Early stroke post-heart transplant is associated with decreased survival in children.

BACKGROUND: Major neurologic events (MNEs) after heart transplantation (HTx) and their effect on survival have not been well described in children. In this study we aimed to characterize early MNEs (stroke, isolated seizures not from stroke and posterior reversible leukoencephalopathy [PRES] within 1 year after primary pediatric HTx) and evaluate their impact on 1-year post-HTx survival. We hypothesized that early an MNE after HTx is associated with decreased 1-year patient survival. METHODS: We performed a pediatric, single-center, retrospective analysis of 345 consecutive patients aged 0 to 22 years who underwent primary HTx during the period from November 1, 1994 to October 31, 2015. Characteristics were compared between patients with and without early MNEs. RESULTS: Nineteen percent (65 of 345) of patients had an MNE within 1 year after HTx (median 9 days, interquartile range [IQR] 4 to 23 days). Freedom from early MNE was 97%, 85% and 80% at 1, 6 and 12 months, respectively. Of the total 65 events, stroke comprised 55.4% (n = 36), isolated seizure 29.2% (n = 19) and PRES 15.4% (n = 10). With multiple logistic regression, previous neurologic disease, infection requiring intravenous antibiotic therapy and post-operative drug-treated hypertension were found to be significant risk factors for early MNEs. Stroke (hazard ratio 4.1, IQR 2.3 to 7.6, p < 0.0001), but not seizures and PRES, was associated with decreased 1-year patient survival. CONCLUSIONS: Major neurologic events are common after pediatric HTx and usually occur within the first few weeks. Early stroke was associated with decreased 1-year survival. Potentially modifiable factors, including prior neurologic event, drug-treated hypertension and infection, were associated with increased risk of developing early MNEs.

HIV-infected individuals with high coping self-efficacy are less likely to report depressive symptoms: a cross-sectional study from Denmark.

OBJECTIVES: Having effective ways to cope helps HIV-infected individuals maintain good psychological and physical well-being. This study investigated the relationship between coping self-efficacy levels, as determined by the Coping Self-Efficacy Scale (CSE), HIV status disclosure, and depression in a Danish cohort. METHODS: In 2008, the CSE was administered to 304 HIV-infected individuals to measure their confidence in their ability to cope with HIV infection. HIV status disclosure was assessed on a three-point scale: living openly with the disease, partly openly, or secretly. The Beck Depression Inventory (BDI) was used to assess depression prevalence and severity. RESULTS: The CSE score was significantly related to depression (Spearman's rho = -0.71; the test of H0: BDI and coping, probability >t=0.0001). There was a significant relationship between higher CSE scores and living openly with HIV. The risk of depression was four times higher in HIV-infected individuals who did not disclose their HIV status (i.e. who lived 'secretly'; odds ratio = 4.1) than in individuals who lived openly. CONCLUSION: Those with low CSE scores were more likely to report living secretly with HIV and to be depressed. Disclosing HIV may constitute a social stressor, and a lack of coping self-efficacy may increase the likelihood of non-disclosure and depression. Interventions that enhance self-efficacy may help in managing the demands of daily life with HIV, increase disclosure, and reduce depression.

A randomized comparison of two instruments for measuring self-reported antiretroviral adherence.

A randomised trial compared two instruments for assessing self-reported adherence to antiretroviral medications: (1) a day-by-day recall instrument that elicited the number of missed doses in each of the prior three days (3-day instrument; n=64) and (2) a general recall instrument that elicited an estimate of proportion of pills taken during the prior seven days (7-day instrument; n=70). Adherence was measured at study visits over 12 months among participants in a clinical trial assessing treatment strategies for individuals with virologic failure and multidrug-resistant HIV. Participants had a median (interquartile range) of 133 (41-264) CD4 cells/ml(3) and a median of 10 major HIV resistance mutations at baseline. Mean adherence levels were 90-98% throughout the study. There was a greater trend in the likelihood of 100% adherence when measured by the 3-day versus the 7-day instrument (odds ratio (OR)=1.45; p=0.06). The likelihood of consistent 100% adherence measured by either instrument decreased over time (p<0.001). Participants reporting 100% adherence at more than half of study visits had better virologic and immunologic outcomes at month-12 compared to those reporting 100% adherence at half or fewer visits (HIV RNA decline of 0.96 versus 0.51 log, respectively, p=0.02; and CD4 cell increase of 51.0 versus 17.8 cells, p=0.04). This study demonstrated the utility of the general 7-day recall adherence self-report instrument as well as the 3-day day-by-day recall adherence self-report instrument for measuring antiretroviral adherence. Self-reported adherence was significantly associated with virologic and immunologic outcomes in this population with advanced drug-resistant HIV disease.

Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence.

This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ARTadherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4+ cell count 230 cells/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p < 0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with < 80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained.

Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study.

BACKGROUND: Effective interventions are needed to prevent acquisition of HIV infection in men who have sex with men. To date, no behavioural interventions specifically for this risk group have been tested with HIV infection as the primary outcome. METHODS: This multisite two-group randomised controlled phase IIb trial tested the efficacy of a behavioural intervention in preventing HIV infection among 4295 men who have sex with men. The experimental intervention consisted of ten one-on-one counselling sessions followed by maintenance sessions every 3 months. The standard condition was twice-yearly Project RESPECT individual counselling. Twice-yearly follow-up visits included testing for HIV antibody and assessment of behavioural outcomes. FINDINGS: The rate of acquisition of HIV infection was 18.2% (95% CI -4.7 to 36.0) lower in the intervention group than the standard group. Adjustment for baseline covariates attenuated the intervention effect to 15.7% (-8.4 to 34.4). The effect was more favourable in the first 12-18 months of follow-up. The occurrence of unprotected receptive anal intercourse with HIV-positive and unknown-status partners was 20.5% (10.9 to 29.0) lower in the intervention than in the standard group. INTERPRETATION: The results from the primary analyses allow us to rule out that the experimental intervention is associated with a 35% lower rate of HIV acquisition than in the standard group. The overall estimate of a difference of 18.2%, more favourable estimates of effect in the first 12-18 months, and similar effects on risk behaviours suggest that prevention of HIV infection among men who have sex with men by a behavioural intervention is feasible. Further work should be done to develop more effective interventions.

Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.

SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

Failure to maintain adherence to HAART in a cohort of French HIV-positive injecting drug users.

The study, carried out in the French MANIF 2000 cohort of HIV positive patients contaminated through injecting drug use, assessed the impact of patients' sociodemographic and psychological characteristics, behaviors toward drug abuse, and antiretroviral treatment characteristics on the maintenance of adherence to HAART (highly active antiretroviral therapies). A total of 96 patients (30 men and 66 women), who were initially adherent at their first visit after HAART prescription, were considered for analysis. Among these 96 patients, 22 (22.9%) experienced adherence failure defined as a self-reported, non-adherence behavior at any visit before the 18th month of treatment. Logistic regression showed that lack of a stable relationship, active drug injection, and depression were independently associated with adherence failure. Patients' counseling for facilitating maintenance of adherence to HAART over time should focus on prevention of drug use, provision of social support and consider the potential impact of difficulties with treatment on psychological well-being.

What happened to home HIV test collection kits? Intent to use kits, actual use, and barriers to use among persons at risk for HIV infection.

Through sequential cross-sectional surveys, we examined intent to use home HIV test collection kits, actual use and barriers to use among persons at high risk for HIV infection. Interest in kits was assessed in the 1995-96 HIV Testing Survey (HITS, n=1683). Kit use, knowledge of kits and barriers to use were assessed in the 1998-99 HITS (n=1788), after kits had become widely available. When asked to choose among future testing options, 19% of 1995-96 participants intended to use kits. Untested participants were more likely than previously tested HIV-negative participants to choose kits for their next HIV test (p < 0.001). Among 1998-99 participants, only 24 (1%) had used kits; 46% had never heard of kits. Predictors of not knowing about kits included never having been HIV tested and black or Latino race. Common reasons for not using kits among participants aware of home test kits were concerns about accuracy, lack of in-person counselling and cost. Despite high rates of anticipated use, kits have had minimal impact on the testing behaviour of persons at high risk for HIV infection. Increasing awareness of kits, reducing price and addressing concerns about kit testing procedures may increase kit use, leading to more HIV testing by at-risk individuals.

