A randomized controlled study of intervention to improve continuity care engagement among HIV-infected persons after release from jails.

Short-term stay, multiple jail admissions and social and financial difficulties are significant obstacles for continuity care engagement (CCE) after release among HIV-infected jail detainees. However, data existing on interventions or strategies to increase post-release CCE among this population are limited. We conducted a randomized controlled study among HIV-infected detainees at Cook County Jail during 2011-2014. The intervention group received telephone contact within 2-4 days of release by a continuity clinic coordinator, who scheduled and informed the ex-detainees of their appointment date within 6 weeks post-release plus standard of care, while the control group received standard of care. The standard of care included comprehensive discharge planning, offering substance abuse treatment and provision of information on how to self-schedule an appointment with the chosen clinics. Of the 166 detainees enrolled, 56 were excluded due to being sent to prison or re-incarcerated within 6 weeks. The final cohort included 55 detainees in each of the groups. The rate of CCE within 6 weeks after release was significantly higher in the intervention group compared to the control group (58% vs. 33%; P = .007). In multivariable logistic regression analysis, being in the control group was the only factor associated with no CCE within 6 weeks (adjusted odds ratio 2.66; 95% confidence interval 1.18-6.00; P = .02). The study findings suggest that the simple telephone contact intervention significantly improved CCE among HIV-infected jail detainees.

Dissemination of Evidence From Systematic Reviews Through Academic CME Providers: A Feasibility Study.

INTRODUCTION: Although systematic reviews represent a source of best evidence to support clinical decision-making, reviews are underutilized by clinicians. Barriers include lack of awareness, familiarity, and access. Efforts to promote utilization have focused on reaching practicing clinicians, leaving unexplored the roles of continuing medical education (CME) directors and faculty in promoting systematic review use. This study explored the feasibility of working with CME directors and faculty for that purpose. METHODS: A convenience sample of five academic CME directors and faculty agreed to participate in a feasibility study exploring use in CME courses of systematic reviews from the Agency for Healthcare Research and Quality (AHRQ-SRs). AHRQ-SR topics addressed the comparative effectiveness of health care options. Participants received access to AHRQ-SR reports, associated summary products, and instructional resources. The feasibility study used mixed methods to assess 1) implementation of courses incorporating SR evidence, 2) identification of facilitators and barriers to integration, and 3) acceptability to CME directors, faculty, and learners. RESULTS: Faculty implemented 14 CME courses of varying formats serving 1700 learners in urban, suburban, and rural settings. Facilitators included credibility, conciseness of messages, and availability of supporting materials; potential barriers included faculty unfamiliarity with SRs, challenges in maintaining review currency, and review scope. SR evidence and summary products proved acceptable to CME directors, course faculty, and learners by multiple measures. DISCUSSION: This study demonstrates the feasibility of approaches to use AHRQ-SRs in CME courses/programming. Further research is needed to demonstrate generalizability to other types of CME providers and other systemic reviews.

Relationship among knowledge acquisition, motivation to change, and self-efficacy in CME participants.

INTRODUCTION: The relationship among an individual's sense of self-efficacy, motivation to change, barriers to change, and the implementation of improvement programs has been reported. This research reports the relationship among self-efficacy, motivation to change, and the acquisition of knowledge in a continuing medical education (CME) activity. METHODS: The measure of individual sense of self-efficacy was a 4-item scale. The measure of motivation was a 6-item scale following on the work of Prochaska and colleagues. The knowledge acquisition was measured in a simple post measure. The participants were enrolled in a CME activity focused on HIV.  RESULTS: The CME activities had a significant effect on knowledge. Preliminary analysis demonstrates a relationship among the self-efficacy measure, the motivation to change measure, and global intent to change. Specifically, as reported earlier, the sense of efficacy in effecting change in the practice environment is predictive of a high level of motivation to change that, in turn, is predictive of formation of intent to change practice patterns. Interestingly, there were also relationships among the self-efficacy measure, the motivation to change measure, and knowledge acquisition. Finally, as expected, there was a significant relationship between knowledge and intent to change practice.  DISCUSSION: Further inspection of the motivation to change construct suggests that it mediates the self-efficacy constructs' effect on intent as well as its effect on knowledge acquisition. This new finding suggests that the proximal construct motivation completely masks an important underlying causal relationship that appears to contribute to practice change as well as learning following CME-self-efficacy.

Relationship among practice change, motivation, and self-efficacy.

