Perceived acceptability of home-based couples voluntary HIV counseling and testing in Northern Tanzania.

It is estimated that 5.6% of the Tanzanian population ages 15-49 are infected with HIV, but only 30% of adults have ever had an HIV test. Couples' testing has proven to increase testing coverage and introduce HIV prevention, but barriers include access to testing services and unequal gender dynamics in relationships. Innovative approaches are needed to address barriers to couple's testing and increase uptake of HIV testing. Using qualitative data collection methods, a formative study was conducted to assess the acceptability of a home-based couples counseling and testing (HBCCT) approach. Eligible study participants included married men and women, HIV-infected individuals, health care and home-based care providers, voluntary counseling and testing counselors, and community leaders. A total of 91 individuals participated in focus group discussions (FGDs) and in-depth interviews conducted between September 2009 and January 2010 in rural settings in Northern Tanzania. An HBCCT intervention appears to be broadly acceptable among participants. Benefits of HBCCT were identified in terms of access, confidentiality, and strengthening the relationship. Fears of negative consequences from knowing one's HIV status, including stigma, blame, physical abuse, or divorce, remain a concern and a potential barrier to the successful provision of the intervention. Lessons for implementation highlighted the importance of appointments for home visits, building relationships of confidence and trust between counselors and clients, and assessing and responding to a couple's readiness to undergo HIV testing. HBCCT should addresses HIV stigma, emphasize confidentiality, and improve communication skills for disclosure and decision-making among couples.

Optimized approach to decision fusion of heterogeneous data for breast cancer diagnosis.

As more diagnostic testing options become available to physicians, it becomes more difficult to combine various types of medical information together in order to optimize the overall diagnosis. To improve diagnostic performance, here we introduce an approach to optimize a decision-fusion technique to combine heterogeneous information, such as from different modalities, feature categories, or institutions. For classifier comparison we used two performance metrics: The receiving operator characteristic (ROC) area under the curve [area under the ROC curve (AUC)] and the normalized partial area under the curve (pAUC). This study used four classifiers: Linear discriminant analysis (LDA), artificial neural network (ANN), and two variants of our decision-fusion technique, AUC-optimized (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these classifiers with 100-fold cross-validation to two heterogeneous breast cancer data sets: One of mass lesion features and a much more challenging one of microcalcification lesion features. For the calcification data set, DF-A outperformed the other classifiers in terms of AUC (p < 0.02) and achieved AUC=0.85 +/- 0.01. The DF-P surpassed the other classifiers in terms of pAUC (p < 0.01) and reached pAUC=0.38 +/- 0.02. For the mass data set, DF-A outperformed both the ANN and the LDA (p < 0.04) and achieved AUC=0.94 +/- 0.01. Although for this data set there were no statistically significant differences among the classifiers' pAUC values (pAUC=0.57 +/- 0.07 to 0.67 +/- 0.05, p > 0.10), the DF-P did significantly improve specificity versus the LDA at both 98% and 100% sensitivity (p < 0.04). In conclusion, decision fusion directly optimized clinically significant performance measures, such as AUC and pAUC, and sometimes outperformed two well-known machine-learning techniques when applied to two different breast cancer data sets.

Pairing QuantiFERON gold in-tube with opt-out HIV testing in a tuberculosis contact investigation in the Southeastern United States.

