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Sample records for hiv-related clinical endpoints

  1. Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials

    DEFF Research Database (Denmark)

    Lifson, A; Rahme, FS; Belloso, WH

    2006-01-01

    PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression...

  2. Sample size determination in clinical trials with multiple endpoints

    CERN Document Server

    Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2015-01-01

    This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...

  3. The Asthma Control Questionnaire as a clinical trial endpoint

    DEFF Research Database (Denmark)

    Barnes, P J; Casale, T B; Dahl, Ronald

    2014-01-01

    these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly...

  4. Is Doubling of Serum Creatinine a Valid Clinical 'Hard' Endpoint in Clinical Nephrology Trials?

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; Perkovic, V.; de Zeeuw, D.

    2011-01-01

    The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large

  5. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Science.gov (United States)

    2010-04-01

    ... effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510 Food... a clinical endpoint other than survival or irreversible morbidity. FDA may grant marketing approval... an effect on a clinical endpoint other than survival or irreversible morbidity. Approval under this...

  6. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Science.gov (United States)

    2010-04-01

    ... effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... survival or irreversible morbidity. Approval under this section will be subject to the requirement that the...

  7. The impact of Highly Active Antiretroviral Therapy (HAART on the clinical features of HIV - related oral lesions in Nigeria

    Directory of Open Access Journals (Sweden)

    Hassan Zuwaira

    2010-06-01

    Full Text Available Abstract Background This study aimed to determine the therapeutic effects of highly active anti-retroviral therapy (HAART on the clinical presentations of HIV related oral lesions (HIV-ROLs in an adult Nigerian population. Methods A 5 month prospective study on HAART naïve HIV positive adults recruited into the HAART program of an AIDS referral centre. HIV-ROLs were diagnosed clinically by the EEC Clearinghouse on oral problems related to HIV infection. Baseline clinical features of HIV-ROLs was documented by clinical photographs using SONY® 5.2 M Cybershot digital camera. Post HAART monthly review was conducted using clinical photographs. Results A total of 142 patients were seen. Age range was 19 - 75 years. Mean age was 35.6 ± 10.5 (SD. Eighty (56.3% were females. Prevalence of HIV-ROLs was 43.7%. Oral candidiasis (22.4% was the most prevalent HIV-ROL. 114 (83.2% patients had clinical AIDS at presentation (CDC 1993. 89.4% were placed on Tenofovir/Emtricitabine +`Nevirapine, 9.9% on Tenofovir/Emtricitabine + Efavirenz. There was strong decline in the clinical features of oral candidiasis from a month of commencing HAART. Oral hairy leukoplakia was slow in responding to HAART. Parotid gland enlargement, melanotic hyperpigmentation and Kaposi's sarcoma were more persistent and had slower response to HAART. There was no clinical change noticed in linear gingival erythema. Conclusion HAART has different clinical effects on HIV related oral lesions depending on the size, duration of treatment and etiology of the lesions. HIV-ROLs of fungal origin have the fastest response to HAART. These lesions alongside immunologic parameters can be used as indicators of success or failure of antiretroviral therapy.

  8. Intra-Cluster Correlation Estimates for HIV-related Outcomes from Care and Treatment Clinics in Dar es Salaam, Tanzania.

    Science.gov (United States)

    Barnhart, Dale; Hertzmark, Ellen; Liu, Enju; Mungure, Ester; Muya, Aisa N; Sando, David; Chalamilla, Guerino; Ulenga, Nzovu; Bärnighausen, Till; Fawzi, Wafaie; Spiegelman, Donna

    2016-12-15

    Researchers planning cluster-randomized controlled trials (cRCTs) require estimates of the intra-cluster correlation coefficient (ICC) from previous studies for sample size calculations. This paper fills a persistent gap in the literature by providing estimates of ICCs for many key HIV-related clinical outcomes. Data from HIV-positive patients from 47 HIV care and treatment clinics in Dar es Salaam, Tanzania were used to calculate ICCs by site of enrollment or site of ART initiation for various clinical outcomes using cross-sectional and longitudinal data. ICCs were estimated using linear mixed models where either clinic of enrollment or clinic of ART initiation served as the random effect. ICCs ranged from 0 to 0.0706 (95% CI: 0.0447, 0.1098). For most outcomes, the ICCs were large enough to meaningfully affect sample size calculations. For binary outcomes, the ICCs for event prevalence at baseline tended to be larger than the ICCs for later cumulative incidences. For continuous outcomes, the ICCs for baseline values tended to be larger than the ICCs for the change in values from baseline. The ICCs for HIV-related outcomes cannot be ignored when calculating sample sizes for future cluster-randomized trials. The differences between ICCs calculated from baseline data alone and ICCs calculated using longitudinal data demonstrate the importance of selecting an ICC that reflects a study's intended design and duration for sample size calculations. While not generalizable to all contexts, these estimates provide guidance for future researchers seeking to design adequately powered cRCTs in Sub-Saharan African HIV treatment and care clinics.

  9. Patients’ preferences for selection of endpoints in cardiovascular clinical trials

    Directory of Open Access Journals (Sweden)

    Robert D. Chow

    2014-02-01

    Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but

  10. Clinical features and management of non-HIV related lipodystrophy in children: A systematic review

    Science.gov (United States)

    Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, Scopus and Non-Indexe...

  11. CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY.

    Science.gov (United States)

    Luna, Leonardo Duarte Sobreira; Soares, Douglas de Sousa; Junior, Geraldo Bezerra da Silva; Cavalcante, Malena Gadelha; Malveira, Lara Raissa Cavalcante; Meneses, Gdayllon Cavalcante; Pereira, Eanes Delgado Barros; Daher, Elizabeth De Francesco

    2016-07-11

    The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death.

  12. Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

    Science.gov (United States)

    Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

    2015-06-25

    Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

  13. Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry : A Candidate Clinical Endpoint

    NARCIS (Netherlands)

    Zijlstra, Willemijn M H; Ploegstra, Mark-Jan; Vissia-Kazemier, Theresia R; Roofthooft, Marcus T. R.; du Marchie Sarvaas, Gideon; Bartelds, Beatrijs; Rackowitz, Annette; van den Heuvel, Freek; Hillege, Hans L; Plasqui, Guy; Berger, Rolf M F

    2017-01-01

    Rationale: The development of evidence-based treatment guidelines for pediatric pulmonary arterial hypertension (PAH) is hampered by lack of pediatric clinical trials. Trial design is hampered by lack of a feasible clinical endpoint in this population. Objectives: To evaluate the use of

  14. Systematic adjudication of myocardial infarction end-points in an international clinical trial.

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); K.M. Akkerhuis (Martijn)

    2001-01-01

    textabstractBACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected

  15. Systematic adjudication of myocardial infarction end-points in an international clinical trial

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); K.M. Akkerhuis (Martijn); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert)

    2001-01-01

    textabstractBackground. Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected

  16. Systematic adjudication of myocardial infarction end-points in an international clinical trial

    Directory of Open Access Journals (Sweden)

    Lee Kerry L

    2001-07-01

    Full Text Available Abstract Background Clinical events committees (CEC are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment myocardial infarction (MI in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide Therapy (PURSUIT trial. Methods The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. Results The CEC identified 5005 patients with suspected infarction (46%, of which 1415 (28% were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. Conclusions End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.

  17. [Patient-reported clinical trial endpoints--the current state of affairs in research and practice].

    Science.gov (United States)

    Kohlmann, Thomas

    2010-01-01

    Patient-reported outcomes are increasingly considered as endpoints for clinical studies. Instruments for measuring patient-reported outcomes range from simple assessments of discrete symptoms or signs to complex measures addressing multidimensional constructs such as health-related quality of life. While generic measures are designed to be applicable across a wide range of clinical conditions, disease- or population-specific instruments address health problems which are relevant for a particular disease or target group. Patient-reported outcomes can provide supplementary information from the patient's perspective when clinical endpoints are the primary focus of a study. As predictors and mediators of clinical outcomes they may contribute to the understanding of how patients benefit from treatment. They are included as primary endpoints when treatment effects comprise subjective phenomena such as pain, fatigue or psychological well-being. Current research activities in the field of patient-reported outcomes include the development of new (disease-specific) instruments, head-to-head comparisons of psychometric properties of measures, analysis of the context-dependence of results, and application of patient-reported outcomes in clinical practice.

  18. Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

    Science.gov (United States)

    Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

    2013-01-01

    Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials.

    Science.gov (United States)

    Kaufman, Howard L; Andtbacka, Robert H I; Collichio, Frances A; Wolf, Michael; Zhao, Zhongyun; Shilkrut, Mark; Puzanov, Igor; Ross, Merrick

    2017-09-19

    Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival. We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an oncolytic virus for melanoma treatment. To evaluate the association between DRR and OS and to mitigate lead time bias, landmark analyses were used. QoL was evaluated using the FACT-BRM questionnaire (comprising the FACT-BRM Physical, Social/Family, Emotional, and Functional well-being domains, the Additional Concerns, Physical and Mental treatment-specific subscales, and the Trial Outcome Index [TOI]). TFI was defined as time from the last study therapy dose to first subsequent therapy dose (including any systemic anticancer therapy for melanoma after study therapy discontinuation). Four hundred thirty-six patients were included in the intent-to-treat population. Achieving DR was associated with a statistically significant improvement in OS in a landmark analysis at 9 months (HR = 0.07; P = 0.0003), 12 months (HR = 0.05, P < 0.0001), and 18 months (HR = 0.11; P = 0.0002) that persisted after adjusting for disease stage and line of therapy. Achieving a DR was associated with a longer median TFI (HR = 0.33; P = 0.0007) and a higher TOI improvement rate (58.1% versus 30.0%; P = 0.025). Achieving a DR was associated with clinical benefits such as improved OS and QoL and prolonged TFI, thus supporting the usefulness of DR as a meaningful immunotherapy clinical trial

  20. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium.

    Science.gov (United States)

    Stone, Gregg W; Adams, David H; Abraham, William T; Kappetein, Arie Pieter; Généreux, Philippe; Vranckx, Pascal; Mehran, Roxana; Kuck, Karl-Heinz; Leon, Martin B; Piazza, Nicolo; Head, Stuart J; Filippatos, Gerasimos; Vahanian, Alec S

    2015-08-01

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Published on behalf of the European Society of Cardiology. All rights reserved. © American College of Cardiology

  1. HIV-related diarrhoea.

    Science.gov (United States)

    Kelly, P

    1998-02-01

    Common causes of persistent diarrhea, diarrhea which lasts for more than 2 weeks, in developing countries include infection with protozoans, bacteria, and viruses. The cause of HIV-related diarrhea varies from one area to another. Persistent diarrhea is more common among people who have advanced HIV disease than among those who do not, and is a major problem for many people with HIV/AIDS. The main dangers of diarrhea are dehydration and malnutrition. People with HIV-related diarrhea can become malnourished and lose weight quickly, mainly because they do not eat well due to poor appetite. Moreover, since weight loss is associated with HIV infection, people with diarrhea may be assumed to have HIV, and be stigmatized. Good hygiene and nutrition are the best ways to prevent diarrhea. While drinking boiled water is recommended, it is often not practical. Washing hands frequently with soap is a more practical prevention strategy. Other prevention strategies include storing food under a cover; washing eating and cooking utensils; washing raw fruit and vegetables; disposing of waste properly; and keeping anything dirty, such as soiled bedding, out of the reach of children. Nutritious, readily digestible food is also needed to prevent and treat diarrhea. Treatment recommendations are offered, as well as a guide to eating well.

  2. Clinical outcome endpoints in heart failure trials : a European Society of Cardiology Heart Failure Association consensus document

    NARCIS (Netherlands)

    Zannad, Faiez; Garcia, Angeles Alonso; Anker, Stefan D.; Armstrong, Paul W.; Calvo, Gonzalo; Cleland, John G. F.; Cohn, Jay N.; Dickstein, Kenneth; Domanski, Michael J.; Ekman, Inger; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Hernandez, Adrian F.; Jaarsma, Tiny; Koglin, Joerg; Konstam, Marvin; Kupfer, Stuart; Maggioni, Aldo P.; Mebazaa, Alexandre; Metra, Marco; Nowack, Christina; Pieske, Burkert; Pina, Ileana L.; Pocock, Stuart J.; Ponikowski, Piotr; Rosano, Giuseppe; Ruilope, Luis M.; Ruschitzka, Frank; Severin, Thomas; Solomon, Scott; Stein, Kenneth; Stockbridge, Norman L.; Stough, Wendy Gattis; Swedberg, Karl; Tavazzi, Luigi; Voors, Adriaan A.; Wasserman, ScottM.; Woehrle, Holger; Zalewski, Andrew; McMurray, John J. V.

    2013-01-01

    Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials

  3. Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients.

    Science.gov (United States)

    Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi

    2013-01-01

    Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

  4. Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials

    Directory of Open Access Journals (Sweden)

    Jessica S. Suwandi

    2017-11-01

    Full Text Available Tolerogenic dendritic cells (tolDCs have reached patients with autoimmune and inflammatory disease, at least in clinical trials. The safety of tolDCs as intervention therapy has been established, but the capacity to modulate autoimmune response in vivo remains to be demonstrated. Studies have revealed a diversity of regulatory mechanisms that tolDCs may employ in vivo. These mechanisms differ between various types of modulated tolDC. The most often foreseen action of tolDCs is through regulatory polarization of naïve T cells or activation of existing regulatory T cells, which should ultimately diminish autoimmune inflammation. Yet, selection of a target autoantigen remains critical to expedite tissue specific tolerance induction, while measuring immune modulation incited by tolDCs in vivo provides a great challenge. We will discuss the regulatory action of different types of tolDCs and the possible methods to monitor immunological efficacy endpoints for the next generation clinical trials.

  5. Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical trials with ultrasound endpoints.

    Science.gov (United States)

    Allen, John C; Thumboo, Julian; Lye, Weng Kit; Conaghan, Philip G; Chew, Li-Ching; Tan, York Kiat

    2017-10-03

    To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H0 : ES = 0 versus alternative hypotheses H1 : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  6. Efficient confidence limits for adaptive one-arm two-stage clinical trials with binary endpoints

    Directory of Open Access Journals (Sweden)

    Guogen Shan

    2017-02-01

    Full Text Available Abstract Background Recently, several adaptive one-arm two-stage designs have been developed by fully using the information from previous stages to reduce the expected sample size in clinical trials with binary endpoints as primary outcome. It is important to compute exact confidence limits for these studies. Methods In this article, we propose three new one-sided limits by ordering the sample space based on p-value, average response rate at each stage, and asymptotic lower limit, as compared to another three existing sample size ordering approaches based on average response rate. Among the three proposed approaches, the one based on the average response rate at each stage is not exact, and the remaining two approaches are exact with the coverage probability guaranteed. Results We compare these exact intervals by using the two commonly used criteria: simple average length and expected length. The existing three approaches based on average response rate have similar performance, and they have shorter expected lengths than the two proposed exact approaches although the gain is small, while this trend is reversed under the simple average criterion. Conclusions We would recommend the two exact proposed approaches based on p-value and asymptotic lower limit under the simple average length criterion, and the approach based on average response rate under the expected length criterion.

  7. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Hoskin, Peter [Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Mitera, Gunita; Zeng Liang [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Lutz, Stephen [Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, OH (United States); Roos, Daniel [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Linden, Yvette van der [Radiotherapeutic Institute Friesland, Leeuwarden (Netherlands); Hartsell, William [Department of Radiation Oncology, Advocate Good Samaritan Cancer Center, Downers Grove, IL (United States); Kumar, Eshwar [Department of Oncology, Atlantic Health Sciences Cancer Centre, Saint John Regional Hospital, Saint John, NB (Canada)

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  8. Planning and evaluating clinical trials with composite time-to-first-event endpoints in a competing risk framework.

    Science.gov (United States)

    Rauch, G; Beyersmann, J

    2013-09-20

    Composite endpoints combine several events of interest within a single variable. These are often time-to-first-event data, which are analyzed via survival analysis techniques. To demonstrate the significance of an overall clinical benefit, it is sufficient to assess the test problem formulated for the composite. However, the effect observed for the composite does not necessarily reflect the effects for the components. Therefore, it would be desirable that the sample size for clinical trials using composite endpoints provides enough power not only to detect a clinically relevant superiority for the composite but also to address the components in an adequate way. The single components of a composite endpoint assessed as time-to-first-event define competing risks. We consider multiple test problems based on the cause-specific hazards of competing events to address the problem of analyzing both a composite endpoint and its components. Thereby, we use sequentially rejective test procedures to reduce the power loss to a minimum. We show how to calculate the sample size for the given multiple test problem by using a simply applicable simulation tool in SAS. Our ideas are illustrated by two clinical study examples. Copyright © 2013 John Wiley & Sons, Ltd.

  9. The feasibility of clinical endpoint trials in HIV infection in the highly active antiretroviral treatment (HAART) era

    DEFF Research Database (Denmark)

    Mocroft, A; Neaton, J; Bebchuk, J

    2006-01-01

    the assumptions used in designing ESPRIT, a large randomized clinical trial assessing the clinical benefit of interleukin-2 treatment in patients with HIV infection, to use EuroSIDA to mimic the inclusion criterion of ESPRIT in order to compare the observed event rate in ESPRIT with the projected rate in Euro......BACKGROUND: Planning clinical-endpoint trials in patients with HIV remain difficult as long-term follow-up of many patients is required. Cohort studies of patients with HIV can provide key estimates of the likely disease progression, required sample size and follow-up. OBJECTIVES: To verify...... to observational studies or clinical trials cannot always be adjusted for. CONCLUSIONS: Event rates in EuroSIDA were similar in the first two years to those used in the design of ESPRIT, but did not increase over time, leading to an increase in the expected duration of ESPRIT. Clinical endpoint trials in HIV...

  10. Sample size determination in group-sequential clinical trials with two co-primary endpoints

    Science.gov (United States)

    Asakura, Koko; Hamasaki, Toshimitsu; Sugimoto, Tomoyuki; Hayashi, Kenichi; Evans, Scott R; Sozu, Takashi

    2014-01-01

    We discuss sample size determination in group-sequential designs with two endpoints as co-primary. We derive the power and sample size within two decision-making frameworks. One is to claim the test intervention’s benefit relative to control when superiority is achieved for the two endpoints at the same interim timepoint of the trial. The other is when the superiority is achieved for the two endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the behaviors of sample size and power with varying design elements and provide a real example to illustrate the proposed sample size methods. In addition, we discuss sample size recalculation based on observed data and evaluate the impact on the power and Type I error rate. PMID:24676799

  11. Clinical adequacy assessment of autocontours for prostate IMRT with meaningful endpoints.

    Science.gov (United States)

    Nourzadeh, Hamidreza; Watkins, William T; Ahmed, Mahmoud; Hui, Cheukkai; Schlesinger, David; Siebers, Jeffrey V

    2017-04-01

    To determine if radiation treatment plans created based on autosegmented (AS) regions-of-interest (ROI)s are clinically equivalent to plans created based on manually segmented ROIs, where equivalence is evaluated using probabilistic dosimetric metrics and probabilistic biological endpoints for prostate IMRT. Manually drawn contours and autosegmented ROIs were created for 167 CT image sets acquired from 19 prostate patients. Autosegmentation was performed utilizing Pinnacle's Smart Probabilistic Image Contouring Engine. For each CT set, 78 Gy/39 fraction 7-beam IMRT treatment plans with 1 cm CTV-to-PTV margins were created for each of the three contour scenarios; PMD using manually delineated (MD) ROIs, PAS using autosegmented ROIs, and PAM using autosegmented organ-at-risks (OAR)s and the manually drawn target. For each plan, 1000 virtual treatment simulations with different systematic errors for each simulation and a different random error for each fraction were performed. The statistical probability of achieving dose-volume metrics (coverage probability (CP)), expectation values for normal tissue complication probability (NTCP), and tumor control probability (TCP) metrics for all possible cross-evaluation pairs of ROI types and planning scenarios were reported. In evaluation scenarios, the root mean square loss (RMSL) and maximum absolute loss (MAL) of coverage probability of dose-volume objectives, E[TCP], and E[NTCP] were compared with respect to the base plan created and evaluated with manually drawn contours. Femoral head dose objectives were satisfied in all situations, as well as the maximum dose objectives for all ROIs. Bladder metrics were within the clinical coverage tolerances except D35Gy for the autosegmented plan evaluated with the manual contours. Dosimetric indices for CTV and rectum could be highly compromised when the definition of the ROIs switched from manually delineated to autosegmented. Seventy-two percent of CT image sets satisfied the

  12. Sample size determination for a specific region in multiregional clinical trials with multiple co-primary endpoints.

    Directory of Open Access Journals (Sweden)

    Wong-Shian Huang

    Full Text Available Recently, multi-regional clinical trials (MRCTs, which incorporate subjects from many countries/regions around the world under the same protocol, have been widely conducted by many global pharmaceutical companies. The objective of such trials is to accelerate the development process for a drug and shorten the drug's approval time in key markets. Several statistical methods have been purposed for the design and evaluation of MRCTs, as well as for assessing the consistency of treatment effects across all regions with one primary endpoint. However, in some therapeutic areas (e.g., Alzheimer's disease, the clinical efficacy of a new treatment may be characterized by a set of possibly correlated endpoints, known as multiple co-primary endpoints. In this paper, we focus on a specific region and establish three statistical criteria for evaluating consistency between the specific region and overall results in MRCTs with multiple co-primary endpoints. More specifically, two of those criteria are used to assess whether the treatment effect in the region of interest is as large as that of the other regions or of the regions overall, while the other criterion is used to assess the consistency of the treatment effect of the specific region achieving a pre-specified threshold. The sample size required for the region of interest can also be evaluated based on these three criteria.

  13. Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

    Science.gov (United States)

    Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

    2013-03-01

    In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Generalized optimal design for two-arm, randomized phase II clinical trials with endpoints from the exponential dispersion family.

    Science.gov (United States)

    Jiang, Wei; Mahnken, Jonathan D; He, Jianghua; Mayo, Matthew S

    2016-11-01

    For two-arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre-specified precision. Its applications on data from specific distribution families are discussed under multiple design considerations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Nonadherence is Associated with Lack of HIV-Related Knowledge

    DEFF Research Database (Denmark)

    Dyrehave, Charlotte; Rasmussen, Dlama Nggida; Hønge, Bo Langhoff

    2016-01-01

    BACKGROUND: Poor treatment adherence is a main barrier for effective antiretroviral therapy (ART) globally. HIV-related knowledge may affect understanding and utilization of HIV medical information, hence limited health literacy is a known barrier to treatment adherence. DESIGN AND METHODS: A cro...... effects, food insecurity, and simply forgetting. Lack of HIV-related knowledge about ART and HIV may be a barrier to nonadherence.......% skipped their medicine during weekends. The most frequent reasons for not taking medicine were simply forgetting, side effects, lack of food, and being too ill to attend the clinic. Nonadherent patients had a lower level of HIV-related knowledge. CONCLUSION: Main barriers for nonadherence were side...

  16. THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

    Science.gov (United States)

    McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

    2013-01-01

    Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

  17. The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study.

    Science.gov (United States)

    McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

    2013-09-01

    An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate-determined energy expenditure index, and other exploratory endpoints. The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Copyright © 2013 Wiley Periodicals, Inc.

  18. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

    Science.gov (United States)

    Zhou, Heng; Lee, J Jack; Yuan, Ying

    2017-09-20

    We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment

    NARCIS (Netherlands)

    de Glas, N. A.; Hamaker, M. E.; Kiderlen, M.; de Craen, A. J. M.; Mooijaart, S. P.; van de Velde, C. J. H.; van Munster, B. C.; Portielje, J. E. A.; Liefers, G. J.; Bastiaannet, E.

    2014-01-01

    With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of

  20. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials

    DEFF Research Database (Denmark)

    Bottomley, Andrew; Pe, Madeline; Sloan, Jeff

    2016-01-01

    Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are anal...... data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making.......Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures......-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes...

