Dynamic changes in gene expression and signalling during trophoblast development in the horse

Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes and pathways that regulate chorionic girdle trophoblast development. Our aim was to identify genes and signalling pathways active in vivo in equine chorionic girdle trophoblast within a critical 7-days window. We exploited the late implantation of the equine conceptus to obtain trophoblast tissue. An Agilent equine 44K microarray was performed using RNA extracted from chorionic girdle and chorion (control) from equine pregnancy days 27, 30, 31 and 34 (n = 5), corresponding to the initiation of chorionic girdle trophoblast proliferation, differentiation and migration. Data were analysed using R packages limma and maSigPro, Ingenuity Pathway Analysis and DAVID and verified using qRT-PCR, promoter analysis, western blotting and migration assays. Microarray analysis showed gene expression (absolute log FC >2, FDR-adjusted P < 0.05) was rapidly and specifically induced in the chorionic girdle between days 27 and 34 (compared to day 27, day 30 = 116, day 31 = 317, day 34 = 781 genes). Pathway analysis identified 35 pathways modulated during chorionic girdle development (e.g. FGF, integrin, Rho GTPases, MAPK) including pathways that have limited description in mammalian trophoblast (e.g. IL-9, CD40 and CD28 signalling). Rho A and ERK/MAPK activity was confirmed as was a role for transcription factor ELF5 in regulation of the CGB promoter. The purity and accessibility of chorionic girdle trophoblast proved to be a powerful resource to identify candidate genes and pathways involved in early equine placental development.

Convergent evolution of pregnancy-specific glycoproteins in human and horse.

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions.

Assessing Problematic Substance Use in HIV Care: Which Questions Elicit Accurate Patient Disclosures?

BACKGROUND: Substance use is associated with higher rates of antiretroviral non-adherence and poor HIV outcomes. This study examined how HIV care providers assess substance use, and which questions elicit accurate patient disclosures. METHODS: We conducted a conversation analysis of audio-recorded encounters between 56 providers and 162 patients living with HIV (PLWH) reporting active substance use in post-encounter interviews (cocaine or heroin use in the past 30 days, > 4 days intoxicated in past 30 days, or AUDIT score ≥ 8). We assessed the frequency of substance use discussion, characterized the types of questions used by providers, and determined the frequency of accurate patient disclosure by question type. RESULTS: In 55 reports of active substance use, providers already knew about the use (n = 16) or patients disclosed unpromptednn = 39). Among the remaining 155 instances of substance use in which providers had the opportunity to elicit disclosure, 78 reports (50 %) of substance use were not discussed. Of the remaining 77 reports in which the provider asked about substance use, 55 (71 %) patients disclosed and 22 (29 %) did not disclose. Questions were classified as: open-ended (n = 18, "How's the drinking going?"); normalizing (n = 14, "When was the last time you used?"); closed-ended (n = 36, "Have you used any cocaine?"); leading towards non-use (n = 9, "Have you been clean?"). Accurate disclosure followed 100 % of open-ended and normalizing questions, 58 % of closed-ended questions, and 22 % of leading questions. After adjusting for drug type, closed-ended questions were 41 % less likely (p < 0.001), and 'leading' questions 78 % less likely (p = 0.016) than broad and normalizing questions to elicit disclosures. CONCLUSION: Providers in this sample missed almost half of the opportunities to identify and discuss substance use with PLWH. Providers can increase the probability of patient disclosure by using open-ended or normalizing questions that ask about the "last time" that the patient used drugs or alcohol.

Linguistic and Cultural Adaptation of a Computer-Based Counseling Program (CARE+ Spanish) to Support HIV Treatment Adherence and Risk Reduction for People Living With HIV/AIDS: A Randomized Controlled Trial.

BACKGROUND: Human immunodeficiency virus (HIV) disease in the United States disproportionately affects minorities, including Latinos. Barriers including language are associated with lower antiretroviral therapy (ART) adherence seen among Latinos, yet ART and interventions for clinic visit adherence are rarely developed or delivered in Spanish. OBJECTIVE: The aim was to adapt a computer-based counseling tool, demonstrated to reduce HIV-1 viral load and sexual risk transmission in a population of English-speaking adults, for use during routine clinical visits for an HIV-positive Spanish-speaking population (CARE+ Spanish); the Technology Acceptance Model (TAM) was the theoretical framework guiding program development. METHODS: A longitudinal randomized controlled trial was conducted from June 4, 2010 to March 29, 2012. Participants were recruited from a comprehensive HIV treatment center comprising three clinics in New York City. Eligibility criteria were (1) adults (age ≥18 years), (2) Latino birth or ancestry, (3) speaks Spanish (mono- or multilingual), and (4) on antiretrovirals. Linear and generalized mixed linear effects models were used to analyze primary outcomes, which included ART adherence, sexual transmission risk behaviors, and HIV-1 viral loads. Exit interviews were offered to purposively selected intervention participants to explore cultural acceptability of the tool among participants, and focus groups explored the acceptability and system efficiency issues among clinic providers, using the TAM framework. RESULTS: A total of 494 Spanish-speaking HIV clinic attendees were enrolled and randomly assigned to the intervention (arm A: n=253) or risk assessment-only control (arm B, n=241) group and followed up at 3-month intervals for one year. Gender distribution was 296 (68.4%) male, 110 (25.4%) female, and 10 (2.3%) transgender. By study end, 433 of 494 (87.7%) participants were retained. Although intervention participants had reduced viral loads, increased ART adherence and decreased sexual transmission risk behaviors over time, these findings were not statistically significant. We also conducted 61 qualitative exit interviews with participants and two focus groups with a total of 16 providers. CONCLUSIONS: A computer-based counseling tool grounded in the TAM theoretical model and delivered in Spanish was acceptable and feasible to implement in a high-volume HIV clinic setting. It was able to provide evidence-based, linguistically appropriate ART adherence support without requiring additional staff time, bilingual status, or translation services. We found that language preferences and cultural acceptability of a computer-based counseling tool exist on a continuum in our urban Spanish-speaking population. Theoretical frameworks of technology's usefulness for behavioral modification need further exploration in other languages and cultures. TRIAL REGISTRATION: ClinicalTrials.gov NCT01013935; https://clinicaltrials.gov/ct2/show/NCT01013935 (Archived by WebCite at http://www.webcitation.org/6ikaD3MT7).

Hospitalization Rates and Reasons Among HIV Elite Controllers and Persons With Medically Controlled HIV Infection.

BACKGROUND: Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV. METHODS: For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ≥350 cells/mm(2) were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic category-specific hospitalization rates were compared between groups using negative binomial regression. RESULTS: We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 [95% confidence interval, 1.21-2.60]), cardiovascular (3.19 [1.50-6.79]) and psychiatric (3.98 [1.54-10.28]) hospitalization than was medical control. Non-AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%). CONCLUSIONS: Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor.

Provider-patient communication about adherence to anti-retroviral regimens differs by patient race and ethnicity.

Disparities in HIV care and outcomes negatively affect Black and Hispanic patients. Features of clinical communication may be a factor. This study is based on coding transcripts of 404 routine outpatient visits by people with HIV at four sites, using a validated system. In models adjusting for site and patient characteristics, with provider as a random effect, providers were more "verbally dominant" with Black patients than with others. There was more discussion about ARV adherence with both Black and Hispanic patients, but no more discussion about strategies to improve adherence. Providers made more directive utterances discussing ARV treatment with Hispanic patients. Possible interpretations of these findings are that providers are less confident in Black and Hispanic patients to be adherent; that they place too much confidence in their White, non-Hispanic patients; or that patients differentially want such discussion. The lack of specific problem solving and high provider directiveness suggests areas for improvement.

Increased rates of rapid point-of-care HIV testing using patient care technicians to perform tests in the ED.

BACKGROUND: Various emergency department (ED) HIV testing models are reported in the literature but may not all be sustainable. We sought to determine whether changing an ED rapid HIV testing program from counselor-based to ED technician-based resulted in more testing. METHODS: We evaluated data from an ED rapid HIV testing program. Triage nurses offered testing to patients. In 2009, counselors performed rapid testing weekdays from 10:00 am to 6:00 pm. In 2010, ED technicians were trained to perform the test and replaced counselors. We compared the numbers of tests performed during the same 6-month periods in 2009 and 2010. Study personnel abstracted results through medical record review. RESULTS: A total of 241 oral tests were performed in 2009 compared with 1483 in 2010, representing slightly more than a 6-fold increase. In 2010, there was a steady increase in testing month by month. Incorporating patient volume, testing rates increased from 1.3% to 8.1%. Oral testing yielded no positive test results in 2009, but 7 individuals (0.47%) tested newly positive during the testing period of 2010. Of those with a documented CD4 count within 100 days of the positive result, 4 of 5 had CD4 counts less than 200. CONCLUSIONS: We present a novel approach to HIV testing using existing staff within the ED. This new ED technician-based model led to large increases in rates of testing.