Knowing one's HIV status is particularly important in the setting of recent tuberculosis (TB) exposure. Blood tests for assessment of tuberculosis infection, such as the QuantiFERON Gold in-tube test (QFT; Cellestis Limited, Carnegie, Victoria, Australia), offer the possibility of simultaneous screening for TB and HIV with a single blood draw. We performed a cross-sectional analysis of all contacts to a highly infectious TB case in a large meatpacking factory. Twenty-two percent were foreign-born and 73% were black. Contacts were tested with both tuberculin skin testing (TST) and QFT. HIV testing was offered on an opt-out basis. Persons with TST >or=10 mm, positive QFT, and/or positive HIV test were offered latent TB treatment. Three hundred twenty-six contacts were screened: TST results were available for 266 people and an additional 24 reported a prior positive TST for a total of 290 persons with any TST result (89.0%). Adequate QFT specimens were obtained for 312 (95.7%) of persons. Thirty-two persons had QFT results but did not return for TST reading. Twenty-two percent met the criteria for latent TB infection. Eighty-eight percent accepted HIV testing. Two (0.7%) were HIV seropositive; both individuals were already aware of their HIV status, but one had stopped care a year previously. None of the HIV-seropositive persons had latent TB, but all were offered latent TB treatment per standard guidelines. This demonstrates that opt-out HIV testing combined with QFT in a large TB contact investigation was feasible and useful. HIV testing was also widely accepted. Pairing QFT with opt-out HIV testing should be strongly considered when possible.

Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania.

BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.

Correlates of HIV testing among abused women in South Africa.

Gender-based violence increases a woman's risk for HIV but little is known about her decision to get tested. We interviewed 97 women seeking abuse-related services from a nongovernmental organization (NGO) in Johannesburg, South Africa. Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing. Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing. Providing safe access to integrated services and testing may increase testing in this population. Infection with HIV is highly prevalent in South Africa where an estimated 16.2% of adults between the ages of 15 and 49 have the virus. The necessary first step to stemming the spread of HIV and receiving life-saving treatment is learning one's HIV serostatus through testing. Many factors may contribute to someone's risk of HIV infection and many barriers may prevent testing. One factor that does both is gender-based violence.

HIV/AIDS-related institutional mistrust among multiethnic men who have sex with men: effects on HIV testing and risk behaviors.

OBJECTIVE: To investigate relationships between institutional mistrust (systematic discrimination, organizational suspicion, and conspiracy beliefs), HIV risk behaviors, and HIV testing in a multiethnic sample of men who have sex with men (MSM), and to test whether perceived susceptibility to HIV mediates these relationships for White and ethnic minority MSM. METHOD: Participants were 394 MSM residing in Central Arizona (M age = 37 years). Three dimensions of mistrust were examined, including organizational suspicion, conspiracy beliefs, and systematic discrimination. Assessments of sexual risk behavior, HIV testing, and perceived susceptibility to HIV were made at study entry (T1) and again 6 months later (T2). RESULTS: There were no main effects of institutional mistrust dimensions or ethnic minority status on T2 risk behavior, but the interaction of systematic discrimination and conspiracy beliefs with minority status was significant such that higher levels of systematic discrimination and more conspiracy beliefs were associated with increased risk only among ethnic minority MSM. Higher levels of systematic discrimination were significantly related to lower likelihood for HIV testing, and the interaction of organizational suspicion with minority status was significant such that greater levels of organizational suspicion were related to less likelihood of having been tested for HIV among ethnic minority MSM. Perceived susceptibility did not mediate these relationships. CONCLUSION: Findings suggest that it is important to look further into the differential effects of institutional mistrust across marginalized groups, including sexual and ethnic minorities. Aspects of mistrust should be addressed in HIV prevention and counseling efforts.

Economics of new oncology drug development.

PURPOSE: Review existing studies and provide new results on the development, regulatory, and market aspects of new oncology drug development. METHODS: We utilized data from the US Food and Drug Administration (FDA), company surveys, and publicly available commercial business intelligence databases on new oncology drugs approved in the United States and on investigational oncology drugs to estimate average development and regulatory approval times, clinical approval success rates, first-in-class status, and global market diffusion. RESULTS: We found that approved new oncology drugs to have a disproportionately high share of FDA priority review ratings, of orphan drug designations at approval, and of drugs that were granted inclusion in at least one of the FDA's expedited access programs. US regulatory approval times were shorter, on average, for oncology drugs (0.5 years), but US clinical development times were longer on average (1.5 years). Clinical approval success rates were similar for oncology and other drugs, but proportionately more of the oncology failures reached expensive late-stage clinical testing before being abandoned. In relation to other drugs, new oncology drug approvals were more often first-in-class and diffused more widely across important international markets. CONCLUSION: The market success of oncology drugs has induced a substantial amount of investment in oncology drug development in the last decade or so. However, given the great need for further progress, the extent to which efforts to develop new oncology drugs will grow depends on future public-sector investment in basic research, developments in translational medicine, and regulatory reforms that advance drug-development science.