  1. Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

    Science.gov (United States)

    Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

    2018-02-07

    Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

  2. Cognitive endpoints as disease biomarkers: optimizing the congruency of preclinical models to the clinic.

    Science.gov (United States)

    Day, Mark; Balci, Fuat; Wan, Hong I; Fox, Gerard B; Rutkowski, J Lynn; Feuerstein, Giora

    2008-07-01

    Cognition is a complex set of processes, including attention, learning and memory, that refers to the capacity to encode, consolidate, store and retrieve recent and remotely stored fact (semantic) and experience-based (episodic) memory. The development of cognitive enhancers is of particular importance to society and the pharmaceutical industry, as cognitive dysfunctions are observed across a wide range of neuropsychiatric and neurodegenerative disorders; however, developing such therapeutics has proven difficult. There is poor congruency between the abundance of positive results observed in animal studies compared with clinical outcome. For example, from 1982 to 2002 there was a 6000% increase in studies on cognitive processing in rodents that had little or no impact on the outcome of phase II and III clinical trials. The effects of therapeutics on models of cognition that demonstrate the potential to improve preclinical-to-clinical congruency, focusing on attention, impulsivity and episodic memory, are summarized in this review. Changes in attention, impulsivity and episodic memory are tractable 'disease biomarkers' that correlate with the disease phenotypes that are potential therapeutic targets. In the context of the development of cognitive enhancing drugs, one of the major goals of translational medicine is to improve the congruency between preclinical models and clinical results. Improved translatability could improve discovery, validation and implementation of biomarkers to inform clinical outcome studies and decision making, and to establish proof-of-concept for efficacy and safety based on targeted mechanisms of action.

  3. Choosing the best endpoint

    DEFF Research Database (Denmark)

    Christensen, Erik

    2008-01-01

    guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint......, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations...

  4. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2017-10-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing...manuscript resulting from the work described in Aim 2 has been published in the journal European Urology, titled: “Effects of Cabozantinib on Pain...resulting from work described in Aim 3 has been published by the journal Cancer, titled: “Pain Palliation Measurement in Cancer Clinical Trials: The

  5. Development of World Health Organization (WHO recommendations for appropriate clinical trial endpoints for next-generation Human Papillomavirus (HPV vaccines

    Directory of Open Access Journals (Sweden)

    Malavika Prabhu

    2016-12-01

    Full Text Available The World Health Organization (WHO serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV vaccine as an example, we describe the process by which (1 a need to revise the guidelines was identified; (2 a group of stakeholders with complementary expertise and key questions were identified; (3 a scientific review was conducted; (4 consensus on revisions was achieved; (5 guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Keywords: HPV vaccine, WHO, Policy guidelines

  6. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study

    Directory of Open Access Journals (Sweden)

    Lee Kerry L

    2001-07-01

    Full Text Available Abstract Background Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide Therapy (PURSUIT trial and those adjudicated by a central clinical events committee (CEC to determine the reasons for differences in event rates. Methods The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. Results The CEC identified 5005 (46% suspected events, of which 1415 (28% were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20% of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. Conclusion CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials.

  7. An evaluation of methods for testing hypotheses relating to two endpoints in a single clinical trial.

    Science.gov (United States)

    Su, Ting-Li; Glimm, Ekkehard; Whitehead, John; Branson, Mike

    2012-01-01

    The issues and dangers involved in testing multiple hypotheses are well recognised within the pharmaceutical industry. In reporting clinical trials, strenuous efforts are taken to avoid the inflation of type I error, with procedures such as the Bonferroni adjustment and its many elaborations and refinements being widely employed. Typically, such methods are conservative. They tend to be accurate if the multiple test statistics involved are mutually independent and achieve less than the type I error rate specified if these statistics are positively correlated. An alternative approach is to estimate the correlations between the test statistics and to perform a test that is conditional on those estimates being the true correlations. In this paper, we begin by assuming that test statistics are normally distributed and that their correlations are known. Under these circumstances, we explore several approaches to multiple testing, adapt them so that type I error is preserved exactly and then compare their powers over a range of true parameter values. For simplicity, the explorations are confined to the bivariate case. Having described the relative strengths and weaknesses of the approaches under study, we use simulation to assess the accuracy of the approximate theory developed when the correlations are estimated from the study data rather than being known in advance and when data are binary so that test statistics are only approximately normally distributed. Copyright © 2012 John Wiley & Sons, Ltd.

  8. An adapted Clavien-Dindo scoring system in trauma as a clinically meaningful nonmortality endpoint.

    Science.gov (United States)

    Naumann, David N; Vincent, Laura E; Pearson, Nicola; Beaven, Alastair; Smith, Iain M; Smith, Kieran; Toman, Emma; Dorrance, Helen R; Porter, Keith; Wade, Charles E; Cotton, Bryan A; Holcomb, John B; Midwinter, Mark J

    2017-08-01

    There is no consensus on reporting nonmortality trauma complications in a graded manner. The Clavien-Dindo scale of complications was originally for elective surgery and requires adaptation to provide meaningful data for trauma patients. In particular, the original score does not account for those treated without surgery. We report an adapted Clavien-Dindo in trauma (ACDiT) scale and apply it to patients managed operatively and nonoperatively. A combined prospective and retrospective international multicenter observational study was undertaken to apply the ACDiT scale to 484 trauma patients at three university teaching hospitals (Birmingham, England (n = 303); Houston, Texas (n = 113); and Glasgow, Scotland (n = 68)). These included both intensive care unit (ICU) and non-ICU-managed patients. The Clavien-Dindo scoring system was adapted for trauma patients based on consensus amongst an international collaboration of trauma specialists at these sites. Data included whether initial patients were managed operatively or nonoperatively. Complication grades were compared with hospital-free and ICU-free days as other outcome measures of patient morbidity. Two hundred seventeen (44.8%) of 484 patients experienced complications, of whom 61 (28.1%) of 217 died (grade V). The remainder consisted of grades I (n = 20), II (n = 60), III (n = 24), and IV (n = 52). There was a strong association between higher ACDiT grade category and lower number of hospital-free and ICU-free days (p < 0.01). Eighty-eight patients with complications did not require surgery, validating the score's usefulness in patients managed nonoperatively. The ACDiT scale can be used to grade the severity of posttrauma complications in patients managed both operatively and nonoperatively. It provides clinically meaningful data for morbidity and mortality meetings and other quality improvement exercises. Prognostic, level IV.

  9. 76 FR 35450 - Draft Guidance for Industry on Clinical Trial Endpoints for the Approval of Non-Small Cell Lung...

    Science.gov (United States)

    2011-06-17

    ... Cancer Drugs and Biologics.'' FDA is developing guidance on oncology endpoints through a process that... Endpoints for the Approval of Cancer Drugs and Biologics;'' \\1\\ it is the first in a series of oncology... the Approval of Non-Small Cell Lung Cancer Drugs and Biologics; Availability AGENCY: Food and Drug...

  10. Maximum predictive power of the microarray-based models for clinical outcomes is limited by correlation between endpoint and gene expression profile.

    Science.gov (United States)

    Zhao, Chen; Shi, Leming; Tong, Weida; Shaughnessy, John D; Oberthuer, André; Pusztai, Lajos; Deng, Youping; Symmans, W Fraser; Shi, Tieliu

    2011-12-23

    Microarray data have been used for gene signature selection to predict clinical outcomes. Many studies have attempted to identify factors that affect models' performance with only little success. Fine-tuning of model parameters and optimizing each step of the modeling process often results in over-fitting problems without improving performance. We propose a quantitative measurement, termed consistency degree, to detect the correlation between disease endpoint and gene expression profile. Different endpoints were shown to have different consistency degrees to gene expression profiles. The validity of this measurement to estimate the consistency was tested with significance at a p-value less than 2.2e-16 for all of the studied endpoints. According to the consistency degree score, overall survival milestone outcome of multiple myeloma was proposed to extend from 730 days to 1561 days, which is more consistent with gene expression profile. For various clinical endpoints, the maximum predictive powers of different microarray-based models are limited by the correlation between endpoint and gene expression profile of disease samples as indicated by the consistency degree score. In addition, previous defined clinical outcomes can also be reassessed and refined more coherent according to related disease gene expression profile. Our findings point to an entirely new direction for assessing the microarray-based predictive models and provide important information to gene signature based clinical applications.

  11. HIV related renal disease in Africans | Elangovan | IMTU Medical ...

    African Journals Online (AJOL)

    Renal disease is becoming an increasingly prevalent entity in human immunodefi ciency virus (HIV)–infected patients, first diagnosed in AIDS patients in 1984. The HIV-related renal disease represents a spectrum of clinical and histological conditions presenting as acute renal failure, chronic renal failure, glomerulopathies, ...

  12. Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda MD)

    Science.gov (United States)

    Helfer, Jennifer L.; Wen, Patrick Y.; Blakeley, Jaishri; Gilbert, Mark R.; Armstrong, Terri S.

    2016-01-01

    On October 15, 2014, a workshop was held on the use of clinical outcome assessments in clinical trials for high-grade glioma of the brain. This workshop was sponsored by the Jumpstarting Brain Tumor Drug Development Coalition, consisting of the National Brain Tumor Society, the Society for Neuro-Oncology, the Musella Foundation for Brain Tumor Research and Information, and Accelerate Brain Cancer Cure. It was planned and carried out with participation from the US Food and Drug Administration. The workshop also included stakeholders from all aspects of the brain tumor community, including clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and the National Cancer Institute. This report summarizes the presentations and discussions of that workshop and the proposals that emerged to move the field forward and toward greater inclusion of these endpoints in future clinical trials for high-grade gliomas. PMID:26989130

  13. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    Science.gov (United States)

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  14. Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions: A Consensus Document From the Mitral Valve Academic Research Consortium.

    Science.gov (United States)

    Stone, Gregg W; Adams, David H; Abraham, William T; Kappetein, Arie Pieter; Généreux, Philippe; Vranckx, Pascal; Mehran, Roxana; Kuck, Karl-Heinz; Leon, Martin B; Piazza, Nicolo; Head, Stuart J; Filippatos, Gerasimos; Vahanian, Alec S

    2015-07-21

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

    Science.gov (United States)

    Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

    2017-10-01

    Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

  16. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

    Science.gov (United States)

    Erdman, Laura K.; D’Acremont, Valérie; Hayford, Kyla; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Alamo, Leonor; Streiner, David L.; Genton, Blaise; Kain, Kevin C.

    2015-01-01

    Background Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. Methods We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. Results Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7

  17. Evaluation of the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite as clinical endpoints in multiple sclerosis clinical trials: quantitative meta-analyses.

    Science.gov (United States)

    Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

    2016-12-01

    This study compared the sensitivity of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) as clinical endpoints in multiple sclerosis (MS) clinical trials. Medline (1946 through 12 September 2014) and Embase (1974 through 12 September 2014) databases searches were conducted using keywords and Medical Subject Heading (MeSH) terms related to MS, EDSS, and MSFC. Only studies that used the EDSS and MSFC as endpoints were assessed. All statistical analyses were conducted using comprehensive meta-analysis (CMA). The percentages of the overall changes in EDSS and MSFC were compared. The relative risks were calculated in randomized clinical trials (RCTs). A total of 123 studies were identified. There were nine studies (6 case series and 3 RCTs) included in the analysis. In the case series, the EDSS change rate in MS patients was 33.5% (95% CI: 12.9-63.2%) and the MSFC change rate was 30.3% (95% CI: 9.2-65.2%). In RCTs, patients who take the drug would be 22.9 times as likely as patients who did not take the drug to experience a change in the EDSS scale (RR = 22.9, 95% CI = 0.996-1.517, p = 0.055). Patients who take the drug would be 48.9 times as likely as patients who did not take the drug to experience a change in the MSFC scale (RR = 48.9, 95% CI = CI = 0.916-2.419, p = 0.108). This study focused only on MS patient improvement (positive changes) on the EDSS and MSFC. More studies are needed to include patient deterioration (negative changes) on EDSS and MSFC. There is controversy about the sensitivity of the EDSS and MSFC in detecting the progression of MS disease. The EDSS and MSFC are effective tools to assess the clinical severity and progression of MS disease. MSFC is more sensitive than EDSS in detecting the progression of MS disease.

  18. Approaches to interim analysis of cancer randomised clinical trials with time to event endpoints: A survey from the Italian National Monitoring Centre for Clinical Trials

    Directory of Open Access Journals (Sweden)

    De Rosa Marisa

    2008-07-01

    Full Text Available Abstract Background Although interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials. Methods Source of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS or progression free survival (PFS. A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a general characteristics of the protocol b disease localization and patient setting; c study design d interim analyses; e DSMC. Results The analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols, and the planning of interim analysis, without DSMC (14.7%. Conclusion The results indicate that there is still insufficient attention paid to the implementation of interim analysis.

  19. HIV-related ocular microangiopathic syndrome and cognitive functioning.

    Science.gov (United States)

    Geier, S A; Perro, C; Klauss, V; Naber, D; Kronawitter, U; Bogner, J R; Goebel, F D; Lund, O E; Hippius, H

    1993-03-01

    Ocular microangiopathic syndrome is found frequently in patients with AIDS or severe HIV infection. Symptoms of this microvascular syndrome can include cotton-wool spots, hemorrhages, and Roth's spots. The clinical and functional significance of HIV-related ocular microangiopathic syndrome has not been clarified as yet. The objective of this study was to evaluate a possible association between HIV-related ocular microangiopathic syndrome and cognitive functioning. Thirty-seven patients infected with HIV (24 with AIDS) underwent ophthalmological and neuropsychological examination. HIV-related ocular microangiopathic syndrome was measured by counting the number of cotton-wool spots in both eyes. Neuropsychological examination included five standardized tests, with the first three primarily measuring function of short-term memory; these tests were as follows: the Auditory-Verbal Learning Test, the Benton Test, the Stroop Colour Word Test, the Trail-Making Part B test, and the Vocabulary for Measuring Premorbid Intelligence test. HIV-related ocular microangiopathic syndrome was found in 15 patients with AIDS (62.5%), and in one patient, staged Walter Reed 5. In 10 patients, one eye was affected (mean count of cotton-wool spots 1.5). In six patients, both eyes were affected (mean count of cotton-wool spots 7.0). Univariate correlations between the number of cotton-wool spots in both eyes and test scores were as follows: Auditory-Verbal Learning Test: 0.56 (p < 0.001); Benton Test: 0.51 (p < 0.001); Stroop Colour and Word: 0.50 (p < 0.001); Trail-Making Part B: 0.15 (not significant); Vocabulary for Measuring Premorbid Intelligence: -0.05 (not significant). Multiple correlation between the test scores and the number of cotton-wool spots was 0.70 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure.

    Science.gov (United States)

    Fonseca, Cândida; Maggioni, Aldo Pietro; Marques, Filipa; Araújo, Inês; Brás, Daniel; Langdon, Ronald B; Lombardi, Carlo; Bettencourt, Paulo

    2018-01-01

    In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set.

    Science.gov (United States)

    Ma, Christopher; Panaccione, Remo; Fedorak, Richard N; Parker, Claire E; Nguyen, Tran M; Khanna, Reena; Siegel, Corey A; Peyrin-Biroulet, Laurent; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Jairath, Vipul

    2017-08-24

    Advances in development of therapeutic agents for ulcerative colitis (UC) have been paralleled by innovations in trial design. It would be useful to identify a core outcome set, to standardize outcome definitions for efficacy and safety in clinical trials. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled randomized controlled trials of patients with UC. We searched MEDLINE, EMBASE, and the Cochrane Library from inception through March 1, 2017, for placebo-controlled randomized controlled trials of adult patients with UC treated with aminosalicylates, immunosuppressants, corticosteroids, biologics, and oral small molecules. We collected information on efficacy and safety outcomes, definitions, and measurement tools, stratified by decade of publication. We analyzed data from 83 randomized controlled trials (68 induction and 15 maintenance) comprising 17,737 patients. Clinical or composite-clinical efficacy outcomes were reported in all trials; the UC Disease Activity Index and Mayo Clinic Score were frequently used to determine clinical response or remission. We found substantial variation in definitions of clinical or composite-clinical endpoints, with more than 50 definitions of response or remission. Endoscopic factors, histologic features, and fecal or serum biomarkers were used to determine outcomes in 83.1% (69 of 83), 24.1% (20 of 83), and 24.1% (20 of 83) of trials, respectively. A greater proportion of trials published after 2007 reported objective outcomes (96.5% endoscopic, 26.3% histologic, and 36.8% biomarker outcomes), but no standardized definitions of histologic or biomarker endpoints were found. Patient-reported efficacy and quality-of-life outcomes were described in 25 trials (30.1%) and safety outcomes were reported in 77 trials (92.8%). In a systematic review, we found that despite recent advances in clinical trials methods, there is a great deal of variation in definitions of endpoints, including

  2. Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition

    DEFF Research Database (Denmark)

    Zannad, F.; Stough, W.G.; Pitt, B.

    2008-01-01

    Specific criteria have been established to define the occurrence of myocardial infarction (MI) and stroke in cardiovascular clinical trials, but there is not a consistent definition for heart failure. Heart failure events appear to occur at a rate that is similar to stroke and MI in trials...... of hypertension, hyperlipidaemia, diabetes, and coronary heart disease, yet a consistent approach to defining heart failure events has not yet been realized. The wide range of definitions used in clinical trials makes it difficult to interpret new data in the context of existing literature. This inconsistency has...... led to challenges in determining the incidence of heart failure in cardiovascular studies and the effects of interventions on these endpoints. This paper examines issues related to defining heart failure events in cardiovascular clinical trials and presents a definition to formally address this issue...

  3. Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

    Science.gov (United States)

    Shi, Haolun; Yin, Guosheng

    2018-02-21

    Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications. © 2018, The International Biometric Society.

  4. Inactivations, deletions, non-adjudications, and downgrades of clinical endpoints on ticagrelor: serious concerns over the reliability of the PLATO trial.

    Science.gov (United States)

    DiNicolantonio, James J; Tomek, Ales

    2013-10-09

    Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. We examined information from the FDA complete response review. FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p = 0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p = 0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR = 1.21, 95% CI: 0.91 to 1.59, p = 0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality. © 2013.

  5. The feasibility of clinical endpoint trials in HIV infection in the highly active antiretroviral treatment (HAART) era

    DEFF Research Database (Denmark)

    Mocroft, A; Neaton, J; Bebchuk, J

    2006-01-01

    the assumptions used in designing ESPRIT, a large randomized clinical trial assessing the clinical benefit of interleukin-2 treatment in patients with HIV infection, to use EuroSIDA to mimic the inclusion criterion of ESPRIT in order to compare the observed event rate in ESPRIT with the projected rate in Euro......SIDA, and to project the required length of ESPRIT. METHODS: Patients in EuroSIDA who satisfied the ESPRIT recruitment criteria were selected. Patients were followed from baseline to new AIDS or death. RESULTS: The incidence of clinical progression in the selected EuroSIDA patients (N = 4482) was 1.5 per 100 PYFU (95......% CI 1.3-1.7), and did not increase with increasing time from baseline, contrary to what was assumed in the design of the ESPRIT trial. In ESPRIT (N = 4150), for which the comparative data remain blinded, the incidence was 1.1 per 100 PYFU (95% CI 0.9-1.3), with no increase over time. The average...

  6. Percentage of subjects with no heavy drinking days: evaluation as an efficacy endpoint for alcohol clinical trials.

    Science.gov (United States)

    Falk, Daniel; Wang, Xin Qun; Liu, Lei; Fertig, Joanne; Mattson, Margaret; Ryan, Megan; Johnson, Bankole; Stout, Robert; Litten, Raye Z

    2010-12-01

    Percent subjects with no heavy drinking days (PSNHDDs), an efficacy end point recommended by the Food and Drug Administration, considers abstinent individuals or those engaging in low-risk drinking behavior as successful responders to treatment. As PSNHDD has been used infrequently in previous alcohol clinical trials, we evaluated the utility and validity of the PSNHDD outcome measure in 2 large alcohol clinical trials. Data sets from 2 alcohol trials, COMBINE and a multisite topiramate trial, were used to analyze PSNHDDs and other traditional end points for the topiramate, naltrexone, acamprosate, and placebo groups. Effect sizes of PSNHDDs were determined for each month of active treatment and by varying grace periods-early periods in the trial where outcome is not considered in the analysis-and were compared with that of other traditional outcome measures. Long-term outcomes were compared for groups that had no heavy drinking days versus those that had heavy drinking days during active treatment. PSNHDD effect sizes were significant for both topiramate (0.34 and 0.25 at months 2 and 3, respectively) and naltrexone (0.24 and 0.26 at months 3 and 4, respectively). Given a 2-month grace period for naltrexone, the effect size of PSNHDDs was comparable to the effect sizes using traditional outcome measures. With a 1-month grace period for topiramate, it was greater than the majority of traditional outcome measures. Little is gained by allowing up to 1, 2, or 3 heavy drinking days as an end point. Subjects with no HDDs during treatment fared better than those with some HDDs on drinking outcomes and alcohol-related consequences during a 1-year follow-up. PSNHDD appears to be a clinically informative end point measure, especially when used with a grace period, and is as sensitive as most traditional outcome measures in detecting differences between the medication and placebo groups. Nonetheless, these findings should be replicated in other clinical data sets

  7. Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

    Science.gov (United States)

    Williams, Mark R; Ward, Denham S; Carlson, Douglas; Cravero, Joseph; Dexter, Franklin; Lightdale, Jenifer R; Mason, Keira P; Miner, James; Vargo, John J; Berkenbosch, John W; Clark, Randall M; Constant, Isabelle; Dionne, Raymond; Dworkin, Robert H; Gozal, David; Grayzel, David; Irwin, Michael G; Lerman, Jerrold; O'Connor, Robert E; Pandharipande, Pratik; Rappaport, Bob A; Riker, Richard R; Tobin, Joseph R; Turk, Dennis C; Twersky, Rebecca S; Sessler, Daniel I

    2017-03-01

    The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

  8. Clinical outcomes of combined flow-pressure drop measurements using newly developed diagnostic endpoint: Pressure drop coefficient in patients with coronary artery dysfunction

    Science.gov (United States)

    Effat, Mohamed A; Peelukhana, Srikara Viswanath; Banerjee, Rupak K

    2016-01-01

    AIM: To combine pressure and flow parameter, pressure drop coefficient (CDP) will result in better clinical outcomes in comparison to the fractional flow reserve (FFR) group. METHODS: To test this hypothesis, a comparison was made between the FFR 27.9 groups in this study, for the major adverse cardiac events [major adverse cardiac events (MACE): Primary outcome] and patients’ quality of life (secondary outcome). Further, a comparison was also made between the survival curves for the FFR 27.9 groups. Two-tailed χ2 test proportions were performed for the comparison of primary and secondary outcomes. Kaplan-Meier survival analysis was performed to compare the survival curves of FFR 27.9 groups (MedcalcV10.2, Mariakerke, Belgium). Results were considered statistically significant for P 27.9 group (8.57%, 2 out of 35). Noteworthy is the reduction in the %MACE in the CDP > 27.9 group, in comparison to the FFR 27.9 groups. Survival analysis results suggest that the survival time for the CDP > 27.9 group (n = 35) is significantly higher (P = 0.048) in comparison to the survival time for the FFR < 0.75 group (n = 20). The results remained similar for a FFR = 0.80 cut-off. CONCLUSION: Based on the above, CDP could prove to be a better diagnostic end-point for clinical revascularization decision-making in the cardiac catheterization laboratories. PMID:27022460

  9. HIV-Related Stigma, Social Support, and Psychological Distress Among Individuals Initiating ART in Ethiopia.

    Science.gov (United States)

    Parcesepe, Angela; Tymejczyk, Olga; Remien, Robert; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Melaku, Zenebe; Elul, Batya; Nash, Denis

    2018-02-16

    Recent World Health Organization HIV treatment guideline expansion may facilitate timely antiretroviral therapy (ART) initiation. However, large-scale success of universal treatment strategies requires a more comprehensive understanding of known barriers to early ART initiation. This work aims to advance a more comprehensive understanding of interrelationships among three known barriers to ART initiation: psychological distress, HIV-related stigma, and low social support. We analyzed cross-sectional interview data on 1175 adults initiating ART at six HIV treatment clinics in Ethiopia. Experience of each form of HIV-related stigma assessed (e.g., anticipatory, internalized, and enacted) was associated with increased odds of psychological distress. However, among those who reported enacted HIV-related stigma, there was no significant association between social support and psychological distress. Interventions to improve mental health among people living with HIV should consider incorporating components to address stigma, focusing on strategies to prevent or reduce the internalization of stigma, given the magnitude of the relationship between high internalized stigma and psychological distress. Interventions to increase social support may be insufficient to improve the mental health of people living with HIV who experienced enacted HIV-related stigma. Future research should examine alternative strategies to manage the mental health consequences of enacted HIV-related stigma, including coping skills training.

  10. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Science.gov (United States)

    Ricotti, Valeria; Evans, Matthew R B; Sinclair, Christopher D J; Butler, Jordan W; Ridout, Deborah A; Hogrel, Jean-Yves; Emira, Ahmed; Morrow, Jasper M; Reilly, Mary M; Hanna, Michael G; Janiczek, Robert L; Matthews, Paul M; Yousry, Tarek A; Muntoni, Francesco; Thornton, John S

    2016-01-01

    A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (pmuscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  11. Age-related cataract in men in the selenium and vitamin e cancer prevention trial eye endpoints study: a randomized clinical trial.

