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.

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.

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.

Physician preference items: what factors matter to surgeons? Does the vendor matter?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

HIV incidence among people who inject drugs (PWIDs) in Ukraine: results from a clustered randomised trial.

BACKGROUND: HIV prevalence among people who inject drugs (PWID) in Ukraine is among the highest in the world. In this study, we aimed to assess whether a social network intervention was superior to HIV testing and counselling in affecting HIV incidence among PWID. Although this was not the primary aim of the study, it is associated with reducing drug and sex risk behaviours, which were primary aims. METHODS: In this clustered randomised trial, PWID who were 16 years of age or older, had used self-reported drug injection in the past 30 days, were willing to be interviewed for about 1 hour and tested for HIV, were not too impaired to comprehend and provide informed consent, and, for this paper, who tested HIV negative at baseline were recruited from the streets by project outreach workers in three cities in southern and eastern Ukraine: Odessa, Donetsk, and Nikolayev. Index or peer leaders, along with two of their network members, were randomly assigned (1:1) by the study statistician to the testing and counselling block (control group) or the testing and counselling plus a social network intervention block (intervention group). No stratification or minimisation was done. Participants in the network intervention received five sessions to train their network members in risk reduction. Those participants assigned to the control group received no further intervention after counselling. The main outcome of this study was HIV seroconversion in the intent-to-treat population as estimated with Cox regression and incorporating a γ frailty term to account for clustering. This trial is registered with ClinicalTrial.gov, number NCT01159704. FINDINGS: Between July 12, 2010, and Nov 23, 2012, 2304 PWIDs were recruited, 1200 of whom were HIV negative and are included in the present study. 589 index or peer leaders were randomly assigned to the control group and 611 were assigned to the intervention group. Of the 1200 HIV-negative participants, 1085 (90%) were retained at 12 months. In 553·0 person-years in the intervention group, 102 participants had seroconversion (incidence density 18·45 per 100 person-years; 95% CI 14·87-22·03); in 497·1 person-years in the control group 158 participants seroconverted (31·78 per 100 person-years; 26·83-36·74). This corresponded to a reduced hazard in the intervention group (hazard ratio 0·53, 95% CI 0·38-0·76, p=0·0003). No study-related adverse events were reported. INTERPRETATION: These data provide strong support for integrating peer education into comprehensive HIV prevention programmes for PWID and suggest the value in developing and testing peer-led interventions to improve access and adherence to pre-exposure prophylaxis and antiretroviral therapy. FUNDING: The National Institute on Drug Abuse.

Global Forum: An International Perspective on Outpatient Surgical Procedures for Adult Hip and Knee Reconstruction.

Outpatient surgical procedures for adult hip and knee reconstruction are gaining interest on a worldwide basis and have been progressively increasing over the last few years. Preoperative screening needs to concentrate on both the patient's comorbidities and home environment to provide a proper alignment of expectations of the surgeon, the patient, and the patient's family. Preoperative multidisciplinary patient information covering all aspects of the upcoming treatment course is a mandatory step, focusing on pain management and early mobilization. Perioperative pain management includes both multimodal and preventive analgesia. Preemptive medications, minimization of narcotics, and combination of general and regional anesthesia are the techniques required in joint arthroplasty performed as an outpatient surgical procedure. A multimodal blood loss management program should be used with preoperative identification of anemia and attention directed toward minimizing blood loss, considering the use of tranexamic acid during the surgical procedure. Postoperative care extends from the initial recovery from anesthesia to the physical therapist's evaluation of the patient's ambulatory status. After the patient has met the criteria for discharge and has been discharged on the same day of the surgical procedure, a nurse should call the patient later at home to check on wound status, pain control, and muscle weakness, which will be further addressed by physiotherapy and education. Implementing outpatient arthroplasty requires monitoring safety, patient satisfaction, and economic impact.

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.

Public Health Effects of Medical Marijuana Legalization in Colorado.

INTRODUCTION: The public health consequences of the legalization of marijuana, whether for medical or recreational purposes, are little understood. Despite this, numerous states are considering medical or recreational legalization. In the context of abrupt changes in marijuana policy in 2009 in Colorado, the authors sought to investigate corresponding changes in marijuana-related public health indicators. METHODS: This observational, ecologic study used an interrupted time-series analysis to identify changes in public health indicators potentially related to broad policy changes that occurred in 2009. This was records-based research from the state of Colorado and Denver metropolitan area. Data were collected to examine frequency and trends of marijuana-related outcomes in hospital discharges and poison center calls between time periods before and after 2009 and adjusted for population. Analyses were conducted in 2014. RESULTS: Hospital discharges coded as marijuana-dependent increased 1% per month (95% CI=0.8, 1.1, p<0.001) from 2007 to 2013. A change in trend was detected in poison center calls mentioning marijuana (p<0.01). After 2009, poison center calls increased 0.8% per month (95% CI=0.2, 1.4, p<0.01). Poison center calls also increased 56% (95% CI=49%, 63%, p<0.001) in the period following the policy change. Further, there was one hospital discharge coded as dependent for every 3,159 (95% CI=2465, 3853, p<0.001) medical marijuana registrant applications. CONCLUSIONS: The abrupt nature of these changes suggests public health effects related to broad policy changes associated with marijuana. This report may be used to assist in policy decisions regarding the short-term public health effects of marijuana legalization.

Clinical and Administrative Approaches to Improving the Efficiency of Joint Arthroplasty and Reducing Hospital Length of Stay.

In the current health care environment, it is more important than ever for orthopedic surgeons to strive for optimal efficiency and effectiveness. For maximum efficiency, patients can be preselected to limit patient types that commonly require a greater investment of the practice's time and resources. Structuring surgical practices for efficiency may involve rethinking the staffing model, anticipating problems that may occur with individual patients, and enhancing internal and external communications. Turnover time between patients must be measured and minimized, and activity in the operating room--including the surgeon's own technique--must be evaluated and refined where necessary. Clinical advances that can enhance efficiency should be considered. Among such advances are tranexamic acid, intravenous acetaminophen, and bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc). Intravenous acetaminophen and liposomal bupivacaine, in particular, can significantly improve efficiency by reducing the administration of opioid medication during the postoperative period, and thereby reducing opioid-related side effects. Liposomal bupivacaine has also been shown to shorten the hospital length of stay and, in many cases, eliminate the need for costly and inefficient nerve blocks.

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.