An active learning approach for rapid characterization of endothelial cells in human tumors.

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

Cardiorespiratory fitness and cognitive function in midlife: neuroprotection or neuroselection?

OBJECTIVE: A study was undertaken to determine whether better cognitive functioning at midlife among more physically fit individuals reflects neuroprotection, by which fitness protects against age-related cognitive decline, or neuroselection, by which children with higher cognitive functioning select more active lifestyles. METHODS: Children in the Dunedin Longitudinal Study (N = 1,037) completed the Wechsler Intelligence Scales and the Trail Making, Rey Delayed Recall, and Grooved Pegboard tasks as children and again at midlife (age = 38 years). Adult cardiorespiratory fitness was assessed using a submaximal exercise test to estimate maximum oxygen consumption adjusted for body weight in milliliters/minute/kilogram. We tested whether more fit individuals had better cognitive functioning than their less fit counterparts (which could be consistent with neuroprotection), and whether better childhood cognitive functioning predisposed to better adult cardiorespiratory fitness (neuroselection). Finally, we examined possible mechanisms of neuroselection. RESULTS: Participants with better cardiorespiratory fitness had higher cognitive test scores at midlife. However, fitness-associated advantages in cognitive functioning were already present in childhood. After accounting for childhood baseline performance on the same cognitive tests, there was no association between cardiorespiratory fitness and midlife cognitive functioning. Socioeconomic and health advantages in childhood and healthier lifestyles during young adulthood explained most of the association between childhood cognitive functioning and adult cardiorespiratory fitness. INTERPRETATION: We found no evidence for a neuroprotective effect of cardiorespiratory fitness as of midlife. Instead, children with better cognitive functioning are selecting healthier lives. Fitness interventions may enhance cognitive functioning. However, observational and experimental studies testing neuroprotective effects of physical fitness should consider confounding by neuroselection.

Development and usability testing of a Web-based decision aid for families of patients receiving prolonged mechanical ventilation.

BACKGROUND: Web-based decision aids are increasingly important in medical research and clinical care. However, few have been studied in an intensive care unit setting. The objectives of this study were to develop a Web-based decision aid for family members of patients receiving prolonged mechanical ventilation and to evaluate its usability and acceptability. METHODS: Using an iterative process involving 48 critical illness survivors, family surrogate decision makers, and intensivists, we developed a Web-based decision aid addressing goals of care preferences for surrogate decision makers of patients with prolonged mechanical ventilation that could be either administered by study staff or completed independently by family members (Development Phase). After piloting the decision aid among 13 surrogate decision makers and seven intensivists, we assessed the decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate decision makers using the Systems Usability Scale (SUS). Acceptability was assessed using measures of satisfaction and preference for electronic Collaborative Decision Support (eCODES) versus the original printed decision aid. RESULTS: The final decision aid, termed 'electronic Collaborative Decision Support', provides a framework for shared decision making, elicits relevant values and preferences, incorporates clinical data to personalize prognostic estimates generated from the ProVent prediction model, generates a printable document summarizing the user's interaction with the decision aid, and can digitally archive each user session. Usability was excellent (mean SUS, 80 ± 10) overall, but lower among those 56 years and older (73 ± 7) versus those who were younger (84 ± 9); p = 0.03. A total of 93% of users reported a preference for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid for ICU surrogate decision makers can facilitate highly individualized information sharing with excellent usability and acceptability. Decision aids that employ an electronic format such as eCODES represent a strategy that could enhance patient-clinician collaboration and decision making quality in intensive care.

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration.

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ(2) test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.