    Science.gov (United States)

    Christen, William G; Glynn, Robert J; Gaziano, J Michael; Darke, Amy K; Crowley, John J; Goodman, Phyllis J; Lippman, Scott M; Lad, Thomas E; Bearden, James D; Goodman, Gary E; Minasian, Lori M; Thompson, Ian M; Blanke, Charles D; Klein, Eric A

    2015-01-01

    Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium. To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35,533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study. Individual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate). Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract. During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction. These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age

  12. Stimulating high impact HIV-related cardiovascular research: recommendations from a multidisciplinary NHLBI Working Group on HIV-related heart, lung, and blood disease.

    Science.gov (United States)

    Shah, Monica R; Cook, Nakela; Wong, Renee; Hsue, Priscilla; Ridker, Paul; Currier, Judith; Shurin, Susan

    2015-02-24

    The clinical challenges confronting patients with human immunodeficiency virus (HIV) have shifted from acquired immunodeficiency syndrome (AIDS)-related illnesses to chronic diseases, such as coronary artery disease, chronic lung disease, and chronic anemia. With the growing burden of HIV-related heart, lung, and blood (HLB) disease, the National Heart, Lung, and Blood Institute (NHLBI) recognizes it must stimulate and support HIV-related HLB research. Because HIV offers a natural, accelerated model of common pathological processes, such as inflammation, HIV-related HLB research may yield important breakthroughs for all patients with HLB disease. This paper summarizes the cardiovascular recommendations of an NHLBI Working Group, Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases, charged with identifying scientific priorities in HIV-related HLB disease and developing recommendations to promote multidisciplinary collaboration among HIV and HLB investigators. The working group included multidisciplinary sessions, as well as HLB breakout sessions for discussion of disease-specific issues, with common themes about scientific priorities and strategies to stimulate HLB research emerging in all 3 groups. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Measuring clinically relevant endpoints in a serum-free, three-dimensional, primary cell culture system of human osteoarthritic articular chondrocytes.

    Science.gov (United States)

    Bundens, Grace; Buckley, Andrea; Milton, LaBraya; Behling, Kathryn; Chmielewski, Sarah; Cho, Ellen; Lozano-Torres, Xiomara; Selim, Abdulhafez; Lackman, Richard; George-Weinstein, Mindy; Miller, Lawrence; D'Angelo, Marina

    2017-08-15

    Osteoarthritis (OA) is characterized by degeneration of articular cartilage within the joint, inflammation and pain. The purpose of this study was to develop a primary, serum free cell culture system of human osteoarthritic articular chondrocytes (HOACs) with which to study manifestations of the disease process. Joint tissues were obtained from OA patients undergoing total knee arthroplasty (TKA). HOACs isolated from the femoral condyles and tibial plateau of the same side were combined, plated in three-dimensional, alginate beads and cultured for five days in serum, hormone and protein free medium. More living cells were obtained from the femoral condyles than the tibial plateau. The optimal plating density was 2.5 × 106 cells/ml of alginate. The amounts of DNA, RNA, proteoglycans and total collagen were similar in cultures prepared from the sides of least and greatest pathology. More type 1 than type 2 collagen was detected in the medium on days 2 and 5. A greater percentage of type 1 than type 2 collagen was degraded. The inflammatory cytokine interleukin-1 beta was present in the medium and alginate associated matrix. Although variation in the metabolic profiles between subjects was observed, HOACs from all patients continued to reflect the OA phenotype for five days in culture. This serum free, three-dimensional primary culture system of HOACs provides a platform with which to measure clinically relevant endpoints of OA and screen potential disease modifying OA therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Statistical planning to address strongly correlated endpoints for inferential subgroups: An innovative approach for an illustrative clinical trial with complex multiplicity issues.

    Science.gov (United States)

    Sun, Hengrui; Binkowitz, Bruce; Koch, Gary G

    2017-01-01

    Multiplicity is an important statistical issue that arises in clinical trials when the efficacy of the test treatment is evaluated in multiple ways. The major concern for multiplicity is that uncontrolled multiple assessments lead to inflated family-wise Type I error, and they thereby undermine the integrity of the statistical inferences. Multiplicity comes from different sources, for example, making inferences either on the overall population or some pre-specified sub-populations, while multiple endpoints need to be evaluated for each population. Therefore, a sound statistical strategy that controls the family-wise Type I error rate in a strong sense, without excessive loss of power from over-control, is crucial for the success of the trial. For a recent phase III cardiovascular trial with such complex multiplicity, we illustrate the use of a closed testing strategy that begins with a global test; and subsequent testing only proceeds when the global test is rejected. Also, we discuss a simulation study based on this trial to compare the power of the illustrated closed testing strategy to some well-known alternative approaches. We found that this strategy can comprehensively meet most of the primary objectives of the trial effectively with reasonably high overall power.

  15. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

    Science.gov (United States)

    Bottomley, Andrew; Pe, Madeline; Sloan, Jeff; Basch, Ethan; Bonnetain, Franck; Calvert, Melanie; Campbell, Alicyn; Cleeland, Charles; Cocks, Kim; Collette, Laurence; Dueck, Amylou C; Devlin, Nancy; Flechtner, Hans-Henning; Gotay, Carolyn; Greimel, Eva; Griebsch, Ingolf; Groenvold, Mogens; Hamel, Jean-Francois; King, Madeleine; Kluetz, Paul G; Koller, Michael; Malone, Daniel C; Martinelli, Francesca; Mitchell, Sandra A; Moinpour, Carol M; Musoro, Jammbe; O'Connor, Daniel; Oliver, Kathy; Piault-Louis, Elisabeth; Piccart, Martine; Pimentel, Francisco L; Quinten, Chantal; Reijneveld, Jaap C; Schürmann, Christoph; Smith, Ashley Wilder; Soltys, Katherine M; Taphoorn, Martin J B; Velikova, Galina; Coens, Corneel

    2016-11-01

    Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

    OpenAIRE

    Erdman, L.K.; D'Acremont, V.; Hayford, K.; Rajwans, N.; Kilowoko, M.; Kyungu, E.; Hongoa, P.; Alamo, L.; Streiner, D.L.; Genton, B.; Kain, K.C.

    2015-01-01

    BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We stud...

  17. Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.

    Science.gov (United States)

    Kenny, Louise C; Black, Michael A; Poston, Lucilla; Taylor, Rennae; Myers, Jenny E; Baker, Philip N; McCowan, Lesley M; Simpson, Nigel A B; Dekker, Gus A; Roberts, Claire T; Rodems, Kelline; Noland, Brian; Raymundo, Michael; Walker, James J; North, Robyn A

    2014-09-01

    More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia. © 2014 American Heart Association, Inc.

  18. HIV-related stigma: implications for symptoms of anxiety and ...

    African Journals Online (AJOL)

    HIV-related stigma: implications for symptoms of anxiety and depression among Malawian women. ... African Journal of AIDS Research ... These findings suggest that interventions that reduce HIV-related stigma are likely to enhance psychological functioning among Malawian women, which in turn will improve the women's ...

  19. Understanding HIV-related posttraumatic stress disorder in South ...

    African Journals Online (AJOL)

    A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic review of the literature identified eight relevant studies that put current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%. Even the ...

  20. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Valeria Ricotti

    Full Text Available A number of promising experimental therapies for Duchenne muscular dystrophy (DMD are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function.15 non-ambulant DMD boys (mean age 13.3 y and 10 age-gender matched healthy controls (mean age 14.6 y were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.. Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation.Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001. A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7, accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9 and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8.These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  1. EBV AND HIV-RELATED LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Michele Bibas

    2009-12-01

    Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

  2. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 1: clinical trial design principles: A consensus document from the mitral valve academic research consortium.

    Science.gov (United States)

    Stone, Gregg W; Vahanian, Alec S; Adams, David H; Abraham, William T; Borer, Jeffrey S; Bax, Jeroen J; Schofer, Joachim; Cutlip, Donald E; Krucoff, Mitchell W; Blackstone, Eugene H; Généreux, Philippe; Mack, Michael J; Siegel, Robert J; Grayburn, Paul A; Enriquez-Sarano, Maurice; Lancellotti, Patrizio; Filippatos, Gerasimos; Kappetein, Arie Pieter

    2015-08-01

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Published on behalf of the European Society of Cardiology. All rights reserved. © American College of Cardiology

  3. HIV-Related Stigma, Shame, and Avoidant Coping: Risk Factors for Internalizing Symptoms Among Youth Living with HIV?

    Science.gov (United States)

    Bennett, David S; Hersh, Jill; Herres, Joanna; Foster, Jill

    2016-08-01

    Youth living with HIV (YLH) are at elevated risk of internalizing symptoms, although there is substantial individual variability in adjustment. We examined perceived HIV-related stigma, shame-proneness, and avoidant coping as risk factors of internalizing symptoms among YLH. Participants (N = 88; ages 12-24) completed self-report measures of these potential risk factors and three domains of internalizing symptoms (depressive, anxiety, and PTSD) during a regularly scheduled HIV clinic visit. Hierarchical regressions were conducted for each internalizing symptoms domain, examining the effects of age, gender, and maternal education (step 1), HIV-related stigma (step 2), shame- and guilt-proneness (step 3), and avoidant coping (step 4). HIV-related stigma, shame-proneness, and avoidant coping were each correlated with greater depressive, anxiety, and PTSD symptoms. Specificity was observed in that shame-proneness, but not guilt-proneness, was associated with greater internalizing symptoms. In multivariable analyses, HIV-related stigma and shame-proneness were each related to greater depressive and PTSD symptoms. Controlling for the effects of HIV-related stigma and shame-proneness, avoidant coping was associated with PTSD symptoms. The current findings highlight the potential importance of HIV-related stigma, shame, and avoidant coping on the adjustment of YLH, as interventions addressing these risk factors could lead to decreased internalizing symptoms among YLH.

  4. Cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    Energy Technology Data Exchange (ETDEWEB)

    Petretta, Mario [University Federico II, Department of Translational Medicine, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy)

    2014-09-15

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with {sup 123}I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of {sup 123}I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present

  5. EBV AND HIV-RELATED LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Andrea Antinori

    2009-11-01

    strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

  6. Methodological Issues in HIV-Related Social Research in Nigeria ...

    African Journals Online (AJOL)

    Methodological Issues in HIV-Related Social Research in Nigeria. ... like sexual mores and sexuality requires much more than a straightjacket social science method, such as simply doing a cross-section study and/or using interview schedule.

  7. Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles: A Consensus Document From the Mitral Valve Academic Research Consortium.

    Science.gov (United States)

    Stone, Gregg W; Vahanian, Alec S; Adams, David H; Abraham, William T; Borer, Jeffrey S; Bax, Jeroen J; Schofer, Joachim; Cutlip, Donald E; Krucoff, Mitchell W; Blackstone, Eugene H; Généreux, Philippe; Mack, Michael J; Siegel, Robert J; Grayburn, Paul A; Enriquez-Sarano, Maurice; Lancellotti, Patrizio; Filippatos, Gerasimos; Kappetein, Arie Pieter

    2015-07-21

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Molecular pathology endpoints useful for aging studies.

    Science.gov (United States)

    Niedernhofer, L J; Kirkland, J L; Ladiges, W

    2017-05-01

    The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Simultaneous inference of a binary composite endpoint and its components

    DEFF Research Database (Denmark)

    Große Ruse, Mareile; Ritz, Christian; Hothorn, Ludwig A.

    2017-01-01

    Binary composite endpoints offer some advantages as a way to succinctly combine evidence from a number of related binary endpoints recorded in the same clinical trial into a single outcome. However, as some concerns about the clinical relevance as well as the interpretation of such composite endp...

  10. Gender differences in HIV-related stigma in Kenya.

    Science.gov (United States)

    Mugoya, George C T; Ernst, Kacey

    2014-02-01

    Stigma associated with HIV/AIDS directly and indirectly drives HIV transmission. We examined how factors associated with HIV-related stigma differed by gender, using data from the 2008-2009 Kenya Demographic and Health Survey (KDHS). Descriptive, bivariate and multinomial logistic regression analyses were conducted on selected HIV-related stigma indicators for men and women. Bivariate analyses showed significant gender differences in the overall HIV Stigma index with a higher proportion of women than men presented at the highest stigma level (4.9% vs 2.7%, p differences were found in employment, marital status, ethnicity, region of residence, wealth and media exposure. Our results showed that women in the general Kenyan population had higher stigmatic attitudes than men. This was associated with differences in risk factor profile and confirmed previous literature on complexity of social-cultural factors associated with HIV-related stigma.

  11. Primary endpoint results of the OMEGA Study: One-year clinical outcomes after implantation of a novel platinum chromium bare metal stent

    Energy Technology Data Exchange (ETDEWEB)

    Wang, John C., E-mail: john.wang@medstar.net [MedStar Union Memorial Hospital, Baltimore MD (United States); Carrié, Didier, E-mail: carrie.didier@chu-toulouse.fr [Centre Hôpital Universitaire Rangueil, Toulouse (France); Masotti, Monica, E-mail: MASOTTI@clinic.ub.es [Hospital Clinic, University of Barcelona (Spain); Erglis, Andrejs, E-mail: a.a.erglis@stradini.lv [Pauls Stradins Clinical University Hospital, University of Latvia, Riga (Latvia); Mego, David, E-mail: David.Mego@arheart.com [Arkansas Heart Hospital, Little Rock, AR (United States); Watkins, Matthew W., E-mail: Matthew.Watkins@vtmednet.org [University of Vermont Medical Center, Burlington VT (United States); Underwood, Paul, E-mail: Paul.underwood@bsci.com [Boston Scientific, Marlborough MA USA (United States); Allocco, Dominic J., E-mail: Dominic.allocco@bsci.com [Boston Scientific, Marlborough MA USA (United States); Hamm, Christian W., E-mail: C.Hamm@kerckhoff-klinik.de [Kerckhoff Heart and Thoraxcenter, Bad Nauheim (Germany)

    2015-03-15

    Background/purpose: Bare metal stents (BMS) have similar rates of death and myocardial infarction (MI) compared to drug-eluting stents (DES). DES lower repeat revascularization rates compared to BMS, but may have higher rates of late stent thrombosis (ST) potentially due to impaired endothelialization requiring longer dual anti-platelet therapy (DAPT). OMEGA evaluated a novel BMS designed to have improved deliverability and radiopacity, in comparison to currently available platforms. Methods/materials: OMEGA was a prospective, multicenter, single-arm study enrolling 328 patients at 37 sites (US and Europe). Patients received the OMEGA stent (bare platinum chromium element stent) for the treatment of de novo native coronary artery lesions (≤ 28 mm long; diameter ≥ 2.25 mm to ≤ 4.50 mm). The primary endpoint was 9-month target lesion failure (TLF: cardiac death, target vessel-related MI, target lesion revascularization [TLR]) compared to a prespecified performance goal (PG) based on prior generation BMS. All major cardiac events were independently adjudicated. DAPT was required for a minimum of 1 month post procedure. Results: In the OMEGA study, the mean age was 65; 17% had diabetes mellitus. The primary endpoint was met; 9 month TLF rate was 11.5%, and the upper 1-sided 95% confidence bound of 14.79% was less than the prespecified PG of 21.2% (p < 0.0001). One-year event rates were low including a TLF rate of 12.8% and an ST rate of 0.6% at 12 months. Conclusions: One-year outcomes of OMEGA show low rates of TLF, revascularization and ST. This supports safety and efficacy of the OMEGA BMS for the treatment of coronary artery disease. - Highlights: • The OMEGA study evaluated a novel platinum chromium bare metal stent. • OMEGA enrolled 328 patients at 37 sites (US and Europe). • The primary endpoint of 9 month target lesion failure was 11.5%. • One-year event rates were low including an ST rate of 0.6% at 12 months.

  12. Development and validation of a brief computer-administered HIV-Related Health Literacy Scale (HIV-HL).

    Science.gov (United States)

    Ownby, Raymond L; Waldrop-Valverde, Drenna; Hardigan, Patrick; Caballero, Joshua; Jacobs, Robin; Acevedo, Amarilis

    2013-02-01

    Health literacy is related to a number of health status variables and has been associated with medication adherence in persons treated for HIV infection. Currently-available measures of health literacy require lengthy administration or have content or format limitations. In this paper we report the preliminary development and validation of a brief computer-administered health literacy test that includes content focused on medication adherence as well as questions based on a video simulation of an HIV-related clinical encounter. The measure shows significant relations with other measures of health literacy, HIV-related knowledge, and electronically-measured medication adherence. We also present receiver operating characteristic analyses that provide estimates of various scores' sensitivities and specificities so that the HIV-Related Health Literacy Scale can be used as a screening measure.

  13. Shared Contract-Obedient Endpoints

    Directory of Open Access Journals (Sweden)

    Étienne Lozes

    2012-12-01

    Full Text Available Most of the existing verification techniques for message-passing programs suppose either that channel endpoints are used in a linear fashion, where at most one thread may send or receive from an endpoint at any given time, or that endpoints may be used arbitrarily by any number of threads. The former approach usually forbids the sharing of channels while the latter limits what is provable about programs. In this paper we propose a midpoint between these techniques by extending a proof system based on separation logic to allow sharing of endpoints. We identify two independent mechanisms for supporting sharing: an extension of fractional shares to endpoints, and a new technique based on what we call reflexive ownership transfer. We demonstrate on a number of examples that a linear treatment of sharing is possible.

  14. The intermediate endpoint effect in logistic and probit regression.

    Science.gov (United States)

    MacKinnon, D P; Lockwood, C M; Brown, C H; Wang, W; Hoffman, J M

    2007-01-01

    An intermediate endpoint is hypothesized to be in the middle of the causal sequence relating an independent variable to a dependent variable. The intermediate variable is also called a surrogate or mediating variable and the corresponding effect is called the mediated, surrogate endpoint, or intermediate endpoint effect. Clinical studies are often designed to change an intermediate or surrogate endpoint and through this intermediate change influence the ultimate endpoint. In many intermediate endpoint clinical studies the dependent variable is binary, and logistic or probit regression is used. The purpose of this study is to describe a limitation of a widely used approach to assessing intermediate endpoint effects and to propose an alternative method, based on products of coefficients, that yields more accurate results. The intermediate endpoint model for a binary outcome is described for a true binary outcome and for a dichotomization of a latent continuous outcome. Plots of true values and a simulation study are used to evaluate the different methods. Distorted estimates of the intermediate endpoint effect and incorrect conclusions can result from the application of widely used methods to assess the intermediate endpoint effect. The same problem occurs for the proportion of an effect explained by an intermediate endpoint, which has been suggested as a useful measure for identifying intermediate endpoints. A solution to this problem is given based on the relationship between latent variable modeling and logistic or probit regression. More complicated intermediate variable models are not addressed in the study, although the methods described in the article can be extended to these more complicated models. Researchers are encouraged to use an intermediate endpoint method based on the product of regression coefficients. A common method based on difference in coefficient methods can lead to distorted conclusions regarding the intermediate effect.

  15. HIV-related neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Schütz SG

    2013-09-01

    Full Text Available Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP related to human immunodeficiency virus (HIV is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pain

  16. Factors associated with pregnant women's anticipations and experiences of HIV-related stigma in rural Kenya.

    Science.gov (United States)

    Cuca, Yvette P; Onono, Maricianah; Bukusi, Elizabeth; Turan, Janet M

    2012-01-01

    Pregnant women who fear or experience HIV-related stigma may not get care for their own health or medications to reduce perinatal transmission of HIV. This study examined factors associated with anticipating and experiencing HIV-related stigma among 1777 pregnant women attending antenatal care clinics in rural Kenya. Women were interviewed at baseline, offered HIV testing and care, and a sub-set was re-interviewed at 4-8 weeks postpartum. Women who were older, had less education, whose husbands had other wives, and who perceived community discrimination against people with HIV had significantly greater adjusted odds of anticipating HIV stigma. Over half of the HIV-positive women interviewed postpartum reported having experienced stigma, much of which was self-stigma. Women experiencing minor depression, and those whose family knew of their HIV status had significantly greater adjusted odds of experiencing stigma. Lack of women's empowerment, as well as depression, may be important risk factors for HIV-related stigma and discrimination.

  17. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  18. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    DEFF Research Database (Denmark)

    Keeling, Stephanie O; Landewe, Robert; van der Heijde, Desiree

    2007-01-01

    OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker...... of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants...

  19. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    HIV-related symptoms and management in HIV and antiretroviral therapy patients in KwaZulu-Natal, South Africa: A longitudinal study. ... Overall, the participants reported medications as the most frequently occurring management strategy, with the second being spiritual, and the third being complementary or traditional ...

  20. Adolescent Adjustment Before and After HIV-Related Parental Death.

    Science.gov (United States)

    Rotheram-Borus, Mary Jane; Weiss, Robert; Alber, Susan; Lester, Patricia

    2005-01-01

    The impact of HIV-related parental death on 414 adolescents was examined over a period of 6 years. The adjustment of bereaved adolescents was compared over 4 time periods relative to parental death and was also compared with the adjustment of nonbereaved adolescents. Bereaved adolescents had significantly more emotional distress, negative life…

  1. PALLIATIVE TREATMENT FOR HIV-RELATED KAPOSrS SARCOMA

    African Journals Online (AJOL)

    This ongoing study evaluated the effectiveness of palliative treatment in patients with HIV-related KS in the absence of. ART. The HIV situation has changed since antiretroviral therapy. (ARn became available: deaths from AIDS-related illnesses have been reduced by 75%. A projected reduction in new KS cases of 50 - 90% ...

  2. Raising awareness of HIV-related stigma and its associated ...

    African Journals Online (AJOL)

    HIV Aids will remain a problem for a long time. Many people with HIV/AIDS still live in fear of discovery because of the prevalent stigma and its associated prejudice and discrimination. This article examines how HIV-related stigma and its associated prejudice and discrimination can be addressed in a classroom ± in the field ...

  3. Understanding HIV-related posttraumatic stress disorder in South ...

    African Journals Online (AJOL)

    A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic ... Even the lower estimates suggest that PTSD in response to the trauma of being diagnosed and living with HIV is a significant mental health burden.

  4. Research Gaps in Neonatal HIV-Related Care | Davies | Southern ...

    African Journals Online (AJOL)

    However, both in South Africa and across sub-Saharan African, lack of boosted peri-partum prophylaxis for high-risk vertical transmission, loss to followup, and failure to initiate HIV-infected infants on antiretroviral therapy (ART) before disease progression are key remaining gaps in neonatal HIV-related care. In this issue of ...

  5. Improved Endpoints for Cancer Immunotherapy Trials

    Science.gov (United States)

    Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

    2010-01-01

    Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

  6. The imaging of HIV-related brain disease : clinical: imaging

    African Journals Online (AJOL)

    Furthermore, a correlation between declining cognitive function and the loss of ... and highly active antiretroviral therapy (HAART) is an important aspect of managing these conditions effec- tively.2 In ... sult in damage to white matter tracts in the brain.6 Once damage is established and related cognitive disorders ensue, the ...

  7. Power Calculations to Select Instruments for Clinical Trial Secondary Endpoints. A Case Study of Instrument Selection for Post-Traumatic Stress Symptoms in Subjects with Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Sjoding, Michael W; Schoenfeld, David A; Brown, Samuel M; Hough, Catherine L; Yealy, Donald M; Moss, Marc; Angus, Derek C; Iwashyna, Theodore J

    2017-01-01

    After the sample size of a randomized clinical trial (RCT) is set by the power requirement of its primary endpoint, investigators select secondary endpoints while unable to further adjust sample size. How the sensitivity and specificity of an instrument used to measure these outcomes, together with their expected underlying event rates, affect an RCT's power to measure significant differences in these outcomes is poorly understood. Motivated by the design of an RCT of neuromuscular blockade in acute respiratory distress syndrome, we examined how power to detect a difference in secondary endpoints varies with the sensitivity and specificity of the instrument used to measure such outcomes. We derived a general formula and Stata code for calculating an RCT's power to detect differences in binary outcomes when such outcomes are measured with imperfect sensitivity and specificity. The formula informed the choice of instrument for measuring post-traumatic stress-like symptoms in the Reevaluation of Systemic Early Neuromuscular Blockade RCT ( www.clinicaltrials.gov identifier NCT02509078). On the basis of published sensitivities and specificities, the Impact of Events Scale-Revised was predicted to measure a 36% symptom rate, whereas the Post-Traumatic Stress Symptoms instrument was predicted to measure a 23% rate, if the true underlying rate of post-traumatic stress symptoms were 25%. Despite its lower sensitivity, the briefer Post-Traumatic Stress Symptoms instrument provided superior power to detect a difference in rates between trial arms, owing to its higher specificity. Examining instruments' power to detect differences in outcomes may guide their selection when multiple instruments exist, each with different sensitivities and specificities.

  8. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study.