INTRODUCTION: The relationship between an individual's sense of self-efficacy, motivation to change, and the implementation of improvement programs has been reported. This research reports the relationship among self-efficacy, motivation to change, and intent to implement continuing medical education (CME) activity learnings. METHODS: The measure of individual sense of self-efficacy was a 4-item scale. The measure of motivation was a 4-item scale following on the work of Johnson, et al. The self-efficacy scale has been confirmed for structure, and together the 2 scales provide indicators of 3 underlying variables-2 self-efficacy constructs and a motivation variable. In addition, a global intent to implement measure was collected. RESULTS: Preliminary analysis demonstrates a significant relationship between a self-efficacy construct, the motivation to change construct, and global intent to change. Specifically, the sense of efficacy in effecting change in the practice environment is predictive of a high level of motivation to change, which, in turn, is predictive of formation of an intent to change practice patterns. DISCUSSION: Further inspection of the motivation to change construct suggests that it mediates the self-efficacy constructs' effect on intent. This is consistent with an earlier report on the relationship among self-efficacy, barriers to change, and stated intent. This new finding suggests that the proximal construct motivation completely masks an important underlying causal relationship that appears to contribute to practice change following CME: self-efficacy. A focus on the participants' sense of self-agency may provide a path to practice change.

Opt-out screening for Chlamydia trachomatis and Neisseria gonorrhoeae in female detainees at Cook County jail in Chicago, IL.

BACKGROUND: In April of 2011, the Cook County Jail initiated opt-out screening of all women for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) at the time of intake. In this retrospective review, we assess the impact of opt-out protocol on rates of testing, diagnoses, and successful treatment. METHODS: We collected the results of all CT and GC tests ordered during intake from April 2011 through December 2012 and reviewed the medical chart of every patient with a positive result for documentation of treatment. Univariable and multivariable analyses were performed to examine the factors associated with receipt of treatment. RESULTS: Opt-out screening increased the number of diagnoses by more than 4-fold (from 9.3 to 40.8 cases/mo). Among 17,065 women eligible for screening, 3729 (22%) women opted out of screening, and screening was completed in 9265 (54.2%). There were 235 (2.5%) gonococcal infections and 702 (7.6%) chlamydial infections. Of 866 women with a positive test result, 602 (69.5%) received treatment while in jail. In multivariable analysis, older age (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.14-2.63), pregnancy (aOR, 2.51; 95% CI, 1.22-5.18), and longer length of stay in jail (aOR, 18.1; 95% CI, 11.7-28.1) were associated with greater likelihood of treatment. CONCLUSIONS: Women entering the Cook County Jail have high prevalence of GC/CT infections. Opt-out screening increased the number of GC and CT diagnoses made, and a high proportion of women were treated while incarcerated. Significant challenges remain in ensuring that screening is completed for all women who do not opt out and in providing treatment to women with short duration of incarceration.

Renal Function Recovery and HIV Viral Suppression Following Tenofovir Discontinuation for Renal Impairment.

BACKGROUND: Tenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN. METHODS: This was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression. RESULTS: Eighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent. CONCLUSION: In this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.

Continuity of care in a cohort of HIV-infected former jail detainees.

This article describes a retrospective cohort study of HIV-infected jail detainees cared for at the Cook County Jail Clinic (CCJC), Illinois, between January and June 2007. Continuity care engagement (CCE) was defined as being seen at least once within 6 months after release at the designated continuity clinics. Being highly active antiretroviral therapy (HAART) naïve during or prior to detention, no prior HIV care, and detectable viral load at initial CCJC visit were associated with continuity care nonengagement (CCNE), while being HAART naïve during detention was the only independent predictor for CCNE. Identification of at-risk detainees and interventions based on these findings should be considered to improve CCE in this population.

Seroprevalence study using oral rapid HIV testing in a large urban emergency department.

BACKGROUND: The Centers for Disease Control (CDC) recommends universal human immunodeficiency virus (HIV) testing for patients aged 13-64 years in health care settings where the seroprevalence is>0.1%. Rapid HIV testing has several advantages; however, recent studies have raised concerns about false positives in populations with low seroprevalence. STUDY OBJECTIVES: To determine the seroprevalence of HIV in our Emergency Department (ED) population, understand patient preferences toward rapid testing in the ED, and evaluate the performance of a rapid oral HIV test. METHODS: A serosurvey offered oral rapid HIV 1/2 testing (OraQuick ADVANCE, Bethlehem, PA) to a convenience sample of 1348 ED patients beginning August 2008. Subjects declining participation were asked to complete an opt-out survey. RESULTS: 1000 patients were tested. Twelve had positive results (1.2%), including one who had newly diagnosed HIV infection; 988 patients tested negative. Of these, 335 (33.3%) had never been tested; 640 had prior history of a negative HIV test. No false-positive rapid HIV results were detected; 98.7% received the results of their preliminary HIV test, including 100% of those who tested positive. Most subjects who declined testing cited either a recent negative HIV test (160/348) or low perceived risk (65/348). A minority cited a concern regarding their privacy (11/348) or that the test might delay their treatment (7/348). CONCLUSIONS: The seroprevalence estimate of 1.2% was above the rate recommended by the CDC for routine universal opt-out testing in our study population. The acceptance rate of rapid HIV testing and the percentage of patients receiving results approximated other recent reports.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.

BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

Classic pyomyositis of the extremities as an unusual manifestation of Blastomyces dermatitidis: a report of two cases.

Pyomyositis is an infection of skeletal muscle that, by definition, arises intramuscularly rather than secondarily from adjacent infection. It is usually associated with bacterial infection, particularly Staphylcococcus aureus. Fungi are rare causes, and Blastomyces dermatitidis has not been reported previously. In this case series, we report two cases of pyomyositis caused by B. dermatitidis. Cases were prospectively identified through routine clinical care at a single academic referral hospital. Two patients with complaints of muscle pain and subacute cough were treated at our hospital in 2007. Both patients were found to have pyomyositis caused by B. dermatitidis- in the quadriceps muscles in one patient, and in the calf muscle in another - by radiological imaging and fungal culture. Both were also diagnosed with pneumonia caused by B. dermatitidis (presumptive in one, confirmed in the other). There was no evidence of infection of adjacent structures, suggesting that the route of infection was likely direct haematogenous seeding of the muscle. A review of the literature confirmed that although B. dermatitidis has been described as causing axial muscle infection secondary to adjacent infection such as vertebral osteomyelitis, our description of isolated muscle involvement (classic pyomyositis) caused by B. dermatitidis, particularly of the extremity muscles, is unique. We conclude that B. dermatitidis is a potential cause of classic pyomyositis.

White matter anisotropy and depression symptoms in patients with HIV.

HIV is associated with increased risk for depression. Normal appearing white matter (NAWM) fractional anisotropy in 15 HIV-seropositive (HIV+) adults with depressive symptoms was compared to 15 HIV+ adults without depressive symptoms. HIV+ adults with depressive symptoms showed increased NAWM fractional anisotropy within the left thalamus, the temporal, and frontal regions, as well as the right cingulate. Discrete components of depression were associated with distinct regional NAWM fractional anisotropy increases. These results demonstrate altered neural complexity in HIV+ adults with depressive symptoms and support the notion that depression is multifactorial with different morphological alterations contributing to discrete aspects of depression.

Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment.

BACKGROUND: We evaluated the immunologic impact of highly active antiretroviral therapy in subjects who maintained human immunodeficiency virus type 1 (HIV-1) suppression through 6 years of receiving a lopinavir-ritonavir-based regimen. METHODS: A total of 100 antiretroviral-naive subjects with any CD4+ T cell count initiated therapy with lopinavir-ritonavir, stavudine, and lamivudine. Sixty-three subjects who remained in the study for 6 years were assessed. Laboratory measurements included plasma HIV-1 RNA levels, multiparameter flow cytometry of immune cells, and markers of maturation and activation. RESULTS: After 6 years, 62 of 63 subjects had plasma HIV-1 RNA levels <50 copies/mL. The mean increase in CD4+ T cell count was 528 cells/microL (P<.001), and 81% of subjects had CD4+ T cell counts >500 cells/microL, compared with 21% of subjects at baseline. The mean ratio of CD4+ T cell count to CD8+ T cell count increased from 0.38 at baseline to 0.96 at year 6 (P<.001). The percentage of subjects with cell counts below the lower limit of normal at year 6, compared with at baseline, was significantly decreased for total T cells, B cells, and natural killer cells. At year 6, the median CD4+ T cell activation level was 3.4%, and the median CD8+ T cell activation level was 5.8%. CONCLUSIONS: The receipt of a lopinavir-ritonavir-based regimen resulted in ongoing immune reconstitution through 6 years of therapy in a cohort of HIV-1-infected, antiretroviral-naive subjects with suppressed HIV-1 RNA levels. Normalization of activation marker expression on CD4+ and CD8+ T cell subsets was demonstrated.

HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study.