Postexposure prophylaxis for human immunodeficiency virus infection after sexual or injection drug use exposure: identification and characterization of the source of exposure.

In a nonrandomized study of nonoccupational postexposure prophylaxis (PEP), a cross-sectional evaluation of subjects who were the source of human immunodeficiency (HIV) exposure was performed to characterize partners of index subjects seeking nonoccupational PEP against HIV. Among 401 index subjects, 64 (16%) recruited a source subject. Those in a steady relationship and those who knew that the source subject was HIV antibody positive were more likely to recruit their source subject. Source subjects reported high rates of past (78%) and current (69%) antiretroviral use; 46% of those using antiretroviral drugs had detectable plasma HIV-1 RNA levels. Antiretroviral resistance was detected in many source subjects who reported any use of antiretrovirals and was rare among source subjects who reported no history of antiretroviral use. Clinicians often make treatment decisions on the basis of incomplete knowledge of the source subject's HIV status or antiretroviral treatment history. The treatment history, particularly nonuse of a class of antiretroviral drugs, can be used to predict drug resistance.

Development and validation of a self-completed HIV symptom index.

Traditional, open-ended provider questions regarding patient symptoms are insensitive. Better methods are needed to measure symptoms for clinical management, patient-oriented research, and adverse drug-event reporting. Our objective was to develop and initially validate a brief, self-reported HIV symptom index tailored to patients exposed to multidrug antiretroviral therapies and protease inhibitors, and to compare the new index to existing symptom measures. The research design was a multistage design including quantitative review of existing literature, qualitative and quantitative analyses of pilot data, and quantitative analyses of a prospective sample. Statistical analyses include frequencies, chi-square tests for significance, linear and logistic regression. The subjects were from a multisite convenience sample (n = 73) within the AIDS Clinical Trials Group and a prospective sample from the Cleveland Veterans Affairs Medical Center (n = 115). Measures were patient-reported symptoms and health-related quality of life, physician-assessed disease severity, CD4 cell count, and HIV-1 RNA viral quantification. A 20-item, self-completed HIV symptom index was developed based upon prior reports of symptom frequency and bother and expert opinion. When compared with prior measures the index included more frequent and bothersome symptoms, yet was easier to use (self-report rather than provider interview). The index required less than 5 minutes to complete, achieved excellent completion rates, and was thought comprehensive and comprehensible in a convenience sample. It was further tested in a prospective sample of patients and demonstrated strong associations with physical and mental health summary scores and with disease severity. These associations were independent of CD4 cell count and HIV-1 RNA viral quantification. This 20-item HIV symptom index has demonstrated construct validity, and offers a simple and rational approach to measuring HIV symptoms for clinical management, patient-oriented research, and adverse drug reporting.

Patient- and provider-reported adherence: toward a clinically useful approach to measuring antiretroviral adherence.

We seek to develop a clinically useful measure of antiretroviral medication adherence. Because there is no gold standard for adherence, we will assess the clinical validity of patient- and provider-reported adherence by the strength of their expected associations with current viral load, depressive symptoms, alcohol and illicit drug use, and homelessness. The Veterans Aging Cohort 3 Site Study (VACS 3) is a multisite study of 881 patients at Cleveland, Houston, and Manhattan Veterans Affairs health care systems. Data was collected on adherence using patient report and provider assessment; depressive symptoms using the Center for Epidemiological Studies Depression (CESD) and provider assessment; alcohol use using the Alcohol Use Disorders Identification Test (AUDIT) and provider assessment; and homelessness using patient report only. Viral load was collected from electronic laboratory data. Although agreement between providers and patients about the patient's adherence was not better than chance (61%; weighted kappa =.07), both patient and provider-reported adherence were related to viral load (P <.001), current alcohol use (P <.01), current drug use (P <.01), and depressive symptoms (P <.001). Patient-reported adherence was also associated with homelessness (P <.05). In multivariate regression models, provider assessment of adherence demonstrated independent associations with viral load (P <.001), current alcohol use (P <.001), current drug use (P <.001), and depressive symptoms (P <.001) after adjustment for the patient's report of adherence (also significantly associated). The consistent and largely independent association between patient and provider reported adherence and a range of variables previously shown to be associated with adherence suggests that patient- and provider-reported adherence independently measure actual adherence. Future work will explore how patient- and provider-reported adherence might best be combined, and whether the measure may be further enhanced with pharmacy refill data.