    Science.gov (United States)

    Kimball, A B; Sobell, J M; Zouboulis, C C; Gu, Y; Williams, D A; Sundaram, M; Teixeira, H D; Jemec, G B E

    2016-06-01

    Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Evaluate the novel, validated endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. HiSCR was more responsive to change than HS-PGA Response in this subpopulation. © 2015 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

  9. Lipoprotein(a) concentrations, apolipoprotein(a) isoforms and clinical endpoints in haemodialysis patients with type 2 diabetes mellitus: results from the 4D Study.

    Science.gov (United States)

    Kollerits, Barbara; Drechsler, Christiane; Krane, Vera; Lamina, Claudia; März, Winfried; Dieplinger, Hans; Ritz, Eberhard; Wanner, Christoph; Kronenberg, Florian

    2016-11-01

    High lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apolipoprotein(a) [apo(a)] isoforms are associated with cardiovascular disease and mortality in the general population. We examined the association of both with all-cause mortality and cardiovascular endpoints in haemodialysis patients with diabetes mellitus. This is a post hoc analysis of the prospective 4D Study (German Diabetes Dialysis Study) that evaluated atorvastatin compared with placebo in 1255 haemodialysis patients with type 2 diabetes mellitus (median follow-up 4 years). The association of natural logarithm-transformed Lp(a) concentrations (increment one unit) and apo(a) isoforms with outcomes was analysed by Cox proportional hazards regression. The influence of age (median 66 years) was evaluated by stratified survival analyses. The median baseline Lp(a) concentration was 11.5 mg/dL (IQR 5.0-41.8). A quarter of patients had at least one LMW apo(a) isoform. Increased Lp(a) concentrations were associated with all-cause mortality in the total group [hazard ratio (HR) 1.09 (95% CI 1.03-1.16), P = 0.004]. LMW apo(a) isoforms were only associated with all-cause mortality in patients ≤ 66 years [HR 1.38 (95% CI 1.05-1.80), P = 0.02]. The strongest association for Lp(a) concentrations and LMW apo(a) isoforms was found for death due to infection in patients ≤ 66 years [HR 1.39 (95% CI 1.14-1.71), P = 0.001; HR 2.17 (95% CI 1.26-3.75), P = 0.005]. Lp(a) concentrations were also associated with fatal stroke in patients ≤66 years of age [HR 1.54 (95% CI 1.05-2.24), P = 0.03]. Neither Lp(a) nor LMW apo(a) isoforms were associated with other atherosclerosis-related events. High Lp(a) concentrations and LMW apo(a) isoforms are risk predictors for all-cause mortality and death due to infection in haemodialysis patients with diabetes mellitus. These associations are modified by age. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  10. Analysis of HIV-related mortality data in a tertiary South African ...

    African Journals Online (AJOL)

    Analysis of HIV-related mortality data in a tertiary South African neurology unit, 2006 ... At the Steve Biko Academic Hospital, Pretoria, the Neurology Department has seen a steady increase in HIV-related neurology patients. ... Article Metrics.

  11. Research gaps in neonatal HIV-related care

    Directory of Open Access Journals (Sweden)

    Mary-Ann Davies

    2015-05-01

    Full Text Available The South African prevention of mother to child transmission programme has made excellentprogress in reducing vertical HIV transmission, and paediatric antiretroviral therapyprogrammes have demonstrated good outcomes with increasing treatment initiation inyounger children and infants. However, both in South Africa and across sub-Saharan African,lack of boosted peri-partum prophylaxis for high-risk vertical transmission, loss to followup,and failure to initiate HIV-infected infants on antiretroviral therapy (ART before diseaseprogression are key remaining gaps in neonatal HIV-related care. In this issue of the Southern African Journal of HIV Medicine, experts provide valuable recommendations for addressingthese gaps. The present article highlights a number of areas where evidence is lacking toinform guidelines and programme development for optimal neonatal HIV-related care.

  12. Research gaps in neonatal HIV-related care

    Directory of Open Access Journals (Sweden)

    Mary-Ann Davies

    2015-04-01

    Full Text Available The South African prevention of mother to child transmission programme has made excellentprogress in reducing vertical HIV transmission, and paediatric antiretroviral therapyprogrammes have demonstrated good outcomes with increasing treatment initiation inyounger children and infants. However, both in South Africa and across sub-Saharan African,lack of boosted peri-partum prophylaxis for high-risk vertical transmission, loss to followup,and failure to initiate HIV-infected infants on antiretroviral therapy (ART before diseaseprogression are key remaining gaps in neonatal HIV-related care. In this issue of the Southern African Journal of HIV Medicine, experts provide valuable recommendations for addressingthese gaps. The present article highlights a number of areas where evidence is lacking toinform guidelines and programme development for optimal neonatal HIV-related care.

  13. The search for an elusive cutoff remains: Problems of binary classification of heavy drinking as an endpoint for alcohol clinical trials.

    Science.gov (United States)

    Pearson, Matthew R; Bravo, Adrian J; Kirouac, Megan; Witkiewitz, Katie

    2017-02-01

    To examine whether a clinically meaningful alcohol consumption cutoff can be created for clinical samples, we used receiver operator characteristic (ROC) curves to derive gender-specific consumption cutoffs that maximized sensitivity and specificity in the prediction of a wide range of negative consequences from drinking. We conducted secondary data analyses using data from two large clinical trials targeting alcohol use disorders: Project MATCH (n=1726) and COMBINE (n=1383). In both studies, we found that the ideal cutoff for men and women that maximized sensitivity/specificity varied substantially both across different alcohol consumption variables and alcohol consequence outcomes. Further, the levels of sensitivity/specificity were poor across all consequences. These results fail to provide support for a clinically meaningful alcohol consumption cutoff and suggest that binary classification of levels of alcohol consumption is a poor proxy for maximizing sensitivity/specificity in the prediction of negative consequences from drinking. Future research examining consumption-consequence associations should take advantage of continuous measures of alcohol consumption and alternative approaches for assessing the link between levels of consumption and consequences (e.g., ecological momentary assessment). Clinical researchers should consider focusing more directly on the consequences they aim to reduce instead of relying on consumption as a proxy for more clinically meaningful outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Physical Abuse is Associated with HIV-related Drug Risk

    OpenAIRE

    Reddy, Madhavi K.; Anderson, Bradley J; Liebschutz, Jane; Stein, Michael D.

    2014-01-01

    Those who have experienced abuse may be prone to engaging in risky sexual behavior and risky drug use. The relationship between sexual abuse and risky behavior has been well established in the literature, but the association between physical abuse and risky drug use has been equivocal. We hypothesize that the experience of PTSD symptoms following physical abuse leads to risky drug use. Therefore, we examined the associations among physical abuse history, PTSD symptoms, and HIV-related drug ri...

  15. Influence of sexual abuse on HIV-related attitudes and behaviors in adolescent psychiatric inpatients.

    Science.gov (United States)

    Brown, L K; Kessel, S M; Lourie, K J; Ford, H H; Lipsitt, L P

    1997-03-01

    To investigate the associations between sexual abuse and human immunodeficiency virus (HIV)-related attitudes and behaviors of adolescents with a psychiatric disorder. HIV-related knowledge, attitudes, and behaviors were examined by self-report assessment of adolescents admitted to a psychiatric hospital (N = 100). A subsample (n = 30) completed a role-playing exercise regarding HIV-preventive behavior that was scored for the degree of effective communication by raters blind to the subjects' abuse history. HIV-related risk behaviors were prevalent, including unprotected sexual intercourse (67%) and multiple partners (27%) among the sexually active (71% of the total). Also frequent were alcohol and drug use (25%) and sharing cutting instruments (22%) among those engaged in self-cutting behavior (62%). The 38% of the sample identified as having a history of sexual abuse indicated significantly poorer self-efficacy concerning condom use than their peers. Abused females scored significantly lower on the self-efficacy of condom use scale and reported significantly more frequent alcohol use than nonabused females (p = .003). A hierarchical multiple regression that controlled for consistency of condom use and tolerance of people with acquired immunodeficiency syndrome found that abuse history uniquely accounted for 16% of the variance in condom use self-efficacy. Analysis of the videotaped role-play found that abused adolescents were significantly less competent and had more difficulty in effective communication than their peers (p = .003). A history of sexual abuse is associated with impaired safe sexual decision-making and HIV-preventive communication skills, even in this already at-risk group. This study also underscores the importance of actively addressing these issues in the context of clinical care.

  16. A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention.

    Science.gov (United States)

    Jenkins, David

    2008-09-01

    Human papilloma virus (HPV)-16 and -18 are responsible for approximately 70% of invasive cervical cancers worldwide. Other oncogenic HPV types account for almost all the remainder. Importantly, HPV-45 and -31 account for approximately 10%. HPV-18 and -45, along with HPV-16, are found in over 90% of endocervical adenocarcinomas. HPV-45 is the third most frequent HPV type in cervical carcinoma and adenocarcinoma. The AS04-adjuvanted vaccine Cervarix was developed against HPV-16 and -18 focusing on preventing cervical cancer by inducing durable protection against new infection. In clinical trials, it shows evidence of cross-protection against other important oncogenic HPV types using a range of clinicopathological and virological endpoints. The current evidence suggesting the cross-protective effect comes from its overall impact on precancerous lesions and on 12-month or more persistent oncogenic HPV infection, together with specific evidence of protection against incident and new persistent infection lasting 6 months or more with individual HPV types. The use of virological endpoints for such studies is discussed, in particular for cross-protection evaluation, in view of the lower frequency of many important oncogenic HPV types other than HPV-16 or -18 in precancerous lesions and the frequent presence of multiple HPV infections. Both of these factors complicate the interpretation of type-specific, vaccine-induced protection against cervical intraepithelial neoplasia (CIN) lesions, in which other HPV DNA types are found along with HPV-16 and -18. The observed high level of overall protection against clinicopathological lesions, including CIN2+ in the vaccinated subjects (regardless of their HPV DNA status), predicts a potentially broader impact of the vaccine in the prevention of HPV-related precancers that goes beyond HPV-16 and -18. The prevention of persistent infections by individual types such as HPV-45 provides specific information on the protection against that

  17. Treatment of facial erythema in patients with rosacea with topical brimonidine tartrate: correlation of patient satisfaction with standard clinical endpoints of improvement of facial erythema.

    Science.gov (United States)

    Fowler, J; Tan, J; Jackson, J M; Meadows, K; Jones, T; Jarratt, M; Leoni, M

    2015-03-01

    Once-daily brimonidine tartrate (BT) 0.5% gel was shown to provide significantly greater efficacy vs. vehicle for the treatment of facial erythema in patients with rosacea. To demonstrate that patient satisfaction with overall appearance is correlated with reduction in facial erythema, as measured by clinician and patient assessments. Data from two identical phase III, multicentre, randomized, controlled trials of moderate facial erythema of rosacea (study A: n = 260; study B: n = 293) with topical BT 0.5% compared to vehicle gel once-daily for 4 weeks were analysed. Correlations of Patient's Assessment of Appearance (PAA) with Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA) of erythema were evaluated by calculation of gamma statistics. PAA correlated with CEA post-application on Days 1, 15 and 29 for the intent-to-treat population and provided a median gamma value of 0.57 (min = 0.28, max = 0.61). PAA and PSA was also highly correlated post-application on Days 1, 15 and 29; with a median gamma value of 0.87 (min = 0.66, max = 0.89). Subjects who achieved a clinically meaningful improvement in both CEA and PSA scales were more likely to report satisfaction with the overall appearance of their skin (P < 0.001). Both one- and two-grade improvements in facial erythema assessed by subjects (PSA) and clinicians (CEA) correlate well with PAA, a patient-centered representation of meaningful change. © 2014 European Academy of Dermatology and Venereology.

  18. Voting for image scoring and assessment (VISA)--theory and application of a 2 + 1 reader algorithm to improve accuracy of imaging endpoints in clinical trials.

    Science.gov (United States)

    Gottlieb, Klaus; Hussain, Fez

    2015-02-19

    Independent central reading or off-site reading of imaging endpoints is increasingly used in clinical trials. Clinician-reported outcomes, such as endoscopic disease activity scores, have been shown to be subject to bias and random error. Central reading attempts to limit bias and improve accuracy of the assessment, two factors that are critical to trial success. Whether one central reader is sufficient and how to best integrate the input of more than one central reader into one output measure, is currently not known.In this concept paper we develop the theoretical foundations of a reading algorithm that can achieve both objectives without jeopardizing operational efficiency We examine the role of expert versus competent reader, frame scoring of imaging as a classification task, and propose a voting algorithm (VISA: Voting for Image Scoring and Assessment) as the most appropriate solution which could also be used to operationally define imaging gold standards. We propose two image readers plus an optional third reader in cases of disagreement (2 + 1) for ordinary scoring tasks. We argue that it is critical in trials with endoscopically determined endpoints to include the score determined by the site reader, at least in endoscopy clinical trials. Juries with more than 3 readers could define a reference standard that would allow a transition from measuring reader agreement to measuring reader accuracy. We support VISA by applying concepts from engineering (triple-modular redundancy) and voting theory (Condorcet's jury theorem) and illustrate our points with examples from inflammatory bowel disease trials, specifically, the endoscopy component of the Mayo Clinic Score of ulcerative colitis disease activity. Detailed flow-diagrams (pseudo-code) are provided that can inform program design.The VISA "2 + 1" reading algorithm, based on voting, can translate individual reader scores into a final score in a fashion that is both mathematically sound (by avoiding

  19. Bayesian model selection techniques as decision support for shaping a statistical analysis plan of a clinical trial: An example from a vertigo phase III study with longitudinal count data as primary endpoint

    Directory of Open Access Journals (Sweden)

    Adrion Christine

    2012-09-01

    Full Text Available Abstract Background A statistical analysis plan (SAP is a critical link between how a clinical trial is conducted and the clinical study report. To secure objective study results, regulatory bodies expect that the SAP will meet requirements in pre-specifying inferential analyses and other important statistical techniques. To write a good SAP for model-based sensitivity and ancillary analyses involves non-trivial decisions on and justification of many aspects of the chosen setting. In particular, trials with longitudinal count data as primary endpoints pose challenges for model choice and model validation. In the random effects setting, frequentist strategies for model assessment and model diagnosis are complex and not easily implemented and have several limitations. Therefore, it is of interest to explore Bayesian alternatives which provide the needed decision support to finalize a SAP. Methods We focus on generalized linear mixed models (GLMMs for the analysis of longitudinal count data. A series of distributions with over- and under-dispersion is considered. Additionally, the structure of the variance components is modified. We perform a simulation study to investigate the discriminatory power of Bayesian tools for model criticism in different scenarios derived from the model setting. We apply the findings to the data from an open clinical trial on vertigo attacks. These data are seen as pilot data for an ongoing phase III trial. To fit GLMMs we use a novel Bayesian computational approach based on integrated nested Laplace approximations (INLAs. The INLA methodology enables the direct computation of leave-one-out predictive distributions. These distributions are crucial for Bayesian model assessment. We evaluate competing GLMMs for longitudinal count data according to the deviance information criterion (DIC or probability integral transform (PIT, and by using proper scoring rules (e.g. the logarithmic score. Results The instruments under study

  20. Dealing with HIV-related stigma: a qualitative study of women outpatients from the Chris Hani Baragwanath Hospital.

    Science.gov (United States)

    Lekganyane, Robert; du Plessis, Gretchen

    2012-01-01

    HIV-related stigma is widely regarded as a key impediment to effective prevention and care. The purpose of this study was to explore HIV-infected women outpatients' experiences of stigma and the coping strategies that they devised to deal with it. Six HIV-infected women receiving antiretroviral treatment from the Nthabiseng Clinic of the Chris Hani Baragwanath Hospital participated in this qualitative study. HIV-related stigma was experienced by all the participants and was narrated as a sense of loss that gave rise to feelings of fear and shame. To cope with this, the women isolated themselves, became secretive about their health, disclosed strategically, and enlisted support. The elements of stigma and the coping strategies employed as uncovered in this study suggest a basis from which interventions aimed at assisting HIV-infected people to deal with stigma can be planned. Copyright © 2012 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  1. Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

    Science.gov (United States)

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Chan, Henry H; Alam, Murad; Tannous, Zeina; Anderson, R Rox

    2016-05-01

    Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Associations between health literacy, HIV-related knowledge, and information behavior among persons living with HIV in the Dominican Republic.

    Science.gov (United States)

    Stonbraker, Samantha; Smaldone, Arlene; Luft, Heidi; Cushman, Linda F; Lerebours Nadal, Leonel; Halpern, Mina; Larson, Elaine

    2017-12-29

    To determine the health literacy levels of persons living with human immunodeficiency virus (HIV) (PLWH) at a health clinic in the Dominican Republic (DR) and assess associations between health literacy, HIV-related knowledge, and health information behavior (how patients need, seek, receive, and use information). Cross-sectional, descriptive. Participants were 107 PLWH attending the Clinic. A theoretically based, 64-item survey assessing information behavior and HIV-related knowledge was administered in Spanish through individual interviews. Health literacy was assessed using the Short Assessment of Health Literacy-Spanish and English. On average, participants were 40.8 years old and had lived with HIV for 7.7 years. The majority (69.2%) had low health literacy. HIV-related knowledge and information behavior varied by health literacy level and uncertainty regarding a main indicator of disease progression, viral load, was demonstrated regardless of health literacy level. Participants with low health literacy were less likely to answer questions or answer questions correctly and many participants (39.2%) indicated viral transmission can occur through supernatural means. Findings demonstrate unmet information need and that information received may not always be understood. Methods to improve health education are needed to ensure patients receive health information in an understandable way. © 2017 Wiley Periodicals, Inc.

  3. Presidential Elections and HIV-Related National Policies and Programs.

    Science.gov (United States)

    Holtgrave, David R; Bonacci, Robert A; Valdiserri, Ronald O

    2017-03-01

    The November 2016 general election and subsequent voting of the Electoral College resulted in the selection of Donald Trump as President of the United States. The incoming Administration ran a campaign that indicated a desire for substantial change in health policy, including the repeal of the Affordable Care Act (ACA). President Trump has said very little directly about HIV programs and policies, but some campaign positions (such as the repeal of the ACA) would clearly and substantially impact the lives of persons living with HIV. In this editorial, we highlight important HIV-related goals to which we must recommit ourselves, and we underscore several key points about evidence-based advocacy that are important to revisit at any time (but most especially when there is a change in Administration).

  4. Understanding HIV-related stigma among Indonesian nurses

    Science.gov (United States)

    Waluyo, Agung; Culbert, Gabriel J.; Levy, Judith; Norr, Kathleen

    2014-01-01

    Evidence indicates widespread stigmatization of persons living with HIV (PLWH) in Indonesia. Such attitudes among health care workers could impede the country’s policies for effective diagnosis and medical treatment of PLWH. Nonetheless, research to guide interventions to reduce stigma in health care settings is lacking. Also, the contributions of workplace, religion, and HIV knowledge to nurses’ HIV-related stigma are poorly understood. Our cross-sectional study aimed to describe factors associated with nurses’ stigmatizing attitudes toward PLWH. Four hundred nurses recruited from 4 hospitals in Jakarta, Indonesia, were surveyed using the Nurse AIDS Attitude Scale (NAAS) to measure stigma. Stigmatizing attitudes were significantly predicted by education, HIV training, perceived workplace stigma, religiosity, Islamic religious identification, and affiliation with the Islamic hospital. HIV knowledge was not a significant predictor of stigmatizing attitudes. Organization changes fostering workplace diversity are likely to substantially reduce stigmatizing attitudes in nurses. PMID:24759060

  5. Factors Associated with Pregnant Women’s Anticipations and Experiences of HIV-related Stigma in Rural Kenya

    Science.gov (United States)

    Cuca, Yvette P.; Onono, Maricianah; Bukusi, Elizabeth; Turan, Janet M.

    2012-01-01

    Pregnant women who fear or experience HIV-related stigma may not get care for their own health or medications to reduce perinatal transmission of HIV. This study examined factors associated with anticipating and experiencing HIV-related stigma among 1,777 pregnant women attending antenatal care clinics in rural Kenya. Women were interviewed at baseline, offered HIV testing and care, and a sub-set was re-interviewed at 4–8 weeks postpartum. Women who were older, had less education, whose husbands had other wives, and who perceived community discrimination against people with HIV had significantly greater adjusted odds of anticipating HIV stigma. Over half of the HIV-positive women interviewed postpartum reported having experienced stigma, much of which was self-stigma. Women experiencing minor depression, and those whose family knew of their HIV status had significantly greater adjusted odds of experiencing stigma. Lack of women’s empowerment, as well as depression, may be important risk factors for HIV-related stigma and discrimination. PMID:22799618

  6. HIV-related sexual risk behavior among African American adolescent girls.

    Science.gov (United States)

    Danielson, Carla Kmett; Walsh, Kate; McCauley, Jenna; Ruggiero, Kenneth J; Brown, Jennifer L; Sales, Jessica M; Rose, Eve; Wingood, Gina M; Diclemente, Ralph J

    2014-05-01

    Latent class analysis (LCA) is a useful statistical tool that can be used to enhance understanding of how various patterns of combined sexual behavior risk factors may confer differential levels of HIV infection risk and to identify subtypes among African American adolescent girls. Data for this analysis is derived from baseline assessments completed prior to randomization in an HIV prevention trial. Participants were African American girls (n=701) aged 14-20 years presenting to sexual health clinics. Girls completed an audio computer-assisted self-interview, which assessed a range of variables regarding sexual history and current and past sexual behavior. Two latent classes were identified with the probability statistics for the two groups in this model being 0.89 and 0.88, respectively. In the final multivariate model, class 1 (the "higher risk" group; n=331) was distinguished by a higher likelihood of >5 lifetime sexual partners, having sex while high on alcohol/drugs, less frequent condom use, and history of sexually transmitted diseases (STDs), when compared with class 2 (the "lower risk" group; n=370). The derived model correctly classified 85.3% of participants into the two groups and accounted for 71% of the variance in the latent HIV-related sexual behavior risk variable. The higher risk class also had worse scores on all hypothesized correlates (e.g., self-esteem, history of sexual assault or physical abuse) relative to the lower risk class. Sexual health clinics represent a unique point of access for HIV-related sexual risk behavior intervention delivery by capitalizing on contact with adolescent girls when they present for services. Four empirically supported risk factors differentiated higher versus lower HIV risk. Replication of these findings is warranted and may offer an empirical basis for parsimonious screening recommendations for girls presenting for sexual healthcare services.

  7. Understanding HIV-Related Stigma and Discrimination in a "Blameless" Population

    Science.gov (United States)

    Cao, Xiaobin; Sullivan, Sheena G.; Xu, Jie; Wu, Zunyou

    2006-01-01

    HIV-related stigma and discrimination are major barriers to the successful control of HIV. Stigma is associated with the disease as well as the behaviors that lead to infection. A qualitative study was conducted to identify the reasons, sources, and types of HIV-related stigma prevalent in rural China. Eighty in-depth interviews were conducted…

  8. Screening for HIV-related PTSD: Sensitivity and specificity of the 17 ...

    African Journals Online (AJOL)

    number of HIV infections in the world.1 The overall prevalence of HIV in South Africa is estimated at 10.8%,. Screening for HIV-related PTSD: Sensitivity and specificity of the. 17-item Posttraumatic Stress. Diagnostic Scale (PDS) in identifying HIV-related PTSD among a South African sample. L Martin, D Fincham, A Kagee.

  9. HIV-related travel restrictions: trends and country characteristics

    Directory of Open Access Journals (Sweden)

    Felicia Chang

    2013-06-01

    Full Text Available Introduction: Increasingly, HIV-seropositive individuals cross international borders. HIV-related restrictions on entry, stay, and residence imposed by countries have important consequences for this mobile population. Our aim was to describe the geographical distribution of countries with travel restrictions and to examine the trends and characteristics of countries with such restrictions. Methods: In 2011, data presented to UNAIDS were used to establish a list of countries with and without HIV restrictions on entry, stay, and residence and to describe their geographical distribution. The following indicators were investigated to describe the country characteristics: population at mid-year, international migrants as a percentage of the population, Human Development Index, estimated HIV prevalence (age: 15–49, presence of a policy prohibiting HIV screening for general employment purposes, government and civil society responses to having non-discrimination laws/regulations which specify migrants/mobile populations, government and civil society responses to having laws/regulations/policies that present obstacles to effective HIV prevention, treatment, care, and support for migrants/mobile populations, Corruption Perception Index, and gross national income per capita. Results: HIV-related restrictions exist in 45 out of 193 WHO countries (23% in all regions of the world. We found that the Eastern Mediterranean and Western Pacific Regions have the highest proportions of countries with these restrictions. Our analyses showed that countries that have opted for restrictions have the following characteristics: smaller populations, higher proportions of migrants in the population, lower HIV prevalence rates, and lack of legislation protecting people living with HIV from screening for employment purposes, compared with countries without restrictions. Conclusion: Countries with a high proportion of international migrants tend to have travel restrictions

  10. HIV-related travel restrictions: trends and country characteristics.

    Science.gov (United States)

    Chang, Felicia; Prytherch, Helen; Nesbitt, Robin C; Wilder-Smith, Annelies

    2013-06-03

    Increasingly, HIV-seropositive individuals cross international borders. HIV-related restrictions on entry, stay, and residence imposed by countries have important consequences for this mobile population. Our aim was to describe the geographical distribution of countries with travel restrictions and to examine the trends and characteristics of countries with such restrictions. In 2011, data presented to UNAIDS were used to establish a list of countries with and without HIV restrictions on entry, stay, and residence and to describe their geographical distribution. The following indicators were investigated to describe the country characteristics: population at mid-year, international migrants as a percentage of the population, Human Development Index, estimated HIV prevalence (age: 15-49), presence of a policy prohibiting HIV screening for general employment purposes, government and civil society responses to having non-discrimination laws/regulations which specify migrants/mobile populations, government and civil society responses to having laws/regulations/policies that present obstacles to effective HIV prevention, treatment, care, and support for migrants/mobile populations, Corruption Perception Index, and gross national income per capita. HIV-related restrictions exist in 45 out of 193 WHO countries (23%) in all regions of the world. We found that the Eastern Mediterranean and Western Pacific Regions have the highest proportions of countries with these restrictions. Our analyses showed that countries that have opted for restrictions have the following characteristics: smaller populations, higher proportions of migrants in the population, lower HIV prevalence rates, and lack of legislation protecting people living with HIV from screening for employment purposes, compared with countries without restrictions. Countries with a high proportion of international migrants tend to have travel restrictions - a finding that is relevant to migrant populations and travel

  11. Use of Meta-Analysis for the Validation of Surrogate Endpoints and Biomarkers in Cancer Trials

    OpenAIRE

    Buyse, Marc

    2009-01-01

    This article discusses statistical approaches to the validation of surrogate biomarkers and endpoints. One approach that has been successfully used in oncology consists of estimating associations at two levels: the association between the surrogate and the clinical endpoint, called the individual-level association, and the association between the effects of treatment on the surrogate and the clinical endpoint, called the trial-level association. This approach requires data to be available fro...

  12. ENDPOINT PROTECTION SECURITY SYSTEM FOR AN ENTERPRISE

    OpenAIRE

    Ruotsalainen, Petri

    2013-01-01

    The thesis subscriber was Metso Shared Services Ltd. The objective was to find out if Microsoft Forefront Endpoint Protection 2010 (FEP) would be secure and cost-effective enough system to fulfill the requirements of the company’s endpoint protection security system. Microsoft FEP was compared and benchmarked with some other most significant endpoint protection products based on the requirements and definitions of the subscriber. The comparison and evaluation were based on investigation a...

  13. An Intersectional Perspective on Access to HIV-Related Healthcare for Transgender Women.

    Science.gov (United States)

    Lacombe-Duncan, Ashley

    2016-01-01

    Transgender women experience decreased access to HIV-related healthcare relative to cisgender people, in part due to pervasive transphobia in healthcare. This perspective describes intersectionality as a salient theoretical approach to understanding this disparity, moving beyond transphobia to explore how intersecting systems of oppression, including cisnormativity, sexism/transmisogyny, classism, racism, and HIV-related, gender nonconformity, substance use, and sex work stigma influence HIV-related healthcare access for transgender women living with HIV. This perspective concludes with a discussion of how intersectionality-informed studies can be enhanced through studying underexplored intersections and bringing attention to women's resiliency and empowerment.

  14. Surrogate endpoint analysis: an exercise in extrapolation.

    Science.gov (United States)

    Baker, Stuart G; Kramer, Barnett S

    2013-03-06

    Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.

  15. A review of the legal and ethical issues for the conduct of HIV-related research in prisons.

    Science.gov (United States)

    Lazzarini, Z; Altice, F L

    2000-01-01

    This article sets the stage for future discussions of expanding prisoners' access to clinical trials in an effort to move from commentary and recommendations to changes in practice. It describes barriers to access to clinical trials, the demographics of HIV/AIDS in prisons, the unique situation posed by the potential for HIV-related research in prisons, and examines briefly the history of prisoner research in the U.S. The article considers both ethical and legal responses to clinical trials in prisons, noting the potential for and limitations of legal actions. Finally, it makes recommendations for conditions necessary to conduct ethical research in prisons and calls for more cooperation between prison systems and HIV/AIDS clinical trials researchers to make expanded access to clinical trials a reality.

  16. Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

    Science.gov (United States)

    Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

    2017-08-15

    Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

  17. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

  18. Effect of education of primary health care workers on HIV-related oral lesions in Nairobi East district

    Directory of Open Access Journals (Sweden)

    Lucina N. Koyio

    2012-04-01

    Full Text Available Background. An estimated 90% of HIV-infected people are likely to develop oral lesions in the course of HIV infection. Oro-pharyngeal candidiasis (OPC, an early marker for HIV-infection, can be diagnosed during an oral examination (OE. Primary healthcare (PHC providers in Kenya are neither trained nor sufficiently equipped to perform this simple, cheap and non-invasive examination. The PHC system in Kenya offers an opportunity to integrate early recognition and management of oral lesions into general health care. This study aims to estimate the effect of a multifaceted intervention for PHC providers in training them to perform an OE. Specifically, our primary objective is to establish whether the intervention is effective in increasing: i the frequency of early detection of HIV-related oral lesions; and ii referral rates for HIV-testing. Design and methods. The study has been designed in two parts: a retrospective clinical data record study and a prospective cohort study with pre-post control group design, carried out in 2 administrative divisions in Nairobi East district. The intervention group will receive one day of training on recognition of HIV-related oral lesions and other common oral conditions. Reminder sessions will be held at individual health facilities. Routine tally sheets will be used to record all patients with HIV-related oral lesions, dental caries and periodontal disease. A convenience sample of all the PHC in a division will be used. It will not be possible to blind investigators or assessors. Expected impact of the study for Public Health. Early recognition and treatment of HIV infection influences long-term survival rates and will reduce healthcare expenditure.

  19. Home monitoring improves endpoint efficiency in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Johannson, Kerri A; Vittinghoff, Eric; Morisset, Julie; Lee, Joyce S; Balmes, John R; Collard, Harold R

    2017-07-01

    The objective of this study was to investigate the reliability, feasibility and analytical impact of home-based measurement of forced vital capacity (FVC) and dyspnoea as clinical endpoints in idiopathic pulmonary fibrosis (IPF).Patients with IPF performed weekly home-based assessment of FVC and dyspnoea using a mobile hand-held spirometer and self-administered dyspnoea questionnaires. Weekly variability in FVC and dyspnoea was estimated, and sample sizes were simulated for a hypothetical 24-week clinical trial using either traditional office-based interval measurement or mobile weekly assessment.In total, 25 patients were enrolled. Mean adherence to weekly assessments over 24 weeks was greater than 90%. Compared with change assessment using baseline and 24-week measurements only, weekly assessment of FVC resulted in enhanced precision and power. For example, a hypothetical 24-week clinical trial with FVC as the primary endpoint would require 951 patients using weekly home spirometry compared with 3840 patients using office spirometry measures at weeks 1 and 24 only. The ability of repeated measures to reduce clinical trial sample size was influenced by the correlation structure of the data.Home monitoring can improve the precision of endpoint assessments, allowing for greater efficiency in clinical trials of therapeutics for IPF. Copyright ©ERS 2017.

  20. Five criteria for using a surrogate endpoint to predict treatment effect based on data from multiple previous trials.

    Science.gov (United States)

    Baker, Stuart G

    2017-11-21

    A surrogate endpoint in a randomized clinical trial is an endpoint that occurs after randomization and before the true, clinically meaningful, endpoint that yields conclusions about the effect of treatment on true endpoint. A surrogate endpoint can accelerate the evaluation of new treatments but at the risk of misleading conclusions. Therefore, criteria are needed for deciding whether to use a surrogate endpoint in a new trial. For the meta-analytic setting of multiple previous trials, each with the same pair of surrogate and true endpoints, this article formulates 5 criteria for using a surrogate endpoint in a new trial to predict the effect of treatment on the true endpoint in the new trial. The first 2 criteria, which are easily computed from a zero-intercept linear random effects model, involve statistical considerations: an acceptable sample size multiplier and an acceptable prediction separation score. The remaining 3 criteria involve clinical and biological considerations: similarity of biological mechanisms of treatments between the new trial and previous trials, similarity of secondary treatments following the surrogate endpoint between the new trial and previous trials, and a negligible risk of harmful side effects arising after the observation of the surrogate endpoint in the new trial. These 5 criteria constitute an appropriately high bar for using a surrogate endpoint to make a definitive treatment recommendation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  1. Translational endpoints in fragile X syndrome.

    Science.gov (United States)

    de Esch, Celine E F; Zeidler, Shimriet; Willemsen, Rob

    2014-10-01

    Fragile X syndrome (FXS) occurs in less than 10% of the intellectually disabled (ID) population. The cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units within the first exon of the FMR1 gene, which leads to hypermethylation and consequently silencing of the FMR1 gene. The lack of FMR1's gene product, the fragile X mental retardation protein (FMRP) in neurons is the cause of the ID in patients with FXS. FMRP plays an important role in local protein synthesis at the synapse including modulation of synaptic plasticity. The advancing knowledge about the cellular function of FMRP has led to the identification of translational endpoints for future therapeutic intervention strategies. This review highlights the challenging routes to the identification of reliable outcome measures in preclinical studies using both cellular models and Fmr1 knockout mice. Finally, clinical studies carried out to correct intellectual and behavioral deficits in patients with FXS, using a variety of existing and new drugs, are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. HIV-related discrimination reported by people living with HIV in London, UK.

    Science.gov (United States)

    Elford, Jonathan; Ibrahim, Fowzia; Bukutu, Cecilia; Anderson, Jane

    2008-03-01

    The objective was to examine the extent to which people living with HIV in London reported being discriminated against because of their infection. In 2004-2005, people living with HIV attending NHS outpatient HIV clinics in north east London were asked: "Have you ever been treated unfairly or differently because of your HIV status-in other words discriminated against?". Of the 1,687 people who returned a questionnaire (73% response rate), data from 1,385 respondents were included in this analysis; 448 heterosexual women and 210 heterosexual men of black African origin, 727 gay/bisexual men (621 white, 106 ethnic minority). Overall, nearly one-third of respondents (29.9%, 414/1,385) said they had been discriminated against because of their HIV infection. Of those who reported experiencing HIV-related discrimination, almost a half (49.6%, 200/403) said this had involved a health care worker including their dentist (n = 102, 25.3%) or primary care physician (n = 70, 17.4%).

  3. HIV-Related Healthcare Needs and Access Barriers for Brazilian Transgender and Gender Diverse People.

    Science.gov (United States)

    Costa, Angelo Brandelli; Fontanari, Anna Martha Vaitses; Catelan, Ramiro Figueiredo; Schwarz, Karine; Stucky, Juliana Ledur; da Rosa Filho, Heitor Tome; Pase, Paola Fagundes; Gagliotti, Daniel Augusto Mori; Saadeh, Alexandre; Lobato, Maria Inês Rodrigues; Nardi, Henrique Caetano; Koller, Silvia Helena

    2018-01-03

    The aim of this study is to investigate HIV-related healthcare needs and access barriers for Brazilian transgender and gender diverse people. Data were collected from gender identity clinics and the questionnaire was also made available on the Internet. Out of the 543 participants-62.1% (n = 337) transgender women, 28.7 (n = 156) transgender men and 9.2% (n = 50) gender diverse people, 63.7% had been tested at least once in their lives. The prevalence of self-reported HIV-positive status among transgender women was 16.5%, of which 92.0% reported having a physician with whom they regularly consulted about HIV, whereas none of the transgender men or gender diverse people reported HIV-positive status. In addition, 8.2% of transgender men and 12.5% of gender diverse people did not know their serological status. Finally, 71.0% of the participants were unfamiliar with post-exposure prophylaxis. The study discusses the need for adequate behavior-oriented HIV health policies and training of healthcare professionals regarding the needs of Brazilian transgender and gender diverse people.

  4. Alveolar macrophages as a cell source of cytokine hyperproduction in HIV-related interstitial lung disease.

    Science.gov (United States)

    Agostini, C; Sancetta, R; Cerutti, A; Semenzato, G

    1995-11-01

    Pulmonary macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). They are known to be discrete target cells for human immunodeficiency virus (HIV), and compelling evidence is accumulating that alveolar macrophages (AMs) from HIV-infected patients behave as versatile secretory cells that, acting as antigen-presenting cells, release a great variety of cytokines. The secretory products of AMs, pivotal to their immune effects, may contribute to localized immune dysregulation as well as to primary lung damage and clinical disease. Pulmonary macrophages are also thought to facilitate retroviral spread by their direct infection, by presenting HIV antigens to uninfected T cells, and by secreting cytokines that transactivate HIV expression. This review briefly considers the events underlying the role of AMs in the pulmonary defense mechanisms against HIV and AIDS-related opportunistic infections. Following a brief overview of immune mechanisms taking place in the lungs of HIV-infected subjects, we describe the specific role of AMs in the immune mechanisms devoted to recognizing and removing HIV-infected cells and controlling the local growth of opportunists. The pathogenetic role envisaged for macrophages in lung damage are also reviewed in the context of the known biology of these cells. Finally, this review examines the relevance of the retroviral infection of AMs in terms of pathogenesis of the HIV-related interstitial lung disease.

  5. Knowledge of HIV-related disabilities and challenges in accessing care: Qualitative research from Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Lena Morgon Banks

    Full Text Available While the rapid expansion in antiretroviral therapy access in low and middle income countries has resulted in dramatic declines in mortality rates, many people living with HIV face new or worsening experiences of disability. As nearly 1 in 20 adults are living with HIV in sub-Saharan Africa-many of whom are likely to develop disabling sequelae from long-term infection, co-morbidities and side effects of their treatment-understanding the availability and accessibility of services to address HIV-related disabilities is of vital importance. The aim of this study thus is to explore knowledge of HIV-related disabilities amongst stakeholders working in the fields of HIV and disability and factors impacting uptake and provision of interventions for preventing, treating or managing HIV-related disabilities.In-depth, semi-structured interviews were conducted with ten stakeholders based in Harare, Zimbabwe, who were working in the fields of either disability or HIV. Stakeholders were identified through a priori stakeholder analysis. Thematic Analysis, complemented by constant comparison as described in Grounded Theory, was used to analyse findings.All key informants reported some level of knowledge of HIV-related disability, mostly from observations made in their line of work. However, they reported no interventions or policies were in place specifically to address HIV-related disability. While referrals between HIV and rehabilitation providers were not uncommon, no formal mechanisms had been established for collaborating on prevention, identification and management. Additional barriers to accessing and providing services to address HIV-related disabilities included: the availability of resources, including trained professionals, supplies and equipment in both the HIV and rehabilitation sectors; lack of disability-inclusive adaptations, particularly in HIV services; heavy centralization of available services in urban areas, without accessible, affordable

  6. HIV-Related Stigma and Discriminatory Attitudes among a Semi-Urban Population.

    Science.gov (United States)

    Lugova, Halyna; Mon, Aye Aye; Daher, Aqil Mohammad; Suleiman, Adlina

    2015-09-01

    Stigma and discriminatory attitudes (SDAs) have a negative impact on human immunodeficiency virus (HIV) prevention, testing, and treatment as well as on family and social networks. There is a lack of understanding about HIV-related SDAs among people living outside large cities. This study is aimed to determine the level of HIV-related SDAs among a semi-urban population in Malaysia and to compare the SDA results among people with different sociodemographic characteristics. A sample of 106 respondents was generated by convenience sampling during the screening campaign in Alor Gajah, Malaysia. Data collection was carried out based on a pre-tested questionnaire via face-to-face interviews. More than half of the respondents (62.3%) thought that an HIV-positive teacher should not be allowed to continue teaching at school; 81.1% were unsure or were unwilling to care for their family member with AIDS at home; 81.2% thought children with HIV/AIDS should not continue to be raised in families; and 77.3% thought they would not reveal if a family member had HIV/AIDS. Priority should be given to evidence-based interventions to reduce HIV-related SDAs. This study did not reveal any significant relationship between sociodemographic profiles and HIV-related SDAs. Therefore, further research with a larger sample size is needed to investigate the underlying causes of HIV-related SDAs.

  7. Gendered aspects of perceived and internalized HIV-related stigma in China.

    Science.gov (United States)

    Li, Li; Lin, Chunqing; Ji, Guoping

    2017-10-01

    Although studies have demonstrated that females experience more HIV-related stigma than males do, questions remain regarding the different dimensions of the stigma (i.e., perceived versus internalized) in China. The present study investigated gender differences in perceived and internalized HIV-related stigma, taking into account the potential influence of education. The study was conducted between October 2011 and March 2013. A total of 522 people living with HIV (PLH) were recruited from Anhui Province, China. The PLH participated in a survey using the Computer Assisted Personal Interview (CAPI) method. The gender differences in perceived and internalized HIV-related stigma were calculated with and without stratifying by education level. Female participants had significantly less education than the male participants. No significant difference was observed between females and males with respect to perceived stigma. However, females reported significantly higher internalized stigma than males did (p stigma remained significant among educated participants (p = .038). The findings suggested that gender differences in HIV-related stigma were primarily found for internalized stigma. Heightened intervention efforts are encouraged to reduce internalized HIV-related stigma, particularly among female PLH in China and other regions with similar gender dynamics.

  8. Establishing a group of endpoints in a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  9. Gender and ethnicity differences in HIV-related stigma experienced by people living with HIV in Ontario, Canada.

    Science.gov (United States)

    Loutfy, Mona R; Logie, Carmen H; Zhang, Yimeng; Blitz, Sandra L; Margolese, Shari L; Tharao, Wangari E; Rourke, Sean B; Rueda, Sergio; Raboud, Janet M

    2012-01-01

    This study aimed to understand gender and ethnicity differences in HIV-related stigma experienced by 1026 HIV-positive individuals living in Ontario, Canada that were enrolled in the OHTN Cohort Study. Total and subscale HIV-related stigma scores were measured using the revised HIV-related Stigma Scale. Correlates of total stigma scores were assessed in univariate and multivariate linear regression. Women had significantly higher total and subscale stigma scores than men (total, median = 56.0 vs. 48.0, pgender-ethnicity interaction term was significant in multivariate analysis: Black women and Asian/Latin-American/Unspecified men reported the highest HIV-related stigma scores. Gender and ethnicity differences in HIV-related stigma were identified in our cohort. Findings suggest differing approaches may be required to address HIV-related stigma based on gender and ethnicity; and such strategies should challenge racist and sexist stereotypes.

  10. Quantum Endpoint Detection Based on QRDA

    Science.gov (United States)

    Wang, Jian; Wang, Han; Song, Yan

    2017-10-01

    Speech recognition technology is widely used in many applications for man - machine interaction. To face more and more speech data, the computation of speech processing needs new approaches. The quantum computation is one of emerging computation technology and has been seen as useful computation model. So we focus on the basic operation of speech recognition processing, the voice activity detection, to present quantum endpoint detection algorithm. In order to achieve this algorithm, the n-bits quantum comparator circuit is given firstly. Then based on QRDA(Quantum Representation of Digital Audio), a quantum endpoint detection algorithm is presented. These quantum circuits could efficient process the audio data in quantum computer.

  11. Polymorphic Endpoint Types for Copyless Message Passing

    Directory of Open Access Journals (Sweden)

    Viviana Bono

    2011-07-01

    Full Text Available We present PolySing#, a calculus that models process interaction based on copyless message passing, in the style of Singularity OS. We equip the calculus with a type system that accommodates polymorphic endpoint types, which are a variant of polymorphic session types, and we show that well-typed processes are free from faults, leaks, and communication errors. The type system is essentially linear, although linearity alone may leave room for scenarios where well-typed processes leak memory. We identify a condition on endpoint types that prevents these leaks from occurring.

  12. Forecasting interest rates with shifting endpoints

    DEFF Research Database (Denmark)

    Van Dijk, Dick; Koopman, Siem Jan; Wel, Michel van der

    2014-01-01

    We consider forecasting the term structure of interest rates with the assumption that factors driving the yield curve are stationary around a slowly time-varying mean or ‘shifting endpoint’. The shifting endpoints are captured using either (i) time series methods (exponential smoothing) or (ii......) long-range survey forecasts of either interest rates or inflation and output growth, or (iii) exponentially smoothed realizations of these macro variables. Allowing for shifting endpoints in yield curve factors provides substantial and significant gains in out-of-sample predictive accuracy, relative...... to stationary and random walk benchmarks. Forecast improvements are largest for long-maturity interest rates and for long-horizon forecasts....

  13. Psychological reactance and HIV-related stigma among women living with HIV.

    Science.gov (United States)

    Brown, Monique J; Serovich, Julianne M; Kimberly, Judy A; Hu, Jinxiang

    2016-01-01

    Psychological reactance is defined as the drive to re-establish autonomy after it has been threatened or constrained. People living with HIV may have high levels of psychological reactance due to the restrictions that they may perceive as a result of living with HIV. People living with HIV may also exhibit levels of HIV-related stigma. The relationship between psychological reactance and HIV-related stigma is complex yet understudied. Therefore, the main aim of this study was to examine the association between psychological reactance and HIV-related stigma among women living with HIV. Data were obtained from one time-point (a cross-sectional assessment) of a longitudinal HIV disclosure study. Psychological reactance was measured using the 18-item Questionnaire for the Measurement of Psychological Reactance. HIV-related stigma was measured using the HIV Stigma Scale, which has four domains: personalized, disclosure concerns, negative self-image, and concerns with public attitudes. Principal component analysis was used to derive components of psychological reactance. Linear regression models were used to determine the association between overall psychological reactance and its components, and stigma and its four domains, and depressive and anxiety symptoms. The associations between stigma and mental health were also examined. Three components of psychological reactance were derived: Opposition, Irritability, and Independence. Overall psychological reactance and irritability were associated with all forms of stigma. Opposition was linked to overall and negative self-image stigma. Overall psychological reactance, opposition, and irritability were positively associated with anxiety symptoms while opposition was also associated with Centers for Epidemiologic Studies-Depression depressive symptoms. There were also positive associations between all forms of stigma, and depressive and anxiety symptoms. Health-care providers and counselors for women living with HIV

  14. HIV-related stigma in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

    Science.gov (United States)

    Ion, Allyson; Wagner, Anne C; Greene, Saara; Loutfy, Mona R

    2017-02-01

    HIV-related stigma is associated with many psychological challenges; however, minimal research has explored how perceived HIV-related stigma intersects with psychosocial issues that mothers living with HIV may experience including depression, perceived stress and social isolation. The present study aims to describe the correlates and predictors of HIV-related stigma in a cohort of women living with HIV (WLWH) from across Ontario, Canada during pregnancy and early postpartum. From March 2011 to December 2012, WLWH ≥ 18 years (n = 77) completed a study instrument measuring independent variables including sociodemographic characteristics, perceived stress, depression symptoms, social isolation, social support and perceived racism in the third trimester and 3, 6 and 12 months postpartum. Multivariable linear regression was employed to explore the relationship between HIV-related stigma and multiple independent variables. HIV-related stigma generally increased from pregnancy to postpartum; however, there were no significant differences in HIV-related stigma across all study time points. In multivariable regression, depression symptoms and perceived racism were significant predictors of overall HIV-related stigma from pregnancy to postpartum. The present analysis contributes to our understanding of HIV-related stigma throughout the pregnancy-motherhood trajectory for WLWH including the interactional relationship between HIV-related stigma and other psychosocial variables, most notably, depression and racism.

  15. Unseen risks: HIV-related risk behaviors among ethnically diverse sexual minority adolescent females.

    Science.gov (United States)

    Thoma, Brian C; Huebner, David M; Rullo, Jordan E

    2013-12-01

    High rates of HIV-related sexual risk behaviors among lesbian and bisexual female adolescents have been documented. However, previous research has not adequately described racial/ethnic subgroup differences in risk behaviors within this population. We examined HIV-related sexual risk behaviors among an ethnically diverse sample of sexual minority girls (N = 244). Compared to their White peers, girls who identified their race/ethnicity as mixed had more than four times the odds of reporting both unprotected vaginal sex with a male and multiple male sex partners. All subgroups exhibited risk behaviors, indicating that sexual minority girls must be included in HIV-prevention efforts targeting adolescent females.

  16. HIV-related restrictions on entry, residence and stay in the WHO European Region: a survey

    DEFF Research Database (Denmark)

    Lazarus, Jeff; Curth, Nadja; Weait, Matthew

    2010-01-01

    Back in 1987, the World Health Organization (WHO) concluded that the screening of international travellers was an ineffective way to prevent the spread of HIV. However, some countries still restrict the entrance and/or residency of foreigners with an HIV infection. HIV-related travel restrictions...... have serious implications for individual and public health, and violate internationally recognized human rights. In this study, we reviewed the current situation regarding HIV-related travel restrictions in the 53 countries of the WHO European Region....

  17. Use of nutrigenomics endpoints in dietary interventions

    NARCIS (Netherlands)

    Hendriks, H.F.J.

    2013-01-01

    In this paper, the nutrigenomics approach is discussed as a research tool to study the physiological effects of nutrition and consequently how nutrition affects health and disease (endpoints). Nutrigenomics is the study of the effects of foods and food constituents on gene expression; the analyses

  18. Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

    Science.gov (United States)

    Stout, Stephanie A.; Litvak, Margarita; Robbins, Natashia M.; Sandberg, David E.

    2010-01-01

    Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development. PMID:20976294

  19. Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

    Directory of Open Access Journals (Sweden)

    Sandberg DavidE

    2010-08-01

    Full Text Available Psychological outcomes in persons with congenital adrenal hyperplasia (CAH have received substantial attention. The objectives of this paper were to (1 catalog psychological endpoints assessed in CAH outcome studies and (2 classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68% investigated endpoints related to psychosexual differentiation. The preponderance of studies (76% examined a direct relationship (i.e., inferring causality between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

  20. HIV-related stigma and NGO-isation in India: a historico-empirical analysis.

    Science.gov (United States)

    Nambiar, Devaki

    2012-06-01

    In response to World Bank critiques in 2007, the Indian Ministry of Health and Family Welfare declared that human immunodeficiency virus (HIV)-related stigma was a barrier to the participation of non-governmental organisations (NGOs) in the implementation of HIV prevention targeted interventions. Taking a deeper view of HIV-related stigma as a historically inflected process of devaluation, this article details the history and transformation of NGO involvement in the HIV epidemic from 1986 through economic liberalisation in the 1990s up to the Second National AIDS Control Programme (NACP II 1999-2006). It additionally examines findings from interviews and participant observation of NGO workers (N = 24) from four targeted intervention NGOs in Delhi funded under NACP II. Analysis reveals that a second wave of HIV-related NGO involvement has mushroomed in the past two decades, affording NGO workers multiple pathways to credibility in the Indian response to the epidemic. Contradictions embedded in the overlap of these pathways produce stigma, reflecting 'adverse incorporation' of the NGO workers. Drawing upon noteworthy exceptions to this trend from the first wave of Indian HIV-related NGOs, the article calls for NGO participation as an explicitly political project of addressing the social inequalities that shape stigma as well as vulnerability to illness writ large. © 2011 The Author. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  1. Positive coping strategies and HIV-related stigma in south India.

    Science.gov (United States)

    Kumar, Shuba; Mohanraj, Rani; Rao, Deepa; Murray, Katherine R; Manhart, Lisa E

    2015-03-01

    Whether perceived or enacted, HIV-related stigma is widespread in India, and has had a crippling effect on People Living with HIV/AIDS (PLHA). Research has shown that a positive attitude towards the illness sets a proactive framework for the individual to cope with his or her infection; therefore, healthy coping mechanisms are essential to combat HIV-related stigma. This qualitative study involving in-depth interviews and focus group discussions with PLHA affiliated with HIV support groups in South India explored positive coping strategies employed by PLHA to deal with HIV-related stigma. Interviews and focus group discussions were translated, transcribed, and analyzed for consistent themes. Taboos surrounding modes of transmission, perceiving sex workers as responsible for the spread of HIV, and avoiding associating with PLHA provided the context of HIV-related stigma. Despite these challenges, PLHA used several positive strategies, classified as Clear Knowledge and Understanding of HIV, Social Support and Family Well-Being, Selective Disclosure, Employment Building Confidence, and Participation in Positive Networks. Poor understanding of HIV and fears of being labeled immoral undermined healthy coping behavior, while improved understanding, affiliation with support groups, family support, presence of children, and financial independence enhanced PLHA confidence. Such positive coping behaviours could inform culturally relevant interventions.

  2. Associations between HIV-related stigma, self-esteem, social support, and depressive symptoms in Namibia.

    Science.gov (United States)

    Kalomo, Eveline Ndii

    2017-10-11

    The current study sought to investigate the association between HIV-related stigma, self-esteem, social support, and depression of people living with HIV and AIDS (PLWHA) in Namibia. Purposive sampling was used to recruit a total of 124 men and women living with HIV/AIDS in the Katima Mulilo region of northern Namibia. A cross-sectional survey was used to collect information on demographics, self-esteem, social support, HIV-related stigma, and depression. Correlation analysis revealed that HIV-related stigma, self-esteem, and social support were all significantly correlated with depression. Further, Ordinary Least Squares (OLS) regression analysis indicated that HIV-related stigma was the largest risk factor and self-esteem was the largest protective factor with respect to depressive symptoms. Findings indicated the necessity of appropriate assessment and intervention for psychosocial distress among PLWHA. Helping professionals should design evidence-based interventions that address individual and societal challenges that impact people living with HIV and AIDS.

  3. Barriers to men who have sex with men attending HIV related health ...

    African Journals Online (AJOL)

    2014-04-22

    Apr 22, 2014 ... discrimination affect MSM attendance to HIV related health services; (ii) determine how health care worker's (HCW's) practices and .... Level of education. No formal education. 2. Primary. 15. Vocational training. 1. Secondary. 32. Employment. Unemployed. 19. Self-employed. 23. Employed. 8. Sexual.

  4. First report of HIV-related oral manifestations in Mali | Tamí-Maury ...

    African Journals Online (AJOL)

    The objective of this study was to determine the prevalence of HIV-related oral manifestations (OM) during the first month of ART therapy in a Malian health facility. Methods: Medical records of adult patients who initiated ART regimens at the Gabriel Touré Hospital, Mali (2001 to 2008) were randomly identified. Multiple ...

  5. HIV-related disabilities: an extra burden to HIV and AIDS healthcare ...

    African Journals Online (AJOL)

    Issues also arose from disability and stigma that were perceived as affecting adherence to antiretroviral treatment. In addition, healthcare workers encounter challenges in dealing with the increased needs of care and support for those people living with HIV who experience HIV-related disabilities. They indicated a limited ...

  6. Barriers to men who have sex with men attending HIV related health ...

    African Journals Online (AJOL)

    The HIV/ AIDS disease burden is disproportionately high among men who have sex with men (MSM) worldwide. If this group will continue to be ignored they will continue to be the focus of HIV infection to the general population. This study explored barriers impeding MSM utilizing the HIV related health services currently ...

  7. Attachment relationships of preschool aged children of mothers with HIV and HIV-related psychosis

    NARCIS (Netherlands)

    Spies, R.; Sterkenburg, P.S.; Schuengel, C.; van Rensburg, E

    2016-01-01

    Children from mothers with HIV-related psychosis are frequently raised in challenging contexts, yet the extent to which these children grow up in insecure or disordered attachment relationships is unknown. Using the Strange Situation Procedure the distribution of attachment relationships of children

  8. First report of HIV-related oral manifestations in Mali | Tamí-Maury ...

    African Journals Online (AJOL)

    Introduction: In 2004, the sudden availability of free antiretroviral therapy (ART in Mali, within the context of an already overburdened health care system created gaps in individual patient quality of care. The objective of this study was to determine the prevalence of HIV-related oral manifestations (OM) during the first month ...

  9. A Survey Of HIV-Related Knowledge And Attitude Among Dental ...

    African Journals Online (AJOL)

    Objective: To assess HIV-related knowledge and attitude among dental nursing students in South Western Nigeria. Methods: A descriptive cross-sectional survey of the entire 97 final year dental nursing students from 4 colleges of health technology located in South Western Nigeria was conducted in University of Benin ...

  10. HIV-related tuberculosis: how well are we doing with current control efforts?

    NARCIS (Netherlands)

    Maher, D.; Borgdorff, M.; Boerma, T.

    2005-01-01

    The top 25 human immunodeficiency virus (HIV) prevalence countries. To review the current status of implementation of interventions to control HIV-related tuberculosis (TB). Using data on national TB and HIV programme activities from the most recent national survey results published by international

  11. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  12. HIV-related disabilities: an extra burden to HIV and AIDS healthcare workers?

    Science.gov (United States)

    van Egeraat, Leonie; Hanass-Hancock, Jill; Myezwa, Hellen

    2015-01-01

    Healthcare workers have been at the forefront of dealing with the impact of HIV and AIDS at all stages of the pandemic. This brings new challenges to include disability into HIV care. However, the implications for healthcare workers in an already fragile health system along with HIV-related disabilities in persons living with HIV are little understood. This study examined the healthcare workers' perspective on disability in HIV care. This article describes a qualitative study using in-depth interviews with 10 healthcare workers in a semi-urban hospital setting in KwaZulu-Natal, South Africa. The study aimed to understand healthcare workers' experiences with disability in the context of HIV. The International Classification of Functioning Disability and Health (ICF) was used as a guiding framework to understand disability. Healthcare workers described HIV-related disabilities on all three levels of disability, namely impairments/ body function, activity limitations and participation restrictions, as affecting the livelihood of their patients and household members. Issues also arose from disability and stigma that were perceived as affecting adherence to antiretroviral treatment. In addition, healthcare workers encounter challenges in dealing with the increased needs of care and support for those people living with HIV who experience HIV-related disabilities. They indicated a limited ability to cope and respond to these needs. Primarily they arrange additional referrals to manage complex or episodic disabilities. Participants also identified issues such as excessive work load, lack of resources and training and emotional challenges in dealing with disability. Healthcare workers need support to respond to the increased needs of people living with HIV who have HIV-related disabilities. Responses need to reflect: 1) increase in rehabilitative staff including in community outreach programmes; 2) skills training in HIV-related disability; and 3) psychosocial support for

  13. HIV-related stigma among African, Caribbean, and Black youth in Windsor, Ontario.

    Science.gov (United States)

    Mihan, Robert; Kerr, Jelani; Maticka-Tyndale, Eleanor

    2016-01-01

    HIV-related stigma has been shown to undermine prevention, care, treatment, and the well-being of people living with HIV. A disproportion burden of HIV infection, as well as elevated levels of HIV-related stigma, is evidenced in sub-Saharan African (SSA) and African-diasporic populations. This study explores factors that influence HIV-related stigma among 16- to 25-year-old youth residing in a Canadian city who identify as African, Caribbean, or Black. Stigma, as rooted in cultural norms and beliefs and related social institutions, combined with insights from research on stigma in SSA and African-diasporic populations, guided the development of a path analytic structural equation model predicting levels of HIV-related stigmatizing attitudes. The model was tested using survey responses of 510 youth to estimate the direct and indirect influences of ethno-religious identity, religious service attendance, time in Canada, HIV/AIDS knowledge, HIV-testing history, sexual health service contact, and gender on HIV-related stigma. Statistically significant negative associations were found between levels of stigma and knowledge and HIV-testing history. Ethno-religious identity and gender had both direct and indirect effects on stigma. African-Muslim participants had higher levels of stigma, lower knowledge, and were less likely to have been tested for HIV infection than other ethno-religious groups. Male participants had higher levels of stigma and lower knowledge than women. Time in Canada had only indirect effects on stigma, with participants in Canada for longer periods having higher knowledge and less likely to have been tested than more recent arrivals. While the strength of the effect of knowledge on stigmatizing attitudes in this research is consistent with other research on stigma and evaluations of stigma-reduction programs, the path analytic results provide additional information about how knowledge and HIV-testing function as mediators of non

  14. HIV-related stigma in African and Afro-Caribbean communities in the Netherlands: manifestations, consequences and coping

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Shiripinda, I.; de Bruin, M.; Pryor, J.B.; Schaalma, H.P.

    2012-01-01

    HIV-related stigma in African and Afro-Caribbean diaspora communities in the Netherlands was investigated. Interviews with HIV-positive and HIV-negative community members demonstrated that HIV-related stigma manifests as social distance, physical distance, words and silence. The psychological

  15. HIV-related stigma in African and Afro-Caribbean communities in the Netherlands: Manifestations, consequences and coping

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Shiripinda, I.; Bruin, M. de; Pryor, J.B.; Schaalma, H.P.

    2012-01-01

    HIV-related stigma in African and Afro-Caribbean diaspora communities in the Netherlands was investigated. Interviews with HIV-positive and HIV-negative community members demonstrated that HIV-related stigma manifests as social distance, physical distance, words and silence. The psychological

  16. New prospects for nelfinavir in non-HIV-related diseases.

    Science.gov (United States)

    Brüning, Ansgar; Gingelmaier, Andrea; Friese, Klaus; Mylonas, Ioannis

    2010-06-01

    Nelfinavir (Viracept) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes.

  17. Prevalence of HIV-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda

    Directory of Open Access Journals (Sweden)

    Taremwa IM

    2015-04-01

    Full Text Available Ivan M Taremwa,1 Winnie R Muyindike,2 Enoch Muwanguzi,1 Yap Boum II,1,3 Bernard Natukunda1 1Department of Medical Laboratory Sciences, Faculty of Medicine, Mbarara University of Science and Technology, 2Immune Suppression Syndrome Clinic, Mbarara Regional Referral Hospital, 3Epicentre Mbarara Research Centre, Mbarara, Uganda Aims/objectives: We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda.Materials and methods: This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA technique.Results: We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42 years, and there were 63.2% (n=9,500 females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%. The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4% among antiretroviral therapy (ART-naïve clients (n=2,675 and was 13.0% (95% CI: 0.3%–21.9% for clients who were on ART (n=6. The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05. Two of the 40 participants (5.0% had antiplatelet antibodies.Conclusion: This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of

  18. New science-based endpoints to accelerate oncology drug development.

    Science.gov (United States)

    Kelloff, Gary J; Sigman, Caroline C

    2005-03-01

    Although several new oncology drugs have reached the market, more than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. These factors contribute to the high costs of oncology drug development and clearly show the need for faster, more cost-effective strategies for evaluating oncology drugs and better definition of patients who will benefit from treatment. Remarkable advances in the understanding of neoplastic progression at the cellular and molecular levels have spurred the discovery of molecularly targeted drugs. This progress along with advances in imaging and bioassay technologies are the basis for describing and evaluating new biomarker endpoints as well as for defining other biomarkers for identifying patient populations, potential toxicity, and providing evidence of drug effect and efficacy. Definitions and classifications of these biomarkers for use in oncology drug development are presented in this paper. Science-based and practical criteria for validating biomarkers have been developed including considerations of mechanistic plausibility, available methods and technology, and clinical feasibility. New promising tools for measuring biomarkers have also been developed and are based on genomics and proteomics, direct visualisation by microscopy (e.g., confocal microscopy and computer-assisted image analysis of cellular features), nanotechnologies, and direct and remote imaging (e.g., fluorescence endoscopy and anatomical, functional and molecular imaging techniques). The identification and evaluation of potential surrogate endpoints and other biomarkers require access to and analysis of large amounts of data, new technologies and extensive research resources. Further, there is a requirement for a convergence of research, regulatory and drug developer

  19. Should Associations between HIV-Related Risk Perceptions and Behaviors or Intentions Be Positive or Negative?

    Science.gov (United States)

    Tsui, Hiyi; Lau, Joseph T. F.; Xiang, Weina; Gu, Jing; Wang, Zixin

    2012-01-01

    Risk perceptions are important in HIV research and interventions; mixed results were found between HIV-related perceptions and behaviors. We interviewed 377 sexually active injecting drug users in China, finding mixed associations between HIV-related risk perception assessed by two general measures and two previous risk behaviors (syringe sharing: p.05) – partially supporting the ‘reflective hypothesis’ that reflection on previous behaviors increases risk perceptions. When we use specific measures for risk perceptions (HIV transmission via unprotected sex with specific types of sex partner and via syringe sharing) and use behavioral intention to adopt protective risk behaviors (condom use and avoid syringe sharing totally) as dependent variables, positive significant associations were observed – supporting the motivational hypothesis that risk perceptions motivate one to adopt protective behaviors. The direction and significance of the associations of concern depends on types of measures used. It has important implications on research design, data interpretation and services. PMID:23284896

  20. Workplace and HIV-related sexual behaviours and perceptions among female migrant workers

    OpenAIRE

    Yang, H.; Li, X.; Stanton, B; Fang, X; Lin, D.; Mao, R; LIU, H.; Chen, X.; SEVERSON, R.

    2005-01-01

    Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment esta...

  1. Cutis Verticis Gyrata in Men Affected by HIV-Related Lipodystrophy

    Directory of Open Access Journals (Sweden)

    Keshav Khanijow

    2013-01-01

    Full Text Available We report the occurrence of cutis verticis gyrata (CVG, a disfiguring dermatological condition, in four patients with HIV-related lipodystrophy (HIVLD. These four patients had abnormal metabolic and hormonal lab values which we compare with metabolic and hormonal perturbations cited in previous HIVLD cohorts. In addition, we describe the sole use of poly-L-lactic acid as a potential treatment for decreasing the appearance of CVG-associated ridges.

  2. Social cohesion, social participation, and HIV related risk among female sex workers in Swaziland.

    Science.gov (United States)

    Fonner, Virginia A; Kerrigan, Deanna; Mnisi, Zandile; Ketende, Sosthenes; Kennedy, Caitlin E; Baral, Stefan

    2014-01-01

    Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social cohesion among sex workers and social participation of sex workers in the larger community, and HIV-related risk in Swaziland using respondent-driven sampling. Relationships between social cohesion, social participation, and HIV-related risk factors were assessed using logistic regression. HIV prevalence among the sample was 70.4% (223/317). Social cohesion was associated with consistent condom use in the past week (adjusted odds ratio [AOR] = 2.25, 95% confidence interval [CI]: 1.30-3.90) and was associated with fewer reports of social discrimination, including denial of police protection. Social participation was associated with HIV testing (AOR = 2.39, 95% CI: 1.36-4.03) and using condoms with non-paying partners (AOR = 1.99, 95% CI: 1.13-3.51), and was inversely associated with reported verbal or physical harassment as a result of selling sex (AOR = 0.55, 95% CI: 0.33-0.91). Both social capital constructs were significantly associated with collective action, which involved participating in meetings to promote sex worker rights or attending HIV-related meetings/ talks with other sex workers. Social- and structural-level interventions focused on building social cohesion and social participation among sex workers could provide significant protection from HIV infection for female sex workers in Swaziland.

  3. Social Cohesion, Social Participation, and HIV Related Risk among Female Sex Workers in Swaziland

    Science.gov (United States)

    Fonner, Virginia A.; Kerrigan, Deanna; Mnisi, Zandile; Ketende, Sosthenes; Kennedy, Caitlin E.; Baral, Stefan

    2014-01-01

    Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social cohesion among sex workers and social participation of sex workers in the larger community, and HIV-related risk in Swaziland using respondent-driven sampling. Relationships between social cohesion, social participation, and HIV-related risk factors were assessed using logistic regression. HIV prevalence among the sample was 70.4% (223/317). Social cohesion was associated with consistent condom use in the past week (adjusted odds ratio [AOR]  = 2.25, 95% confidence interval [CI]: 1.30–3.90) and was associated with fewer reports of social discrimination, including denial of police protection. Social participation was associated with HIV testing (AOR = 2.39, 95% CI: 1.36–4.03) and using condoms with non-paying partners (AOR = 1.99, 95% CI: 1.13–3.51), and was inversely associated with reported verbal or physical harassment as a result of selling sex (AOR = 0.55, 95% CI: 0.33–0.91). Both social capital constructs were significantly associated with collective action, which involved participating in meetings to promote sex worker rights or attending HIV-related meetings/ talks with other sex workers. Social- and structural-level interventions focused on building social cohesion and social participation among sex workers could provide significant protection from HIV infection for female sex workers in Swaziland. PMID:24498125

  4. The changing epidemiology of HIV-related chronic kidney disease in the era of antiretroviral therapy.

    Science.gov (United States)

    Mallipattu, Sandeep K; Salem, Fadi; Wyatt, Christina M

    2014-08-01

    The epidemiology of kidney disease in HIV-infected individuals has changed significantly since the introduction of combination antiretroviral therapy (cART) in the mid 1990s. HIV-associated nephropathy (HIVAN), an aggressive form of collapsing focal segmental glomerulosclerosis (FSGS) caused by direct HIV infection of the kidney in a genetically susceptible host, emerged early in the HIV epidemic as a leading cause of end-stage renal disease. With the widespread use of cART, HIVAN is increasingly rare in populations with access to care, and the spectrum of HIV-related chronic kidney disease now reflects the growing burden of comorbid disease in the aging HIV population. Nonetheless, available data suggest that both HIV infection and cART nephrotoxicity continue to contribute to the increased risk of chronic kidney disease in HIV-infected individuals in the United States and Europe. Despite the genetic susceptibility to HIVAN in individuals of West African descent, limited data are available to define the prevalence and spectrum of HIV-related kidney disease in sub-Saharan Africa, which is home to two-thirds of the world's HIV population. In this mini-review, we characterize the changing epidemiology of HIV-related chronic kidney disease in Western nations and in sub-Saharan Africa.

  5. [Retrospective research on proportion of HIV related death causes in nine counties in China].

    Science.gov (United States)

    Gao, Xing; Wang, Ning; Wang, Lu; Qin, Qian-qian; Wang, Li-yan; Li, Dong-min; Wang, Lan; Wang, Yan-he; Ding, Guo-wei; Ding, Zheng-wei

    2008-12-01

    To investigate the proportion of HIV related death cause, and its years of potential life lost (YPLL) and work years of potential life lose (WYPLL) in project counties. According to the protocol of the third national death causes surveillance and HIV related death causes surveillance, retrospective study was implemented including baseline investigation of deaths' name list, demography information, door-to-door interview and death causes deduction in Gejiu, Ruili and Longchuan county in Yunnan province, Yangdong county in Guangdong province, Luzhai county in Guangxi zhuang Autonomous Region, Weishi and Zhecheng county in Henan province, Xishui county in Hubei province and Gu'an county in Hebei province. The study was conducted among nine counties located in seven provinces. A total of 118 719 cases were included, raw mortality was 5.83 per thousand, 2002 death cases were related to HIV, which contributed 1.67% of total deaths. The average age of HIV death was 38.03 yearsow, which was earlier than the non-HIV-related life-span (63.10 years). The YPLL and WYPLL of HIV death was 33.80 years and 20.50 years, respectively, which had contributed the second highest average YPLL. HIV has an important proportion among all death causes, and has contributed severe average YPLL and WYPLL.

  6. Hyponatremia, acute kidney injury, and mortality in HIV-related toxoplasmic encephalitis

    Directory of Open Access Journals (Sweden)

    Alexandre B. Libório

    2012-12-01

    Full Text Available BACKGROUND: There are no reports on hyponatremia and acute kidney injury (AKI involved in the course of HIV-related toxoplasmic encephalitis (TE. The main objective of this study was to describe the occurrence of hyponatremia and its relationship with AKI and mortality in HIV-related toxoplasmic encephalitis (TE. METHODS: This was a retrospective cohort study on patients with HIV-related TE. AKI was considered only when the RIFLE (risk, injury, failure, loss, end-stage criterion was met, after the patient was admitted. RESULTS: A total of 92 patients were included, with a mean age of 36 ± 9 years. Hyponatremia at admission was observed in 43 patients (46.7%, with AKI developing in 25 (27.1% patients during their hospitalization. Sulfadiazine was the treatment of choice in 81% of the cases. Death occurred in 13 cases (14.1%. Low serum sodium level correlated directly with AKI and mortality. Male gender (OR 7.89, 95% CI 1.22-50.90, p = 0.03 and hyponatremia at admission (OR 4.73, 95% CI 1.22-18.30, p = 0.02 were predictors for AKI. Independent risk factors for death were AKI (OR 8.3, 95% CI 1.4-48.2, p < 0.0001 and hyponatremia (or 9.9, 95% ci 1.2-96.3, p < 0.0001. CONCLUSION: AKI and hyponatremia are frequent in TE. Hyponatremia on admission is highly associated with AKI and mortality.

  7. Hyponatremia, acute kidney injury, and mortality in HIV-related toxoplasmic encephalitis

    Directory of Open Access Journals (Sweden)

    Alexandre B. Libório

    Full Text Available BACKGROUND: There are no reports on hyponatremia and acute kidney injury (AKI involved in the course of HIV-related toxoplasmic encephalitis (TE. The main objective of this study was to describe the occurrence of hyponatremia and its relationship with AKI and mortality in HIV-related toxoplasmic encephalitis (TE. METHODS: This was a retrospective cohort study on patients with HIV-related TE. AKI was considered only when the RIFLE (risk, injury, failure, loss, end-stage criterion was met, after the patient was admitted. RESULTS: A total of 92 patients were included, with a mean age of 36 ± 9 years. Hyponatremia at admission was observed in 43 patients (46.7%, with AKI developing in 25 (27.1% patients during their hospitalization. Sulfadiazine was the treatment of choice in 81% of the cases. Death occurred in 13 cases (14.1%. Low serum sodium level correlated directly with AKI and mortality. Male gender (OR 7.89, 95% CI 1.22-50.90, p = 0.03 and hyponatremia at admission (OR 4.73, 95% CI 1.22-18.30, p = 0.02 were predictors for AKI. Independent risk factors for death were AKI (OR 8.3, 95% CI 1.4-48.2, p < 0.0001 and hyponatremia (or 9.9, 95% ci 1.2-96.3, p < 0.0001. CONCLUSION: AKI and hyponatremia are frequent in TE. Hyponatremia on admission is highly associated with AKI and mortality.

  8. HIV-related Burkitt lymphoma with florid granulomatous reaction: an unusual case with good outcome

    Science.gov (United States)

    Li, Jin-Nan; Gao, Li-Min; Wang, Wei-Ya; Chen, Min; Li, Gan-Di; Liu, Wei-Ping; Zhang, Wen-Yan

    2014-01-01

    Burkitt lymphoma (BL) is a highly aggressive subtype of non-Hodgkin lymphomas (NHL). Lymphoma related granulomatous reaction rarely occurs in sporadic BL. Herein, we describe the first case of HIV related Burkitt lymphoma with florid granulomatous reaction. A 41-year-old HIV-positive Chinese male presented lymphadenopathy in the right cervical region for 3 months. The enlarged lymph node biopsies revealed the presence of prominent granulomas of varying size with Langhans giant cells, leading to the misdiagnosis of tuberculous lymphadenitis in other hospital. Subsequently, the case was sent to us for consultation. The morphology, immunophenotype, special staining, interphase FISH analysis and blood tests confirmed a diagnosis of HIV related Burkitt lymphoma with granulomatous reaction. Without radiotherapy and chemotherapy, the patient was alive and well with no evidence of lymphoma during the observation period of 24 months. The case suggested that lymphoma with florid granulomatous reaction can easily be misdiagnosed as benign lesions since the large number of epithelioid granulomas could obscure the primary lesion. Moreover, the granulomatous reaction may be an indicator for favorable prognosis in HIV related Burkitt lymphoma. PMID:25400794

  9. Assessment of HIV-related stigma in a US faith-based HIV education and testing intervention

    Directory of Open Access Journals (Sweden)

    Jannette Y Berkley-Patton

    2013-11-01

    Full Text Available Introduction: The African American church is a highly influential institution with the potential to greatly increase the reach of HIV prevention interventions and address HIV-related stigma in US African American communities. However, there are few studies on HIV-related stigma and African American church populations. This study explored HIV-related stigma among church and community members participating in an HIV education and testing intervention pilot study in African American churches, named Taking It to the Pews. Methods: Four African American churches located in Kansas City, MO and KS, were randomized to either intervention or comparison groups. Churches assigned to the intervention group received religiously tailored HIV education, testing and compassion messages/activities (e.g. sermons, brochures/church bulletins, testimonials via the Taking It to the Pews HIV Tool Kit. Comparison churches received non-religiously tailored HIV information. HIV-related stigma was assessed with 543 church members and with community members served through church outreach services (e.g. food/clothing pantries, social services in the four churches. Participants completed surveys at baseline, 6 months and 12 months to assess their HIV-related stigma beliefs, exposure to intervention components and satisfaction with the study. Results: At baseline, HIV-related stigma beliefs were similar across experimental groups and were quite low. Mean HIV-related stigma scores were not significantly different between experimental groups at 6 months (p=0.92 or at 12 months (p=0.70. However, mean HIV-related stigma scores within both groups showed decreasing trends at six months, which approached significance. Analysis of previously studied HIV-related stigma factors (e.g. age, gender, income, HIV knowledge, religiosity did not yield changes in the null findings. Intervention group participants were highly exposed to several intervention components (sermons, HIV resource

  10. Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis

    Science.gov (United States)

    Katz, Ingrid T; Ryu, Annemarie E; Onuegbu, Afiachukwu G; Psaros, Christina; Weiser, Sheri D; Bangsberg, David R; Tsai, Alexander C

    2013-01-01

    Introduction Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical

  11. Refining Current Scientific Priorities and Identifying New Scientific Gaps in HIV-Related Heart, Lung, Blood, and Sleep Research.

    Science.gov (United States)

    Twigg, Homer L; Crystal, Ronald; Currier, Judith; Ridker, Paul; Berliner, Nancy; Kiem, Hans-Peter; Rutherford, George; Zou, Shimian; Glynn, Simone; Wong, Renee; Peprah, Emmanuel; Engelgau, Michael; Creazzo, Tony; Colombini-Hatch, Sandra; Caler, Elisabet

    2017-09-01

    The National Heart, Lung, and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood, and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14-15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: (1) HIV-related HLBS comorbidities in the antiretroviral era; (2) HIV cure; (3) HIV prevention; and (4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV. The 2015 Working Group represented an opportunity for the NHLBI to obtain expert advice on HIV/AIDS scientific priorities and approaches over the next decade.

  12. HIV-Related Sexual Risk among African American Men Preceding Incarceration: Associations with Support from Significant Others, Family, and Friends

    National Research Council Canada - National Science Library

    Coatsworth, Ashley M; Scheidell, Joy D; Wohl, David A; Whitehead, Nicole E; Golin, Carol E; Judon-Monk, Selena; Khan, Maria R

    2017-01-01

    We evaluated the association between social support received from significant others, family, and friends and HIV-related sexual risk behaviors among African American men involved in the criminal justice system...

  13. Use of nutrigenomics endpoints in dietary interventions.

    Science.gov (United States)

    Hendriks, Henk F J

    2013-08-01

    In this paper, the nutrigenomics approach is discussed as a research tool to study the physiological effects of nutrition and consequently how nutrition affects health and disease (endpoints). Nutrigenomics is the study of the effects of foods and food constituents on gene expression; the analyses include analysis of mRNA, proteins and metabolites. Nutrigenomics may be useful in dealing with the challenges that nutrition research is facing; by integrating the description of numerous active genes and metabolic pathways stronger evidence and new biomarkers for subtle nutritional effects may be obtained. Also, a new definition of disease and health may be needed. The use of tests challenging homoeostasis is being proposed to help define health. Challenge tests may be able to demonstrate in a better way subtle beneficial effects of nutrition on health. The paper describes some basic concepts relevant to nutrition research as well as some of the possibilities that are offered by nutrigenomics technology. Some of its applications are described.

  14. Radiological endpoints relevant to ecological risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F. [Univ. of California, Lawrence Livermore National Lab., Livermore, CA (United States)

    1997-07-01

    Because of the potential risk from radiation due to the releases of radionuclides from anthropogenic activities, considerable research was performed to determine for humans the levels of dose received, their responses to the doses and mechanisms of action of radioactivity on living matter. More recently, there is an increased interest in the effects of radioactivity on non-human species. There are differences in approach between risk assessment for humans and ecosystems. For protection of humans, the focus is the individual and the endpoint of primary concern is cancer induction. For protection of ecosystems, the focus is on population stability and the endpoint of concern is reproductive success for organisms important ecologically and economically. For these organisms, information is needed on their responses to irradiation and the potential impact of the doses absorbed on their reproductive success. Considerable information is available on the effects of radiation on organisms from different phyla and types of ecosystems. Databases useful for assessing risk from exposures of populations to radioactivity are the effects of irradiation on mortality, fertility and sterility, the latter two of which are important components of reproductive success. Data on radiation effects on mortality are available both from acute and chronic irradiation. In relation to radiation effects, reproductive success for a given population is related to a number of characteristics of the species, including inherent radiosensitivity of reproductive tissues and early life stages, processes occurring during gametogenesis, reproductive strategy and exposure history. The available data on acute and chronic radiation doses is reviewed for invertebrates, fishes and mammals. The information reviewed indicates that wide ranges in responses with species can be expected. Parameters that most likely contribute to inherent radiosensitivity are discussed. (author)

  15. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates...... endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

  16. Effects of a performance and quality improvement intervention on the work environment in HIV-related care: a quasi-experimental evaluation in Zambia.

    Science.gov (United States)

    Bazant, Eva; Sarkar, Supriya; Banda, Joseph; Kanjipite, Webby; Reinhardt, Stephanie; Shasulwe, Hildah; Mulilo, Joyce Monica Chongo; Kim, Young Mi

    2014-12-20

    Human resource shortages and reforms in HIV-related care make it challenging for frontline health care providers in southern Africa to deliver high-quality services. At health facilities of the Zambian Defence Forces, a performance and quality improvement approach was implemented to improve HIV-related care and was evaluated in 2010/2011. Changes in providers' work environment and perceived quality of HIV-related care were assessed to complement data of provider performance. The intervention involved on-site training, supportive supervision, and action planning focusing on detailed service delivery standards. The quasi-experimental evaluation collected pre- and post-intervention data from eight intervention and comparison facilities matched on defence force branch and baseline client volume. Overall, 101 providers responded to a 24-item questionnaire on the work environment, covering topics of drugs, supplies, and equipment; training, feedback, and supervision; compensation; staffing; safety; fulfilment; and HIV services quality. In bivariate analysis and multivariate analyses, we assessed changes within each study group and between the two groups. In the bivariate analysis, the intervention group providers reported improvements in the work environment on adequacy of equipment, feeling safe from harm, confidence in clinical skills, and reduced isolation, while the comparison group reported worsening of the work environment on supplies, training, safety, and departmental morale.In the multivariate analysis, the intervention group's improvement and the comparison group's decline were significant on perceived adequacy of drugs, supplies, and equipment; constructive feedback received from supervisor and co-workers; and feeling safe from physical harm (all P improvement intervention implemented at Zambian Defence Forces' health facilities was associated with improvements in providers' perceptions of work environment consistent with the intervention's focus on

  17. HIV-related shame and health-related quality of life among older, HIV-positive adults.

    Science.gov (United States)

    Vincent, Wilson; Fang, Xindi; Calabrese, Sarah K; Heckman, Timothy G; Sikkema, Kathleen J; Hansen, Nathan B

    2017-06-01

    This study investigated how HIV-related shame is associated with health-related quality of life (HRQoL) in older people living with HIV (PLHIV). Structural equation modeling tested whether HIV-related shame was associated with three dimensions of HRQoL (physical, emotional, and social well-being) and whether there were significant indirect associations of HIV-related shame with the three HRQoL dimensions via depression and loneliness in a sample of 299 PLHIV ≥50 years old. Results showed that depression and loneliness were key mechanisms, with depression at least partially accounting for the association between HIV-related shame and both emotional and physical well-being, respectively, and loneliness accounting for the association between HIV-related shame and social well-being. HIV-related shame appears to be an important correlate of HRQoL in older PLHIV and may provide a promising leveraging point by which to improve HRQoL in older PLHIV.

  18. Latent variable indirect response modeling of categorical endpoints representing change from baseline.

    Science.gov (United States)

    Hu, Chuanpu; Xu, Zhenhua; Mendelsohn, Alan M; Zhou, Honghui

    2013-02-01

    Accurate exposure-response modeling is important in drug development. Methods are still evolving in the use of mechanistic, e.g., indirect response (IDR) models to relate discrete endpoints, mostly of the ordered categorical form, to placebo/co-medication effect and drug exposure. When the discrete endpoint is derived using change-from-baseline measurements, a mechanistic exposure-response modeling approach requires adjustment to maintain appropriate interpretation. This manuscript describes a new modeling method that integrates a latent-variable representation of IDR models with standard logistic regression. The new method also extends to general link functions that cover probit regression or continuous clinical endpoint modeling. Compared to an earlier latent variable approach that constrained the baseline probability of response to be 0, placebo effect parameters in the new model formulation are more readily interpretable and can be separately estimated from placebo data, thus allowing convenient and robust model estimation. A general inherent connection of some latent variable representations with baseline-normalized standard IDR models is derived. For describing clinical response endpoints, Type I and Type III IDR models are shown to be equivalent, therefore there are only three identifiable IDR models. This approach was applied to data from two phase III clinical trials of intravenously administered golimumab for the treatment of rheumatoid arthritis, where 20, 50, and 70% improvement in the American College of Rheumatology disease severity criteria were used as efficacy endpoints. Likelihood profiling and visual predictive checks showed reasonable parameter estimation precision and model performance.

  19. Persistent HIV-related stigma among an outpatient US clinic population.

    Science.gov (United States)

    Shacham, Enbal; Rosenburg, Neal; Önen, Nur F; Donovan, Michael F; Overton, E Turner

    2015-03-01

    Despite advancements in the public's understanding of HIV infection, felt stigma towards individuals living with HIV persists. Stigma has been associated with adverse health outcomes, including poor adherence to care, and increased participation in HIV transmission risk behaviours. We evaluated the level of felt stigma and its relationship to other psychosocial and medical factors among a sample of 201 individuals with HIV engaged in care. The overall mean stigma score, as measured by the Reece Stigma Scale, was 21.7 (SD 8.7). In univariate analysis, felt stigma scores were higher among women, African Americans, younger participants, and individuals with less education. Higher felt stigma scores were also found among individuals who reported having fair to poor overall health, moderate to severe symptoms of depression and anxiety, and those with a current diagnosis of alcohol dependence, generalised anxiety disorder, agoraphobia, pain disorder, and current smokers. Higher felt stigma scores were independently associated with individuals with anxiety symptoms. These analyses highlight that stigma persists among individuals with HIV and may play an important role in HIV care. The relationship between psychiatric disorders and psychosocial factors highlights an opportunity to develop interventions that will address these common comorbidities and reduce stigma. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. Using a clinic based creativity initiative to reduce HIV related stigma ...

    African Journals Online (AJOL)

    Background: Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a ...

  1. hiv-related renal disease - a clinical and practical approach in the ...

    African Journals Online (AJOL)

    In South Africa the majority of patients with HIVAN are black, although this may simply reflect the high prevalence of HIV in this population group in general. However, in a study from Cape Town Bates et 0/.' described 5 patients of mixed race in a cohort of 22 biopsy-proven HIVAN cases. Interestingly, patients with family ...

  2. HIV-Related Stigma Among African Immigrants Living with HIV/AIDS in USA

    OpenAIRE

    Emmanuel F. Koku

    2010-01-01

    Recent advances in the fight against HIV have increased the life expectancy of those infected. Despite these, a number of barriers such as stigma continue to affect HIV prevention and treatment. Although the body of work on HIV stigma is growing, there is a paucity of literature on the experiences of specific sub-groups such as African immigrants living with HIV. Drawing on in-depth interviews with a sample of these immigrants in the US, this study examines their experiences of HIV-related st...

  3. Gender differences in HIV-related self-reported knowledge, attitudes, and behaviors among college students.

    Science.gov (United States)

    Dekin, B

    1996-01-01

    A survey of 265 college students was conducted to determine HIV-related knowledge, attitudes, behavior, and perceived self-efficacy with regard to engaging in HIV-protective behaviors. A self-administered 52-item survey was completed by 265 college students (60% response rate). Resident advisors in college dormitories distributed the survey, returned anonymously. Data were analyzed using SPSS to identify differential responses by gender. Although HIV knowledge was high, perceived self-efficacy differed significantly by gender, with men describing themselves as less able to insist upon condom use (P planning; teenage pregnancy.

  4. Using verbal autopsy to track epidemic dynamics: the case of HIV-related mortality in South Africa

    Directory of Open Access Journals (Sweden)

    Mee Paul

    2011-08-01

    Full Text Available Abstract Background Verbal autopsy (VA has often been used for point estimates of cause-specific mortality, but seldom to characterize long-term changes in epidemic patterns. Monitoring emerging causes of death involves practitioners' developing perceptions of diseases and demands consistent methods and practices. Here we retrospectively analyze HIV-related mortality in South Africa, using physician and modeled interpretation. Methods Between 1992 and 2005, 94% of 6,153 deaths which occurred in the Agincourt subdistrict had VAs completed, and coded by two physicians and the InterVA model. The physician causes of death were consolidated into a single consensus underlying cause per case, with an additional physician arbitrating where different diagnoses persisted. HIV-related mortality rates and proportions of deaths coded as HIV-related by individual physicians, physician consensus, and the InterVA model were compared over time. Results Approximately 20% of deaths were HIV-related, ranging from early low levels to tenfold-higher later population rates (2.5 per 1,000 person-years. Rates were higher among children under 5 years and adults 20 to 64 years. Adult mortality shifted to older ages as the epidemic progressed, with a noticeable number of HIV-related deaths in the over-65 year age group latterly. Early InterVA results suggested slightly higher initial HIV-related mortality than physician consensus found. Overall, physician consensus and InterVA results characterized the epidemic very similarly. Individual physicians showed marked interobserver variation, with consensus findings generally reflecting slightly lower proportions of HIV-related deaths. Aggregated findings for first versus second physician did not differ appreciably. Conclusions VA effectively detected a very significant epidemic of HIV-related mortality. Using either physicians or InterVA gave closely comparable findings regarding the epidemic. The consistency between two

  5. Using verbal autopsy to track epidemic dynamics: the case of HIV-related mortality in South Africa.

    Science.gov (United States)

    Byass, Peter; Kahn, Kathleen; Fottrell, Edward; Mee, Paul; Collinson, Mark A; Tollman, Stephen M

    2011-08-05

    Verbal autopsy (VA) has often been used for point estimates of cause-specific mortality, but seldom to characterize long-term changes in epidemic patterns. Monitoring emerging causes of death involves practitioners' developing perceptions of diseases and demands consistent methods and practices. Here we retrospectively analyze HIV-related mortality in South Africa, using physician and modeled interpretation. Between 1992 and 2005, 94% of 6,153 deaths which occurred in the Agincourt subdistrict had VAs completed, and coded by two physicians and the InterVA model. The physician causes of death were consolidated into a single consensus underlying cause per case, with an additional physician arbitrating where different diagnoses persisted. HIV-related mortality rates and proportions of deaths coded as HIV-related by individual physicians, physician consensus, and the InterVA model were compared over time. Approximately 20% of deaths were HIV-related, ranging from early low levels to tenfold-higher later population rates (2.5 per 1,000 person-years). Rates were higher among children under 5 years and adults 20 to 64 years. Adult mortality shifted to older ages as the epidemic progressed, with a noticeable number of HIV-related deaths in the over-65 year age group latterly. Early InterVA results suggested slightly higher initial HIV-related mortality than physician consensus found. Overall, physician consensus and InterVA results characterized the epidemic very similarly. Individual physicians showed marked interobserver variation, with consensus findings generally reflecting slightly lower proportions of HIV-related deaths. Aggregated findings for first versus second physician did not differ appreciably. VA effectively detected a very significant epidemic of HIV-related mortality. Using either physicians or InterVA gave closely comparable findings regarding the epidemic. The consistency between two physician coders per case (from a pool of 14) suggests that double

  6. Predictors of HIV-related risk perception and PrEP acceptability among young adult female family planning patients.

    Science.gov (United States)

    Garfinkel, Danielle B; Alexander, Kamila A; McDonald-Mosley, Reagan; Willie, Tiara C; Decker, Michele R

    2017-06-01

    HIV pre-exposure prophylaxis (PrEP) presents new opportunities for HIV prevention. While women comprise approximately 20% of new HIV infections in the US, significant questions remain about how to most effectively facilitate PrEP uptake for this population. Family planning clinics are a dominant source of health care for young women and support an estimated 4.5 million women annually. We explore characteristics associated with HIV risk perception and PrEP acceptability among young adult women seeking reproductive health services in a high-prevalence setting. A cross-sectional, clinic-based survey was conducted with women ages 18-35 (n = 146) seeking health care at two family planning clinics in the greater Baltimore, Maryland area, from January to April 2014. An estimated 22% of women reported being worried about HIV risk, and 60% reported they would consider taking a pill daily to prevent HIV. In adjusted models, HIV-related worry was associated with having no college education, being single or dating more than one person, practicing consistent condom use during vaginal sex, and having ever traded sex. PrEP acceptability was significantly associated with being Black (71% vs. 49%, AOR 2.23, CI: 1.89-2.64) and having ever traded sex (83% vs. 58%, AOR 4.94, CI: 2.00-12.22). For women with a history of intimate partner violence (IPV), PrEP acceptability was significantly lower (57% vs. 62%, AOR .71, CI: .59-.85) relative to their non-abused counterparts. Results suggest that family planning clinics may be a natural setting for PrEP discussion and roll-out. They should be considered in the context of integrating HIV prevention with reproductive health services. Women with a trauma history may need additional support for implementing HIV prevention in the form of PrEP.

  7. [Validation of the Spanish version of the HIV Related Fatigue Scale and application in people with hepatitis C].

    Science.gov (United States)

    García-Sierra, Rosa María; Feijoo-Cid, Maria; Font-Canals, Roser; Varoucha-Azcarate, Ana Cristina; Bernal-Balada, Rosó; López-Parra, Maria; Caballero-Sáez, Iolanda; Pérez-Bernal, Mercè

    2015-01-01

    To validate the American fatigue scale HIV-Related Fatigue Scale (HRFS) and present the Spanish version called Integrated Fatigue Assessment Scale to assess fatigue in HCV and co-infected patients. Psychometric study with cross-sectional design was used. The HRFS was translated into Spanish using the back-translation method-later to be validated. Participants completed the questionnaire adapted to a self-report form, as well as a sociodemographic questionnaire. The reliability and validity of the Spanish version was evaluated. A total of 7 public service hospitals and two prisons in Catalonia participated in the evaluation. The sample consisted of 122 subjects selected by consecutive sampling in the fourth week of treatment of hepatitis C with combination therapy or triple therapy. The Cronbach alpha for the total scale was 0.958. Content Validity Index (I-CVI) varied from 0.5 to 1. Validity Scale Content-level (S-CVI) was 0.85. Pearson correlations between the three dimensions were between 0.49 and 0.68. The process followed for the cultural adaptation and validation shows that the Spanish version of the HRFS) is a valid and reliable instrument that can be used in clinical practice and in the investigation of fatigue in patients with hepatitis C. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. HIV-related risk perception among female sex workers in Nigeria.

    Science.gov (United States)

    Ankomah, Augustine; Omoregie, Godpower; Akinyemi, Zacch; Anyanti, Jennifer; Ladipo, Olaronke; Adebayo, Samson

    2011-01-01

    Over one-third of sex workers in Nigeria are infected with human immunodeficiency virus (HIV), yet there is a lack of understanding of sex workers' own perception of sexual risk-taking. Applying the theory of cognitive dissonance, this paper examined the personal HIV risk perception of brothel-based sex workers. The study is based on 24 focus group discussions held among brothel-based sex workers in four geographically and culturally dispersed cities in Nigeria. It was found that sex workers underestimated their risk of infection and rationalized, defended, or justified their behaviors, a typical psychological response to worry, threat, and anxiety arising from the apparent discrepancies between beliefs and behaviors. To reduce dissonance, many sex workers had a strong belief in fatalism, predestination, and faith-based invulnerability to HIV infection. Many believed that one will not die of acquired immune deficiency syndrome if it is not ordained by God. The sex workers also had a high level of HIV-related stigma. From these findings, most sex workers considered risk reduction and in particular condom use as far beyond their control or even unnecessary, as a result of their strong beliefs in fatalism and predestination. Therefore, one critical area of intervention is the need to assist sex workers to develop accurate means of assessing their personal vulnerability and self-appraisal of HIV-related risk.