OBJECTIVE: There are conflicting reports of adverse HIV-associated alterations in white matter integrity as measured by diffusion tensor imaging (DTI). We sought to address these conflicting reports by assessing, on a voxel-by-voxel basis, HIV-associated regional changes in radiologically defined normal-appearing white matter (NAWM) integrity using high-resolution DTI. METHODS: 30 HIV-seropositive (SP) and 30 HIV-seronegative (SN) nondemented, community-dwelling participants underwent DTI to derive whole-brain measures of white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]). For each participant, the white matter T2 volume was thresholded to remove regions of abnormal signal, resulting in a NAWM mask, which was then applied to the FA and MD volumes to extract voxel-wise NAWM measures of white matter integrity. Voxel-wise group comparisons of FA and MD were conducted (P < 0.005, extent threshold 5 voxels) while controlling for age and substance-abuse history. RESULTS: There were no significant differences between the groups for demographic or cognitive performance variables. Summary whole-brain measures of FA and MD were equivalent between the SP and SN samples. Among the SP sample, history of substance abuse was associated with significantly increased whole-brain NAWM MD, and coinfection with hepatitis C virus (HCV) was associated with a trend for increased MD. Correlations between whole-brain NAWM FA and MD with cognitive performance measures were not significant. Regional analyses of DTI measures revealed variable differences in NAWM FA in the SP sample, with findings of both decreased and increased FA. Differences in NAWM MD were more consistent, with widespread increases noted in the SP sample compared to the SN sample. Eight of the 10 regions displaying significantly increased FA in the SP sample were also found to have significantly increased MD compared to the SN sample. CONCLUSIONS: Decreased white matter integrity is present even in radiologically defined NAWM in nondemented, community-dwelling patients with HIV. The decrease in NAWM integrity is best seen in increases in MD, a measure of generalized tissue breakdown. Indications of NAWM axonal integrity (FA) present a more complicated picture, with both decreased FA and increased FA in the SP sample. Our findings of variable HIV-associated FA changes in NAWM may account for previous conflicting reports of changes in DTI parameters in this population. The results of our study suggest that HIV infection contributes to variable changes in DTI values, reflecting both direct loss of axonal integrity and a loss of complexity to the underlying axonal matrix.

Native valve endocarditis due to Gordonia polyisoprenivorans: case report and review of literature of bloodstream infections caused by Gordonia species.

We report the first case of endocarditis caused by Gordonia polyisoprenivorans and concisely review the English literature regarding bloodstream infections caused by Gordonia species.

Triple-nucleoside analog antiretroviral therapy: is there still a role in clinical practice? A review.

The development and widespread clinical use of coformulated abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) as Trizivir represented an important advance in the management of HIV-infected patients, especially those with adherence challenges. With a low pill burden, no food restrictions, limited drug-drug interactions, and a favorable resistance profile, ABC/3TC/ZDV remains an alternative option in the US Department of Health and Human Services Consensus Panel Guidelines as initial treatment in antiretroviral-naive patients. Recent data have shown ABC/3TC/ZDV to be less efficacious in suppressing and/or maintaining suppression of virologic replication compared with efavirenz-containing antiretroviral therapy. Although triple-nucleoside/nucleotide reverse transcriptase inhibitor (t-NRTI) combinations that do not contain a thymidine analog (ZDV or stavudine) have recently shown high virologic failure rates in clinical trials and clinical practice, t-NRTI regimens containing a thymidine analog have consistently been shown to be efficacious.

Short-term safety and pharmacodynamics of amdoxovir in HIV-infected patients.

OBJECTIVES: To evaluate the pharmacodynamics and safety of escalating doses of amdoxovir (DAPD) monotherapy administered to treatment-naive and experienced HIV-1-infected patients over 15 days. DESIGN: Ninety patients with plasma HIV-1 RNA levels between 5000 and 250,000 copies/ml were randomized to DAPD 25, 100, 200, 300 or 500 mg twice daily or 600 mg once daily monotherapy [antiretroviral therapy (ART)-naive and ART-experienced] or to add DAPD 300 or 500 mg twice daily to existing ART. After 15 days of dosing, patients were followed for an additional 7 days. METHODS: Antiviral activity was compared between treatment arms using log10 HIV-1 RNA based on average area under the curve minus baseline to day 15. Safety and tolerability was analyzed by incidence of grade 1 to 4 clinical and laboratory adverse events. RESULTS: In ART-naive patients receiving short-term DAPD monotherapy, a median reduction in plasma HIV-1 RNA of 1.5 log10 copies/ml at the highest doses was observed. In ART-experienced patients, the reduction in viral load observed at each dose was less than that observed in treatment-naive patients (reduction of 0.7 log10 at 500 mg twice daily). The incidence of adverse events was similar across groups with the majority of adverse events reported as mild or moderate in severity. Steady-state plasma concentrations of DAPD and dioxolane guanosine followed linear kinetics. CONCLUSIONS: DAPD was well tolerated and produced antiviral activity in treatment-naive and in some treatment-experienced patients. In ART-experienced patients, the antiviral activity was significant in those with no thymidine-analogue mutations and higher baseline CD4+ cell counts.

Monitoring processed, mature Human Immunodeficiency Virus type 1 particles immediately following treatment with a protease inhibitor-containing treatment regimen.

Protease inhibitors (PIs) block HIV-1 maturation into an infectious virus particle by inhibiting the protease processing of gag and gag-pol precursor proteins. We have used a simple anti-HIV-1 p24 Western blot to monitor the processing of p55gag precursor into the mature p24 capsid immediately following the first dosage of a PI-containing treatment regimen. Evidence of PI activity was observed in plasma virus as early as 72 hours post treatment-initiation and was predictive of plasma viral RNA decrease at 4 weeks.