Limited patient adherence to highly active antiretroviral therapy for HIV-1 infection in an observational cohort study.

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) for human immunodeficiency syndrome type 1 (HIV-1) infection is essential to sustain viral suppression and prevent drug resistance. We investigated adherence to HAART among patients in a clinical cohort study. METHODS: Patients receiving HAART had their plasma concentrations of protease inhibitors or nevirapine measured and completed a questionnaire on adherence. We determined the percentage of patients who reported taking all antiretroviral medication on time and according to dietary instructions in the past week. Drug exposure was compared between patients reporting deviation from their regimen and fully adherent patients. Among patients who received HAART for at least 24 weeks, we assessed the association between adherence and virologic outcome. RESULTS: A total of 224 of 261 eligible patients completed a questionnaire. Forty-seven percent reported taking all antiretroviral medication on time and according to dietary instructions. Patients who reported deviation from their regimen showed lower drug exposure compared with fully adherent patients (median concentration ratio, 0.81 vs 1.07; P =.001). Among those receiving HAART for at least 24 weeks, patients reporting deviation from their regimen were less likely to have plasma HIV-1 RNA levels below 500 copies/mL (adjusted odds ratio, 4.0; 95% confidence interval, 1.4-11.6) compared with fully adherent patients. CONCLUSIONS: Only half of the patients took all antiretroviral medication in accordance with time and dietary instructions in the preceding week. Deviation from the antiretroviral regimen was associated with decreased drug exposure and a decreased likelihood of having suppressed plasma HIV-1 RNA loads. Patient adherence should remain a prime concern in the management of HIV-1 infection.

Provider assessment of adherence to HIV antiretroviral therapy.

BACKGROUND: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. OBJECTIVE: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. DESIGN, SETTING, AND PARTICIPANTS: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). MEASUREMENTS: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. RESULTS: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. CONCLUSIONS: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Anger inhibition potentiates the association of high end-tidal CO2 with blood pressure in women.

OBJECTIVE: High resting end-tidal CO2 (PetCO2) has been shown to be an independent predictor of systolic blood pressure (SBP) in women, particularly older women. The study reported in this article investigated whether the tendency to experience, express, and/or suppress anger contributes to the association of PetCO2 and SBP in women and in men. METHODS: The Spielberger Anger Expression Inventory was administered to 403 healthy male and female participants in the Baltimore Longitudinal Study on Aging. Resting PetCO2 was obtained by means of a respiratory gas monitor, and resting blood pressure was obtained with an oscillometric device. The associations of resting PetCO2 and the anger scales with SBP and diastolic blood pressure (DBP) were investigated using multivariate regression analyses. RESULTS: PetCO2, as well as age and body mass index, was an independent predictor of SBP in women with low, but not high, trait anger and in women with low, but not high, anger-out. PetCO2 was not an independent predictor of SBP in men with either high or low anger. In addition, PetCO2 was not an independent predictor of DBP in either men or women. CONCLUSIONS: The results of this study indicate that inhibition of anger potentiates the relationship of high PetCO2 with SBP in women but not men. Additional studies are needed to determine the origins of the observed gender differences and the psychophysiological pathways by which high resting PetCO2 contributes to elevated resting blood pressure in women.

Association of high resting end tidal CO2 with carotid artery thickness in women, but not men.