Urinalysis: case presentations for the primary care physician.

Urinalysis is useful in diagnosing systemic and genitourinary conditions. In patients with suspected microscopic hematuria, urine dipstick testing may suggest the presence of blood, but results should be confirmed with a microscopic examination. In the absence of obvious causes, the evaluation of microscopic hematuria should include renal function testing, urinary tract imaging, and cystoscopy. In a patient with a ureteral stent, urinalysis alone cannot establish the diagnosis of urinary tract infection. Plain radiography of the kidneys, ureters, and bladder can identify a stent and is preferred over computed tomography. Asymptomatic bacteriuria is the isolation of bacteria in an appropriately collected urine specimen obtained from a person without symptoms of a urinary tract infection. Treatment of asymptomatic bacteriuria is not recommended in nonpregnant adults, including those with prolonged urinary catheter use.

Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

BACKGROUND: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. METHODS: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. RESULTS: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. CONCLUSION: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. LEVEL OF EVIDENCE: Level III, Therapeutic Care Management.

Regulation of glucocorticoid metabolism in the boar testis and caput epididymidis by the gonadotrophin-cAMP signalling pathway.

In target tissues, cortisol is metabolised by two 11ß-hydroxysteroid dehydrogenase (11ßHSD) isoenzymes, namely 11ßHSD1 and 11ßHSD2, both of which are co-expressed in the boar testis and reproductive tract. The present study has assessed whether cortisol-cortisone metabolism in boar testis and caput epididymidis can be regulated via the gonadotrophin-cAMP signalling pathway. 11ßHSD activities were measured by using a radiometric conversion assay in static tissue culture. In both testis and caput epididymidis, the net reduction of cortisone but not the net oxidation of cortisol, was significantly decreased by luteinising hormone (by 53 ± 20% and 45 ± 9%, respectively, P < 0.05), forskolin (by 60 ± 7% and 57 ± 9%, respectively, P < 0.01) and 8-bromo-cAMP (by 54 ± 4% and 64 ± 1%, respectively, P < 0.01). This suppression of 11-ketosteroid reductase activity in the boar testis by forskolin could be attenuated by the protein kinase A (PKA) inhibitor, H89. Hence, within the boar testis and the caput epididymidis, the local actions of glucocorticoids are modulated by gonadotrophin-cAMP-PKA signalling via their selective effects on the reductase activity of 11ßHSD.

Patient activation and improved outcomes in HIV-infected patients.

BACKGROUND: The Patient Activation Measure (PAM) assesses several important concepts in chronic care management, including self-efficacy for positive health behaviors. In HIV-infected populations, better self-efficacy for medication management is associated with improved adherence to antiretroviral medications (ARVs), which is critically important for controlling symptoms and slowing disease progression. OBJECTIVE: To determine 1) characteristics associated with patient activation and 2) associations between patient activation and outcomes in HIV-infected patients. DESIGN: Cross-sectional survey. PARTICIPANTS: 433 patients receiving care in four HIV clinics. METHODS: An interviewer conducted face-to-face interviews with patients following their HIV clinic visit. Survey data were supplemented with medical record abstraction to obtain most recent CD4 counts, HIV viral load and antiretroviral medications. MAIN MEASURES: Patient activation was measured using the 13-item PAM (possible range 0-100). Outcomes included CD4 cell count > 200 cells/mL(3), HIV-1 RNA < 400 copies/mL (viral suppression), and patient-reported adherence. KEY RESULTS: Overall, patient activation was high (mean PAM = 72.3 [SD 16.5, range 34.7-100]). Activation was lower among those without vs. with a high school degree (68.0 vs. 74.0, p < .001), and greater depression (77.6 lowest, 70.2 middle, 68.1 highest tertile, p < .001). There was no association between patient activation and age, race, gender, problematic alcohol use, illicit drug use, or social status. In multivariable models, every 5-point increase in PAM was associated with greater odds of CD4 count > 200 cells/mL(3) (aOR 1.10 [95 % CI 1.01, 1.21]), adherence (aOR 1.18 [95 % CI 1.09, 1.29]) and viral suppression (aOR 1.08 [95 % CI 1.00, 1.17]). The association between PAM and viral suppression was mediated through adherence. CONCLUSIONS: Higher patient activation was associated with more favorable HIV outcomes. Interventions to improve patient activation should be developed and tested for their ability to improve HIV outcomes.

Primary care provider cultural competence and racial disparities in HIV care and outcomes.

BACKGROUND: Health professional organizations have advocated for increasing the "cultural competence" (CC) of healthcare providers, to reduce racial and ethnic disparities in patient care. It is unclear whether provider CC is associated with more equitable care. OBJECTIVE: To evaluate whether provider CC is associated with quality of care and outcomes for patients with HIV/AIDS. DESIGN AND PARTICIPANTS: Survey of 45 providers and 437 patients at four urban HIV clinics in the U.S. MAIN MEASURES: Providers' self-rated CC was measured using a novel, 20-item instrument. Outcome measures included patients' receipt of antiretroviral (ARV) therapy, self-efficacy in managing medication regimens, complete 3-day ARV adherence, and viral suppression. KEY RESULTS: Providers' mean age was 44 years; 56 % were women, and 64 % were white. Patients' mean age was 45; 67 % were men, and 77 % were nonwhite. Minority patients whose providers scored in the middle or highest third on self-rated CC were more likely than those with providers in the lowest third to be on ARVs, have high self-efficacy, and report complete ARV adherence. Racial disparities were observed in receipt of ARVs (adjusted OR, 95 % CI for white vs. nonwhite: 6.21, 1.50-25.7), self-efficacy (3.77, 1.24-11.4), and viral suppression (13.0, 3.43-49.0) among patients of low CC providers, but not among patients of moderate and high CC providers (receipt of ARVs: 0.71, 0.32-1.61; self-efficacy: 1.14, 0.59-2.22; viral suppression: 1.20, 0.60-2.42). CONCLUSIONS: Provider CC was associated with the quality and equity of HIV care. These findings suggest that enhancing provider CC may reduce racial disparities in healthcare quality and outcomes.

Epididymal protein Rnase10 is required for post-testicular sperm maturation and male fertility.

Eutherian spermatozoa are dependent on the environment of the proximal epididymis to complete their maturation; however, no specific epididymal factors that mediate this process have so far been identified. Here, we show that targeted disruption of the novel gene Rnase10 encoding a secreted proximal epididymal protein in the mouse results in a binding defect in spermatozoa and their inability to pass through the uterotubal junction in the female. The failure to gain the site of fertilization in the knockout spermatozoa is associated with a gradual loss of ADAM3 and ADAM6 proteins during epididymal transit. In the distal epididymis, these spermatozoa appear to lack calcium-dependent associations with the immobilizing glutinous extracellular material and are released as single, vigorously motile cells that display no tendency for head-to-head agglutination and lack affinity to the oviductal epithelium. In sperm-egg binding assay, they are unable to establish a tenacious association with the zona pellucida, yet they are capable of fertilization. Furthermore, these sperm show accelerated capacitation resulting in an overall in vitro fertilizing ability superior to that of wild-type sperm. We conclude that the physiological role of sperm adhesiveness is in the mechanism of restricted sperm entry into the oviduct rather than in sperm-egg interaction.

A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3.

We tested the principle of treating malignant ovarian tumors by vaccination against their ectopically expressed protein, zona pellucida glycoprotein (ZP) 3, using as the experimental model the granulosa cell tumors that develop in transgenic mice expressing the simian virus 40 T-antigen under the inhibin-α promoter (inhα/Tag). We found high ZP3 expression in granulosa cell tumors of the transgenic mice, in human surface ovarian cancer and granulosa cell lines, and in human granulosa cell tumors and their metastases. Early preventive immunization (between 2 and 5.5 mo of age) of transgenic mice with recombinant human (rh) ZP3 prevented ovarian tumorigenesis, and delayed therapeutic immunization (between 4.5 and 7 mo) reduced weights of existing tumors by 86 and 75%, respectively (P<0.001), compared to vehicle-treated control mice. No objective side effects of the immunizations were observed. Liver metastases were found in nontreated/vehicle-treated controls (n=7/39), but none following active rhZP3 immunizations (n=0/36; P<0.05). Immunization with rhZP3 was highly effective, as demonstrated by the induction of anti-ZP3 antibodies, as well as proliferative responses to the ZP3 antigen. These results signal rhZP3 immunization as a novel strategy to be developed for the immunotherapy of ovarian granulosa cell tumors, as well as for that of other malignancies that may express ZP3.

A multicenter study of physician mindfulness and health care quality.

PURPOSE: Mindfulness (ie, purposeful and nonjudgmental attentiveness to one's own experience, thoughts, and feelings) is associated with physician well-being. We sought to assess whether clinician self-rated mindfulness is associated with the quality of patient care. METHODS: We conducted an observational study of 45 clinicians (34 physicians, 8 nurse practitioners, and 3 physician assistants) caring for patients infected with the human immunodeficiency virus (HIV) who completed the Mindful Attention Awareness Scale and 437 HIV-infected patients at 4 HIV specialty clinic sites across the United States. We measured patient-clinician communication quality with audio-recorded encounters coded using the Roter Interaction Analysis System (RIAS) and patient ratings of care. RESULTS: In adjusted analyses comparing clinicians with highest and lowest tertile mindfulness scores, patient visits with high-mindfulness clinicians were more likely to be characterized by a patient-centered pattern of communication (adjusted odds ratio of a patient-centered visit was 4.14; 95% CI, 1.58-10.86), in which both patients and clinicians engaged in more rapport building and discussion of psychosocial issues. Clinicians with high-mindfulness scores also displayed more positive emotional tone with patients (adjusted ß = 1.17; 95% CI, 0.46-1.9). Patients were more likely to give high ratings on clinician communication (adjusted prevalence ratio [APR] = 1.48; 95% CI, 1.17-1.86) and to report high overall satisfaction (APR = 1.45; 95 CI, 1.15-1.84) with high-mindfulness clinicians. There was no association between clinician mindfulness and the amount of conversation about biomedical issues. CONCLUSIONS: Clinicians rating themselves as more mindful engage in more patient-centered communication and have more satisfied patients. Interventions should determine whether improving clinician mindfulness can also improve patient health outcomes.

Alcohol use, anal sex, and other risky sexual behaviors among HIV-infected women and men.

Effective sexual risk reduction strategies for HIV-infected individuals require an understanding of alcohol's influence on specific sexual behaviors. We conducted audio-computer-assisted-self-interviews on 910 patients from two HIV primary care programs. The association between alcohol use and risky sexual behaviors was examined using multivariable logistic regression adjusting for age, education, race/ethnicity and drug use. Frequent/binge drinking was associated with engaging in anal sex and having multiple sex partners among women, engaging in insertive anal sex among gay/bisexual men, and was unrelated to risky sexual behaviors among heterosexual men. Infrequent drinkers did not differ in sexual risk behaviors from abstainers among women or men. Finally, there was no interaction effect between race/ethnicity and alcohol use on the association with sexual risk behaviors. The study has yielded important new findings in several key areas with high relevance to HIV care. Results underscore the importance of routinely screening for alcohol use and risky sexual behaviors in HIV primary care.

Provider-patient adherence dialogue in HIV care: results of a multisite study.

Few studies have analyzed physician-patient adherence dialogue about ARV treatment in detail. We comprehensively describe physician-patient visits in HIV care, focusing on ARV-related dialogue, using a system that assigns each utterance both a topic code and a speech act code. Observational study using audio recordings of routine outpatient visits by people with HIV at specialty clinics. Providers were 34 physicians and 11 non-M.D. practitioners. Of 415 patients, 66% were male, 59% African-American. 78% reported currently taking ARVs. About 10% of utterances concerned ARV treatment. Among those using ARVs, 15% had any adherence problem solving dialogue. ARV problem solving talk included significantly more directives and control parameter utterances by providers than other topics. Providers were verbally dominant, asked five times as many questions as patients, and made 21 times as many directive utterances. Providers asked few open questions, and rarely checked patients' understanding. Physicians respond to the challenges of caring for patients with HIV by adopting a somewhat physician-centered approach which is particularly evident in discussions about ARV adherence.

Developing PeerLink to engage out-of-care HIV+ substance users: training peers to deliver a peer-led motivational intervention with fidelity.

Substance use among HIV+ individuals can be a barrier to HIV care, resulting in poor health outcomes. Motivational interviewing (MI) is an effective intervention to reduce substance abuse and increase HIV-related health. Healthcare workers from various backgrounds can be effectively trained in delivering MI interventions; however, there has been limited evidence that peers can effectively deliver MI interventions with fidelity. Peers have traditionally worked in HIV care settings and represent a valid context for a peer-delivered intervention focused on motivational issues. We trained four peers in MI. In this paper, we describe the intervention, explain the MI training methods, and investigate whether peers can be trained in MI with fidelity. The MI training included didactic instruction, group workshops, and individual feedback sessions. Two of four peers achieved MI treatment fidelity as measured by the Motivational Interviewing Treatment Integrity Code Version 3.0. Overall, peers had difficulty using open-ended questions and querying pros and cons, skills thought necessary to elicit change talk. They also tended to give too much direct advice where reflections would have been appropriate. A challenge was training peers to change familiar ways of communicating. Nonetheless, they did well at assessing and highlighting motivation to change. The total training hours (40 h) was long compared with other published MI studies. However, the intervention included several components with two targeted change behaviors. It is likely that peers can be trained in MI with fidelity in less time given a more streamlined intervention. When working with peers who have life stressors similar to the target group, it is important to be flexible in the training.

The impact of depressive symptoms on patient-provider communication in HIV care.

Persons with HIV who develop depression have worse medical adherence and outcomes. Poor patient-provider communication may play a role in these outcomes. This cross-sectional study evaluated the influence of patient depression on the quality of patient-provider communication. Patient-provider visits (n=406) at four HIV care sites were audio-recorded and coded with the Roter Interaction Analysis System (RIAS). Negative binomial and linear regressions using generalized estimating equations tested the association of depressive symptoms, as measured by the Center for Epidemiology Studies Depression scale (CES-D), with RIAS measures and postvisit patient-rated quality of care and provider-reported regard for his or her patient. The patients, averaged 45 years of age (range =20-77), were predominately male (n=286, 68.5%), of black race (n=250, 60%), and on antiretroviral medications (n=334, 80%). Women had greater mean CES-D depression scores (12.0) than men (10.6; p=0.03). There were no age, race, or education differences in depression scores. Visits with patients reporting severe depressive symptoms compared to those reporting none/mild depressive symptoms were longer and speech speed was slower. Patients with severe depressive symptoms did more emotional rapport building but less social rapport building, and their providers did more data gathering/counseling (ps<0.05). In postvisit questionnaires, providers reported lower levels of positive regard for, and rated more negatively patients reporting more depressive symptoms (p<0.01). In turn, patients reporting more depressive symptoms felt less respected and were less likely to report that their provider knows them as a person than none/mild depressive symptoms patients (ps<0.05). Greater psychosocial needs of patients presenting with depressive symptoms and limited time/resources to address these needs may partially contribute to providers' negative attitudes regarding their patients with depressive symptoms. These negative attitudes may ultimately serve to adversely impact patient-provider communication and quality of HIV care.

Assessment of asymptomatic microscopic hematuria in adults.

Although routine screening for bladder cancer is not recommended, microscopic hematuria is often incidentally discovered by primary care physicians. The American Urological Association has published an updated guideline for the management of asymptomatic microscopic hematuria, which is defined as the presence of three or more red blood cells per high-power field visible in a properly collected urine specimen without evidence of infection. The most common causes of microscopic hematuria are urinary tract infection, benign prostatic hyperplasia, and urinary calculi. However, up to 5% of patients with asymptomatic microscopic hematuria are found to have a urinary tract malignancy. The risk of urologic malignancy is increased in men, persons older than 35 years, and persons with a history of smoking. Microscopic hematuria in the setting of urinary tract infection should resolve after appropriate antibiotic treatment; persistence of hematuria warrants a diagnostic workup. Dysmorphic red blood cells, cellular casts, proteinuria, elevated creatinine levels, or hypertension in the presence of microscopic hematuria should prompt concurrent nephrologic and urologic referral. The upper urinary tract is best evaluated with multiphasic computed tomography urography, which identifies hydronephrosis, urinary calculi, and renal and ureteral lesions. The lower urinary tract is best evaluated with cystoscopy for urethral stricture disease, benign prostatic hyperplasia, and bladder masses. Voided urine cytology is no longer recommended as part of the routine evaluation of asymptomatic microscopic hematuria, unless there are risk factors for malignancy.