Assessing Potential Outcomes Mediation in HIV Interventions.

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.

Interventions to Reduce Drug Use Among Methamphetamine Users at Risk for HIV.

PURPOSE OF REVIEW: This paper reports on the results of a study comparing two behavioral treatments for methamphetamine users. The outcome was the effectiveness of the interventions in reducing meth use. The interventions were contingency management (CM) and contingency management plus strengths-based case management (CM/SBCM). RECENT FINDINGS: CM/SBCM was found to be associated with attending more sessions for people who reported being in a couple. Also, participants who earned more money in the first part of the study were more likely to have more clean urinalysis in the second part of the study. Latent class analysis identified a class of participants who were in a couple, without sexual abuse history, and less meth use at baseline. This class tended to have more clean urinalysis in the CM/SBCM intervention. These results indicate that incentive-based interventions with case management may be useful for helping meth users reduce their drug use.

A Hazard Analysis of Risk Factors of Mortality in Individuals Who Inject Drugs in Denver CO.

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.

Krokodile Injectors in Ukraine: Fueling the HIV Epidemic?

This study was designed to assess the characteristics of krokodile injectors, a recent phenomenon in Ukraine, and HIV-related risk factors among people who inject drugs (PWID). In three Ukraine cities, Odessa, Donetsk and Nikolayev, 550 PWID were recruited between December 2012 and October 2013 using modified targeted sampling methods. The sample averaged 31 years of age and they had been injecting for over 12 years. Overall, 39 % tested positive for HIV, including 45 % of krokodile injectors. In the past 30 days, 25 % reported injecting krokodile. Those who injected krokodile injected more frequently (p < 0.001) and they injected more often with others (p = 0.005). Despite knowing their HIV status to be positive, krokodile users did not reduce their injection frequency, indeed, they injected as much as 85 % (p = 0.016) more frequently than those who did not know their HIV status or thought they were negative. This behavior was not seen in non-krokodile using PWID. Although only a small sample of knowledgeable HIV positive krokodile users was available (N = 12), this suggests that krokodile users may disregard their HIV status more so than nonkrokodile users. In spite of widespread knowledge of its harmful physical consequences, a growing number of PWID are turning to injecting krokodile in Ukraine. Given the recency of krokodile use the country, the associated higher frequency of injecting, a propensity to inject more often with others, and what could be a unique level of disregard of HIV among krokodile users, HIV incidence could increase in future years.

The Alpha-defensin Test for Periprosthetic Joint Infection Responds to a Wide Spectrum of Organisms.

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.

The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip.

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.

Law enforcement practices associated with HIV infection among injection drug users in Odessa, Ukraine.

Despite HIV prevention efforts over the past 10 years in Odessa, Ukraine, HIV rates among injection drug users (IDUs) remain high. We explored whether IDUs' experiences with the police and court system in Odessa were associated with HIV serostatus, after controlling for other factors. Qualitative methods, including semi-structured interviews with the police and members of court (N = 19), and focus groups with IDUs (N = 42), were employed to aid in developing a survey instrument for a larger quantitative phase and to assist in interpreting the findings from the quantitative phase, which included 200 participants who were interviewed and tested for HIV. Overall, 55 % tested positive for HIV. Negative experiences with the police were noted by 86 % and included having preloaded syringes taken (66 %), rushed injections due to fear of the police (57 %), police planting drugs (18 %), paying police to avoid arrest (61 %) and threatened by the police to inform on other IDUs (23 %). HIV positive participants were more likely than those who were negative to report these experiences. In a multiple logistic regression, the most significant correlate of HIV infection was rushed injections due to fear of the police. Police actions in Odessa may be contributing to the continued escalation of HIV among IDUs, underscoring the need for structural interventions.

Individual and network interventions with injection drug users in 5 Ukraine cities.

OBJECTIVES: We evaluated the effects of an individual intervention versus a network intervention on HIV-related injection and sexual risk behaviors among street-recruited opiate injection drug users in 5 Ukraine cities. METHODS: Between 2004 and 2006, 722 opiate injection drug users were recruited to participate in interventions that were either individually based or based on a social network model in which peer educators intervened with their network members. Audio computer-assisted self-interview techniques were used to interview participants at baseline and follow-up. RESULTS: Multiple logistic analyses controlling for baseline injection and sexual risks revealed that both peer educators and network members in the network intervention reduced injection-related risk behaviors significantly more than did those in the individually based intervention and that peer educators increased condom use significantly more than did those in the individual intervention. Individual intervention participants, however, showed significantly greater improvements than did network members with respect to reductions in sexual risk behaviors. CONCLUSIONS: Social network interventions may be more effective than individually based interventions in changing injection risk behaviors among both peer educators and network members. The effectiveness of network interventions in changing sexual risk behaviors is less clear, probably owing to network composition and inhibitions regarding discussing sexual risk behaviors.

Reducing HIV-related risk behaviors among injection drug users in residential detoxification.

This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes.

NIDA's Clinical Trials Network: an opportunity for HIV research in community substance abuse treatment programs.

BACKGROUND/OBJECTIVES: HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. RESULTS: While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. CONCLUSION/SIGNIFICANCE: While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.

Gender differences in chronic medical, psychiatric, and substance-dependence disorders among jail inmates.

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 < or = .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.

Synovial fluid biomarkers for periprosthetic infection.

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.

Facilitating outpatient treatment entry following detoxification for injection drug use: a multisite test of three interventions.

A multisite, randomized trial within the National Drug Abuse Treatment Clinical Trials Network (CTN) was conducted to test 3 interventions to enhance treatment initiation following detoxification: (a) a single session, therapeutic alliance intervention (TA) added to usual treatment; (b) a 2-session, counseling and education, HIV/HCV risk reduction intervention (C&E), added to usual treatment; and (c) treatment as usual (TAU) only. Injection drug users (n=632) enrolled in residential detoxification at 8 community treatment programs were randomized to 1 of the 3 study conditions. TA participants reported entering outpatient treatment sooner and in greater numbers than TAU participants. Reported treatment entry for C&E fell between TA and TAU with no significant differences between C&E and the other conditions. There were no differences among the interventions in retention, as measured by weeks of outpatient treatment for all participants who reported treatment entry. Alliance building interventions appear to be effective in facilitating transfer from detoxification to outpatient treatment, but additional treatment engagement interventions may be necessary to improve retention.

Predictors of methamphetamine injection in out-of-treatment IDUs.

From 2004-2006, 439 injection drug users were recruited in Denver, Colorado, to participate in a study of drug use and HCV risk. Over two-thirds were male, more than half were white, and 28% were methamphetamine injectors. The Risk Behavior Assessment, which assesses demographics, drug use, and HIV risk behaviors, was used. Variables were assessed for association with methamphetamine (MA) injection. A logistic regression model was built using forward stepwise method to determine independent associations between variables of interest and MA injection. The study's limitations are noted, and implications are described.

Implant vendors and hospitals: competing influences over product choice by orthopedic surgeons.

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.

Divergent estimates of HIV incidence among people who inject drugs in Ukraine.

BACKGROUND: Divergent estimates of HIV incidence among people who inject drugs (PWID) in Ukraine have been reported in modeling studies, longitudinal cohort studies, and recent infection assays used in cross-sectional surveys. Estimates range from 0.65 to 24.8 infections per 100 person-years with substantial regional variation. In this paper, we study the sources of this discrepancy. METHODS: We compared baseline characteristics of study subjects recruited in the cross-sectional integrated bio-behavioral surveillance surveys (IBBS) in 2011 and 2013, with those from the longitudinal network intervention trial (network RCT) conducted between 2010 - 2013, the study that found a remarkably high incidence of HIV among PWID in Ukraine. The analysis was conducted for two cities: Mykolaiv and Odesa. RESULTS: Significant differences were found in the characteristics of study subjects recruited in the IBBS surveys and the network RCT, in particular in Odesa, where the mismatch in the estimates of HIV incidence is greatest. In Odesa, recent syringe sharing was about three times as prevalent in the network RCT as in the IBBS; 39% of the network RCT and 16-18% of the IBBS participants indicated stimulants rather than opiates as their drug of choice; 97% of respondents in the network RCT and 45% in the IBBS-2013 reported injecting in a group over half of the time; and the average monthly number of injections in the network RCT was about twice that in the IBBS studies. CONCLUSIONS: Differences in study designs and sampling methodologies may be responsible for the substantial differences in HIV incidence estimates among PWID in Ukraine. The potential sources of selection bias differed between the studies and likely resulted in the recruitment of lower risk individuals into the IBBS studies compared to the network RCT. Risk stratification in the population of PWID may have implications for future surveillance and intervention efforts.