BACKGROUND: A previous study found high resting end tidal CO2 (PetCO2) to be an independent determinant of systolic blood pressure in women, but not men. The present study investigates the association of PetCO2 with the common carotid artery intima-media thickness (IMT) and wall-to-lumen (W/L) ratio in a sample of normotensive men and women. DESIGN AND METHODS: Resting PetCO2 of 188 healthy volunteers, including 88 men and 100 women, in the Baltimore Longitudinal Study on Aging was monitored continuously for 25 min via a respiratory gas monitor. At another session, carotid artery IMT was determined via high-resolution B-mode carotid ultrasonography. The ratio of IMT to carotid artery diameter was calculated as W/L ratio. Resting blood pressure was determined oscillometrically every 5 min for 20 min during each session. RESULTS: Univariate associations of PetCO2 with systolic blood pressure (SBP) (P< 001), IMT (P< 001) and W/L ratio (P< 001) were significant in women, but not men. Multiple regression analyses showed that high resting PetCO2 was a predictor of SBP (P < 01), IMT (P< 01) and W/L ratio (P< 01) in women, independent of age, body mass index and SBP. For men, age (P < 001) and SBP (P < 01) were independent predictors of carotid IMT, while age (P< 001) was the only independent predictor of W/L ratio in men. CONCLUSIONS: This study indicates that PetCO2 can play a role in cardiovascular structure, as well as function, in women, and that the relationship is independent of the association of PetCO2 with blood pressure.

Patients' attitudes toward cost control bonuses for managed care physicians.

Physicians' cost containment incentives may create conflicts of interest. To understand how patients view these incentives, we interviewed 1,050 patients regarding a 10 percent cost control bonus and a combined cost control/quality bonus. Seventy-three percent said that the cost control bonus was a bad idea; 49 percent viewed the combined bonus more favorably than the cost control bonus; and 91 percent favored disclosure of bonuses. We conclude that patients find bonuses worrisome and favor their disclosure. A quality component reassures some, but not all, patients. Initiating a dialogue with patients about practicing medicine in an era of limited resources may help health plans and physicians to address patients' concerns.

Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study.

The feasibility of providing postexposure prophylaxis (PEP) after sexual or injection drug use exposures to human immunodeficiency virus (HIV) was evaluated. PEP was provided within 72 h to individuals with exposures from partners known to have or to be at risk for HIV infection. PEP consisted of 4 weeks of antiretroviral medications and individually tailored risk-reduction and medication-adherence counseling. Among 401 participants seeking PEP, sexual exposures were most common (94%; n=375). Among sexual exposures, receptive (40%) and insertive (27%) anal intercourse were the most common sexual acts. The median time from exposure to treatment was 33 h. Ninety-seven percent of participants were treated exclusively with dual reverse-transcriptase inhibitors, and 78% completed the 4-week treatment. Six months after the exposure, no participant developed HIV antibodies, although a second PEP course for a subsequent exposure was provided to 12%. PEP, after nonoccupational HIV exposure, is feasible for persons at risk for HIV infection.

Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States.

BufferGel (ReProtect, LLC) is a vaginal gel with an acidic buffering action that was designed to prevent vaginal neutralization by semen. The purpose of this study was to evaluate the safety and tolerability of BufferGel (ReProtect, Limited Liability Company) applied vaginally either once or twice daily by 27 women who were at low risk for acquisition of human immunodeficiency virus (HIV). Participants initially used the product once daily for 14 days and then twice daily for 14 days; they underwent colposcopy before and after product exposure. BufferGel was well tolerated, although two-thirds of the participants reported at least 1 mild or moderate adverse experience. The most common adverse events were irritative genitourinary symptoms. Product use was discontinued after 3 adverse events. BufferGel was well tolerated in women at low risk for acquisition of HIV; toxicity was limited and occurred at frequencies similar to those in women who did not use any vaginal product and at levels lower than in women who used detergent-based microbicides.

Dilemmas of self in the method.

In this article, the author focuses on the researcher in research. Challenged by the theory and criticism of self-indulgence, the author has, as the researcher, come out through reflection and self-scrutiny to address some of the dilemmas the research process has held for her. Dilemmas concerning interviewing women from Pakistan using interpreters have been covered previously. The dilemmas discussed in this article concern the position of the researcher and honesty, the criticism of Western dominance, and how the research process has changed the author.

Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection.

Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes.