adjusted risk factors. These suggest that drug and HIV interventions should utilize techniques that can address the needs of marginalized populations in addition to HIV drug risk behaviors.

The USA devotes roughly $200 billion (6%) of annual national health expenditures to medical devices. A substantial proportion of this spending occurs during orthopedic (eg, hip and knee) arthroplasties - two high-volume hospital procedures. The implants used in these procedures are commonly known as physician preference items (PPIs), reflecting the physician's choice of implant and vendor used. The foundations for this preference are not entirely clear. This study examines what implant and vendor characteristics, as evaluated by orthopedic surgeons, are associated with their preference. It also examines other factors (eg, financial relationships and vendor tenure) that may contribute to implant preference. We surveyed all practicing orthopedic surgeons performing 12 or more implant procedures annually in the Commonwealth of Pennsylvania. The survey identified each surgeon's preferred hip/knee vendor as well as the factors that surgeons state they use in selecting that primary vendor. We compared the surgeons' evaluation of multiple characteristics of implants and vendors using analysis of variance techniques, controlling for surgeon characteristics, hospital characteristics, and surgeon-vendor ties that might influence these evaluations. Physician's preference is heavily influenced by technology/implant factors and sales/service factors. Other considerations such as vendor reputation, financial relationships with the vendor, and implant cost seem less important. These findings hold regardless of implant type (hip vs knee) and specific vendor. Our results suggest that there is a great deal of consistency in the factors that surgeons state they use to evaluate PPIs such as hip and knee implants. The findings offer an empirically derived definition of PPIs that is consistent with the product and nonproduct strategies pursued by medical device companies. PPIs are products that surgeons rate favorably on the twin dimensions of technology and sales/service.