  9. Re-thinking HIV-Related Stigma in Health Care Settings: A Qualitative Study.

    Science.gov (United States)

    Gagnon, Marilou

    2015-01-01

    People living with HIV (PLWH) continue to endure stigma and discrimination in the context of health care. This paper presents the findings of a qualitative study designed to (a) describe stigmatizing and discriminatory practices in health care settings, and (b) explore both symbolic and structural stigma from the perspectives of PLWH. For the purpose of this qualitative study, 21 semi-structured in-depth interviews were conducted in the province of Quebec, Canada. The data were analyzed following the principles of thematic analysis. During analysis, three themes were identified, and relations between these themes were delineated to reflect the experiences of participants. The findings suggest that HIV-related stigma in health care settings is episodic in nature. The findings also suggest that HIV-related stigma is experienced through interactions with health care providers (symbolic stigma) and, finally, that it is applied systematically to manage risk in the context of health care (structural stigma). Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  10. A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

    Science.gov (United States)

    Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

    2017-03-01

    It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

  11. Self-care behaviors and activities for managing HIV-related anxiety.

    Science.gov (United States)

    Kemppainen, Jeanne K; Wantland, Dean; Voss, Joachim; Nicholas, Patrice; Kirksey, Kenn M; Corless, Inge B; Willard, Suzanne; Holzemer, William L; Robinson, Linda; Hamilton, Mary Jane; Sefcik, Elizabeth; Eller, Lucille Sanzero; Huang, Emily; Arudo, John; Moezzi, Shahnaz; Rivero-Mendez, Marta; Rosa, Maria; Human, Sarie; Cuca, Yvette; Lindgren, Terri; Portillo, Carmen J; Maryland, Mary

    2012-01-01

    The goal of this study was to identify the baseline prevalence and effectiveness of anxiety self-management strategies in a convenience sample of persons living with HIV (PLWH; n = 343) in the United States, Puerto Rico, Kenya, and South Africa who reported HIV-related anxiety symptoms. Relationships between demographics and anxiety characteristics were determined, as was the effectiveness of self-care activities/behaviors to reduce anxiety. We found that the use of anxiety self-management strategies varied by gender and that ratings of effectiveness varied by country. Highest anxiety intensity scores were found in participants who were taking antiretroviral medications and who had undetectable viral loads. Forty-five percent of the persons with a diagnosis of AIDS reported anxiety symptoms. As HIV increases in areas of the world where self-care is the primary approach to managing HIV, additional research will be needed to address the effectiveness of cross-cultural differences in strategies for self-managing HIV-related anxiety. Copyright © 2012 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  12. Transgender women and HIV-related health disparities: falling off the HIV treatment cascade.

    Science.gov (United States)

    Kalichman, Seth C; Hernandez, Dominica; Finneran, Stephanie; Price, Devon; Driver, Redd

    2017-10-01

    Background Transgender women living with HIV infection experience poorer health outcomes across the HIV continuum of care. While disparities are well established, their underlying mechanisms are not well understood. This study examined the HIV continuum of care (also known as the HIV treatment cascade), including linkage and engagement in care and health status among transgender women and cisgender women and cisgender men living with HIV. Case-control matching was applied to a cohort of 1101 people living with HIV; 70 transgender women living with HIV were matched on years since testing HIV positive with cisgender women and cisgender men. Participants provided measures indicative of the HIV treatment cascade that included linkage and engagement in care, receiving and adhering to antiretroviral therapy (ART), and HIV viral suppression. Common correlates of HIV-related health status: depression symptoms, HIV-related stress, alcohol and drug use, healthcare conspiracy beliefs, medical mistrust, emotional social support and tangible social support, were also assessed. Transgender women were significantly less likely to receive ART, were less adherent to ART and had poorer HIV viral suppression than cisgender persons. Multivariable models demonstrated that health disparities were predicted by transgender women having poorer tangible social support over and above the other correlates of health outcomes. Tangible support is amenable by interventions such as building and strengthening supportive networks and paraprofessional services. Socially supportive interventions should be considered critical in efforts to decrease HIV health disparities among transgender women.

  13. Social Networking Technology Use and Engagement in HIV Related Risk and Protective Behaviors among Homeless Youth

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-01-01

    Preliminary studies with homeless youth find surprisingly pervasive social media use and suggest youths’ online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical first step in intervention development is gaining greater understanding of how homeless youth use social media especially as it relates to whom they connect to and around what topics. Given the salience of Social Networking Sites in the lives of these otherwise difficult to reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N=1046) were recruited through three drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether or not they engage in risk or protective behaviors. Implications for interventions and further research are discussed. PMID:27337044

  14. [HIV-related symptoms in patients with HIV infection enrolled in an HIV case management program in Taiwan].

    Science.gov (United States)

    Yeh, Mei-Ling; Liu, Hsiao-Ying; Ko, Wen-Chien; Lee, Hsin-Chun; Ko, Nai-Ying

    2009-02-01

    Patients with HIV (human immunodeficiency virus) experience multiple signs and symptoms that accompany the progress of HIV-related diseases. HIV-related symptoms are associated with side effects and HAART (highly active antiretroviral therapy) complications. The purposes of this study were to estimate the frequency and intensity of HIV-related signs and symptoms in patients with HIV infection and to explore relationships between HIV-related symptoms and the HAART regimen. Data on a total of 172 HIV-positive patients enrolled in an HIV case management program were analyzed for this study. Participants experienced an average of 9.73+/-7.27 symptoms, with fatigue, dry mouth and weakness the most frequently reported. Average mean symptom intensity among participants was 13.24+/-11.48. Insomnia, depression and disorientation were the most severe symptoms. No differences were recorded between HIV-related symptoms and disease progression. Fatigue intensity showed significant differences between NRTI (nucleoside reverse transcriptase inhibitors), +NNRTI (non-nucleoside reverse transcriptase inhibitors) and NRTI+PI (protease inhibitors) based regimens (p=.03). In addition, cluster symptoms of confusion/distress among participants without HAART had a significantly higher mean intensity than those with HAART (t=2.0, df=1, p=.04). Our study indicated that symptom management for fatigue and early detection of psychological distress is needed to improve quality of life for people living with HIV/AIDS.

  15. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)

    DEFF Research Database (Denmark)

    Vestbo, J; Anderson, W; Coxson, H O

    2008-01-01

    . Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) is a 3-yr longitudinal study with four specific aims: 1) definition of clinically relevant COPD subtypes; 2) identification of parameters that predict disease progression in these subtypes; 3) examination of biomarkers...

  16. Days with severe symptoms: an additional efficacy endpoint in immunotherapy trials.

    Science.gov (United States)

    Durham, S R; Birk, A O; Andersen, J S

    2011-01-01

    In immunotherapy trials, primary and secondary endpoints often focus on average symptom and medication scores during the pollen season or on days with low symptoms and low medication use. Thus, there is a need for endpoints describing the treatment effect on the most troublesome days in the pollen season. A possible additional efficacy endpoint, days with severe symptoms during the pollen season, was investigated using data from a multicentre, double-blind, randomized, placebo-controlled trial of the SQ-standardized grass allergy immunotherapy tablet (AIT) (Grazax, Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Hørsholm, Denmark). The trial included 634 subjects (N(Grass AIT) = 316; N(Placebo) = 318) with grass pollen-induced rhinoconjunctivitis. Six different definitions of a day with severe symptoms were suggested. The number of days with severe symptoms was analysed and odds ratios were calculated. The number and percentage of days with severe symptoms differed between definitions, but overall the analysis of days with severe symptoms showed consistent results (odds ratios: 2.0-3.4) for the different definitions. All definitions showed a reduced risk of having days with severe symptoms in the grass AIT group when compared to the placebo group. Days with severe symptoms during the pollen season is a relevant additional efficacy endpoint, which can be used in immunotherapy trials to support the clinical interpretation of commonly used efficacy endpoints. © 2010 John Wiley & Sons A/S.

  17. A systematic comparison of recurrent event models for application to composite endpoints.

    Science.gov (United States)

    Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

    2018-01-04

    Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

  18. Hippeastrum hybridum anthocyanins as indicators of endpoint in ...

    African Journals Online (AJOL)

    Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong ...

  19. HIV-related risk perception among female sex workers in Nigeria

    Directory of Open Access Journals (Sweden)

    Ankomah A

    2011-07-01

    Full Text Available Augustine Ankomah1, Godpower Omoregie1, Zacch Akinyemi2, Jennifer Anyanti1, Olaronke Ladipo1, Samson Adebayo11Society for Family Health, Abuja, Nigeria; 2Population Services International, Kigali, RwandaBackground: Over one-third of sex workers in Nigeria are infected with human immunodeficiency virus (HIV, yet there is a lack of understanding of sex workers’ own perception of sexual risk-taking. Applying the theory of cognitive dissonance, this paper examined the personal HIV risk perception of brothel-based sex workers.Methods: The study is based on 24 focus group discussions held among brothel-based sex workers in four geographically and culturally dispersed cities in Nigeria.Results: It was found that sex workers underestimated their risk of infection and rationalized, defended, or justified their behaviors, a typical psychological response to worry, threat, and anxiety arising from the apparent discrepancies between beliefs and behaviors. To reduce dissonance, many sex workers had a strong belief in fatalism, predestination, and faith-based invulnerability to HIV infection. Many believed that one will not die of acquired immune deficiency syndrome if it is not ordained by God. The sex workers also had a high level of HIV-related stigma.Conclusion: From these findings, most sex workers considered risk reduction and in particular condom use as far beyond their control or even unnecessary, as a result of their strong beliefs in fatalism and predestination. Therefore, one critical area of intervention is the need to assist sex workers to develop accurate means of assessing their personal vulnerability and self-appraisal of HIV-related risk.Keywords: female sex workers, cognitive dissonance, risk perception, risky behavior, focus group discussions, Nigeria

  20. HIV-Related Risk Behaviors Among Labor Migrants, Their Wives and the General Population in Nepal.

    Science.gov (United States)

    Thapa, Subash; Thapa, Deependra Kaji; Buve, Anne; Hannes, Karin; Nepal, Chiranjibi; Mathei, Catharina

    2017-04-01

    Nepalese labor migrants and their wives are considered as at-risk populations for HIV infection. There may be a risk of HIV transmission from the labor migrant and their wives to the general population due to HIV-related risk behaviors, but so far empirical evidence to support this hypothesis is scarce. Therefore, this study was conducted to compare HIV-related risk behaviors between labor migrants, their wives, and males and females from the general population in the far-western region of Nepal. This was a cross-sectional study, in which structured face-to-face interviews were conducted with 261 male labor migrants, 262 wives of labor migrants, 123 males and 122 females from the general population. We found that the proportion of the labor migrants and their wives reporting having had extramarital sex in the previous year did not differ significantly with the males (11.9 vs. 13.4 %, p value 0.752) and females (2.0 vs. 1.7 %, p value 0.127) from the general population. However, the labor migrants compared with the males from the general population were 1.51 times and the wives of labor migrants compared with the females from the general population were 2.37 times more likely to have been tested for HIV. Both the males from the general population and the labor migrants are equally engaged in unprotected extramarital sex. Therefore, it is recommended that the prevention programs, including access to condoms and HIV testing, should be scaled up targeting a broader range of individuals in the far-western region of Nepal.

  1. Persisting stigma reduces the utilisation of HIV-related care and support services in Viet Nam

    Directory of Open Access Journals (Sweden)

    Thanh Duong Cong

    2012-11-01

    Full Text Available Abstract Background Seeking and utilisation of HIV prevention, treatment, care, and support services for people living with HIV is often hampered by HIV-related stigma. The study aimed to explore the perceptions and experiences regarding treatment, care, and support amongst people living with HIV in Viet Nam, where the HIV epidemic is concentrated among injecting drug users, sex workers, and men who have sex with men. Methods In-depth interviews and focus group discussions were conducted during September 2007 in 6 districts in Hai Phong with a very high HIV prevalence among injecting drug users. The information obtained was analysed and merged within topic areas. Illustrative quotes were selected. Results Stigma and discrimination against people living with HIV in the community and healthcare settings was commonly reported, and substantially hampered the seeking and the utilisation of HIV-related services. The informants related the high level of stigma to the way the national HIV preventive campaigns played on fear, by employing a “scare tactic” mainly focusing on drug users and sex workers, who were defined as “social evils” in the anti-drug and anti-prostitution policy. There was a strong exclusion effect caused by the stigma, with serious implications, such as loss of job opportunities and isolation. The support and care provided by family members was experienced as vital for the spirit and hope for the future among people living with HIV. Conclusions A comprehensive care and support programme is needed. The very high levels of stigma experienced seem largely to have been created by an HIV preventive scare tactic closely linked to the “social evil“ approach in the national policy on drug and prostitution. In order to reduce the stigma and create more effective interventions, this tactic will have to be replaced with approaches that create better legal and policy environments for drug users and sex workers.

  2. Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

    Science.gov (United States)

    Angel, Juana; Steele, A Duncan; Franco, Manuel A

    2014-01-01

    Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

  3. Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Menke, Ricarda A L; Agosta, Federica; Grosskreutz, Julian; Filippi, Massimo; Turner, Martin R

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further multicenter research is now needed to establish their validity as therapeutic outcome measures.

  4. Ecosystem services as assessment endpoints for ecological risk assessment.

    Science.gov (United States)

    Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G

    2016-07-01

    Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag

  5. Beliefs Contributing to HIV-related Stigma in African and Afro-Caribbean Communities in the Netherlands

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Kesteren, N.M.C. van; Shiripinda, I.; Pryor, J.B.; Bruin, M. de; Schaalma, H.P.

    2012-01-01

    Thirty years after the first diagnosis, people living with HIV (PLWH) around the world continue to report stigmatizing experiences. In this study, beliefs contributing to HIV-related stigma in African and Afro-Caribbean diaspora communities and their cultural context were explored through

  6. HIV-related stigma in African and Afro-Caribbean communities in the Netherlands: manifestations, consequences and coping.

    Science.gov (United States)

    Stutterheim, Sarah E; Bos, Arjan E R; Shiripinda, Iris; de Bruin, Marijn; Pryor, John B; Schaalma, Herman P

    2012-01-01

    HIV-related stigma in African and Afro-Caribbean diaspora communities in the Netherlands was investigated. Interviews with HIV-positive and HIV-negative community members demonstrated that HIV-related stigma manifests as social distance, physical distance, words and silence. The psychological consequences of HIV-related stigma among those diagnosed with HIV reported were emotional pain, sadness, loneliness, anger, frustration and internalised stigma. The social consequences included decreased social network size, limited social support and social isolation, and resulted from not only enacted stigma but also self-imposed social withdrawal. Also, poor treatment adherence was a health-related consequence. People living with HIV employed both problem-focused and emotion-focused coping strategies to mitigate the negative consequences of stigma. Problem-focused coping strategies included selective disclosure, disengagement, affiliating with similar others, seeking social support and, to a lesser extent, activism. Emotion-focused strategies included distraction, positive reappraisal, religious coping, external attributions, disidentification and acceptance. HIV-related stigma clearly permeates African and Afro-Caribbean communities in the Netherlands, and should be targeted for intervention.

  7. Adapting the Information-Motivation-Behavioral Skills Model: Predicting HIV-Related Sexual Risk among Sexual Minority Youth

    Science.gov (United States)

    Fisher, Colleen M.

    2012-01-01

    Young sexual minority males are among those at highest risk for HIV infection, yet we know relatively little about the impact of sexual identity development on HIV risk. This study used cross-sectional data to investigate factors associated with HIV-related sexual risk among a sample of sexual minority males (n = 156), ages 14 to 21 years, using…

  8. The analysis of terminal endpoint events in stepped wedge designs.

    Science.gov (United States)

    Zhan, Zhuozhao; de Bock, Geertruida H; Wiggers, Theo; van den Heuvel, Edwin

    2016-10-30

    The stepped wedge design is a unique clinical trial design that allows for a sequential introduction of an intervention. However, the statistical analysis is unclear when this design is applied in survival data. The time-dependent introduction of the intervention in combination with terminal endpoints and interval censoring makes the analysis more complicated. In this paper, a time-on-study scale discrete survival model was constructed. Simulations were conducted primarily to study the performance of our model for different settings of the stepped wedge design. Secondary, we compared our approach to continuous Cox proportional hazard model. The results show that the discrete survival model estimates the intervention effects unbiasedly. If the length of the censoring interval is increased, the precision of the estimates is decreased. Without left truncation and late entry, the number of steps improves the precision of the estimates, whereas in combination of left truncation and late entry, the number of steps decreases the precision. Given the same number of participants and clusters, a parallel group design has higher precision than a stepped wedge design. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa.

    Science.gov (United States)

    Hargreaves, James R; Stangl, Anne; Bond, Virginia; Hoddinott, Graeme; Krishnaratne, Shari; Mathema, Hlengani; Moyo, Maureen; Viljoen, Lario; Brady, Laura; Sievwright, Kirsty; Horn, Lyn; Sabapathy, Kalpana; Ayles, Helen; Beyers, Nulda; Bock, Peter; Fidler, Sarah; Griffith, Sam; Seeley, Janet; Hayes, Richard

    2016-12-01

    Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. HIV-related stigma may impede the

  10. HIV-related stigma among an urban sample of persons living with HIV at risk for dropping out of HIV-oriented primary medical care.

    Science.gov (United States)

    Relf, Michael V; Rollins, Kate V

    2015-01-01

    HIV-related stigma is one of the greatest barriers to preventing and ending the HIV epidemic. The purpose of our study was to examine HIV-related stigma among urban adults voluntarily seeking HIV-oriented primary medical care and at risk for dropping out after enrolling. The baseline cross-sectional analysis of perceived HIV-related stigma upon enrolling in care examined the level of HIV-related stigma and its sub-domains: personalized, disclosure, negative self-image, and public attitudes. Our study also identified precursors of HIV-related stigma and associated outcomes. HIV-related stigma continues to be a significant problem for persons living with HIV; those perceiving higher levels of HIV-related stigma reported a poorer quality of life, both physically and mentally. The relationship between HIV-related stigma and mental health was closely connected in our sample. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  11. Automatic streak endpoint localization from the cornerness metric

    Science.gov (United States)

    Sease, Brad; Flewelling, Brien; Black, Jonathan

    2017-05-01

    Streaked point sources are a common occurrence when imaging unresolved space objects from both ground- and space-based platforms. Effective localization of streak endpoints is a key component of traditional techniques in space situational awareness related to orbit estimation and attitude determination. To further that goal, this paper derives a general detection and localization method for streak endpoints based on the cornerness metric. Corners detection involves searching an image for strong bi-directional gradients. These locations typically correspond to robust structural features in an image. In the case of unresolved imagery, regions with a high cornerness score correspond directly to the endpoints of streaks. This paper explores three approaches for global extraction of streak endpoints and applies them to an attitude and rate estimation routine.

  12. Accurate measurement method for tube's endpoints based on machine vision

    Science.gov (United States)

    Liu, Shaoli; Jin, Peng; Liu, Jianhua; Wang, Xiao; Sun, Peng

    2017-01-01

    Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube's endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube's endpoints based on machine vision is proposed. First, reflected light on tube's surface can be removed by using photometric linearization. Then, based on the optimization model for the tube's endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube's endpoint are obtained. To confirm the feasibility, 11 tubes are processed to remove the reflected light and then the endpoint's positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 mm. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube's endpoints without any surface treatment or any tools and can realize on line measurement.

  13. Workplace and HIV-related sexual behaviours and perceptions among female migrant workers.

    Science.gov (United States)

    Yang, H; Li, X; Stanton, B; Fang, X; Lin, D; Mao, R; Liu, H; Chen, X; Severson, R

    2005-10-01

    Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment establishments (e.g. restaurants, stalls, domestic service, factories, etc.). About 10% of women in the entertainment establishments reported having sold sex, 30% having multiple sexual partners and 40% having sex with men with multiple sexual partners. The rate of consistent condom use was less than 15%. They also tended to have a higher level of perceptions of both peer risk involvement and positive expectancy of risk behaviours, and lower perceptions of severity of STDs and HIV. For women who were not sexually experienced, those working in 'stalls' or 'domestic service' tended to perceive higher peer risk involvement, less severity of HIV infection, and less effectiveness of protective behaviour. The occupational pattern of sexual risk behaviours and perceptions observed in the current study indicates employment conditions are associated with HIV risk. Intervention strategies should be tailored to address occupational-related factors.

  14. Loneliness and HIV-related stigma explain depression among older HIV-positive adults.

    Science.gov (United States)

    Grov, Christian; Golub, Sarit A; Parsons, Jeffrey T; Brennan, Mark; Karpiak, Stephen E

    2010-05-01

    Advances in the treatment of HIV have resulted in a large growing population of older adults with HIV. These aging adults face added social, psychological, and physical challenges associated with the aging process. Correlations between depression, loneliness, health, and HIV/AIDS-related stigma have been studied, but there is little evaluation of these associations among HIV-positive adults over the age of 50. Data for these analyses were taken from the Research on Older Adults with HIV study of 914 New York City-based HIV-positive men and women over the age of 50. In total, 39.1% of participants exhibited symptoms of major depression (CES-D > 23). Multivariate modeling successfully explained 42% of the variance in depression which was significantly related to increased HIV-associated stigma, increased loneliness, decreased cognitive functioning, reduced levels of energy, and being younger. These data underscore the need for service providers and researchers to assert more aggressive and innovative efforts to resolve both psychosocial and physical health issues that characterize the graying of the AIDS epidemic in the USA. Data suggest that focusing efforts to reduce HIV-related stigma and loneliness may have lasting effects in reducing major depressive symptoms and improving perceived health.

  15. Qualitative study of HIV related stigma and discrimination: What women say in Iran.

    Science.gov (United States)

    Oskouie, Fatemeh; Kashefi, Farzaneh; Rafii, Forough; Gouya, Mohammad Mehdi

    2017-07-01

    HIV-related stigma is a major social problem of people living with HIV. Stigma against these people, especially women, interferes with the prevention, diagnosis and treatment of HIV. This study examined the experiences of HIV infected women who were stigmatized, as well as the strategies used to tackle the issue. Twenty-five women living with HIV were examined using in-depth, semi-structured interviews. The data obtained was analyzed using content analysis method in MAXQDA10. The finding of this study was classified into four themes: fear, shame, rejection by family or friends and feelings of frustration. The participant strategies adopted to the perceived stigma and discrimination included isolation, nondisclosure, and loss of follow-up. HIV in women has different social interposition. It is necessary to intervene, so as to alleviate the effect of stigma on HIV infected women, in order that they gain the ability to accomplish wellness, increase life span and improve quality of life. Nurses, midwives and other professionals need to be involved to ensure public policy in providing supportive environments, and decrease stigma.

  16. Women of Color Reflect on HIV-Related Stigma through PhotoVoice.

    Science.gov (United States)

    Davtyan, Mariam; Farmer, Shu; Brown, Brandon; Sami, Mojgan; Frederick, Toni

    2016-01-01

    HIV-related stigma affects people living with HIV (PLWH), especially in communities of color. In our study, African American and Latina/Hispanic women living with HIV (WLWH) described experiences of stigma through PhotoVoice, a community-based participatory method of documentary photography. Ten WLWH from Los Angeles documented stigma experiences through photographs for up to 5 weeks and discussed their images during a focus group or semi-structured individual interview. Qualitative interpretive phenomenological analysis of participant narratives and photographs revealed lack of education and cultural myths as the main triggers of the stigma our participants faced. Stigma was experienced in health care settings, and participants identified depression, fear of intimate relationships, and nondisclosure of HIV status as its consequences. Social support and faith were noted as key coping mechanisms. WLWH recommended involving PLWH and public health officials in stigma reduction campaigns and youth education. PhotoVoice was perceived as a useful tool for education and self-improvement. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  17. HIV-related knowledge and perceptions by academic major: Implications for university interventions

    Directory of Open Access Journals (Sweden)

    Matthew Lee Smith

    2014-03-01

    Full Text Available Most universities offer human sexuality courses, although they are not required for graduation. While students in health-related majors may receive sexuality education in formal settings, majority of college students never receive formal sexual health or HIV/AIDS-related education, which may lead to elevated engagement in high-risk sexual behaviors. This study examines perceived knowledge about HIV/AIDS, perceived risk, and perceived consequences among college students by two distinct classifications of academic majors. Data were collected from 510 college students. Binary and multinomial logistic regressions were performed to compare HIV-related covariates by academic major category. Limited differences were observed by Science, Technology, Engineering, and Mathematics (STEM categorization. Relative to health and kinesiology (HK majors, those who self-reported being completely knowledgeable about HIV were less likely to be physical sciences, math, engineering, business (PMEB [OR=0.41, P=0.047] or education, humanities, and social sciences (EHS majors [OR=0.25, P=0.004]. PMEB majors were less likely to report behavioral factors as a risk for contracting HIV [OR=0.86, P=0.004] and perceived acquiring HIV would be more detrimental to their quality of life [OR=2.14, P=0.012], but less detrimental to their mental wellbeing [OR=0.58, P=0.042]. Findings can inform college-wide campaigns and interventions to raise HIV/AIDS awareness and improve college health.

  18. Toward Automating HIV Identification: Machine Learning for Rapid Identification of HIV-Related Social Media Data.

    Science.gov (United States)

    Young, Sean D; Yu, Wenchao; Wang, Wei

    2017-02-01

    "Social big data" from technologies such as social media, wearable devices, and online searches continue to grow and can be used as tools for HIV research. Although researchers can uncover patterns and insights associated with HIV trends and transmission, the review process is time consuming and resource intensive. Machine learning methods derived from computer science might be used to assist HIV domain experts by learning how to rapidly and accurately identify patterns associated with HIV from a large set of social data. Using an existing social media data set that was associated with HIV and coded by an HIV domain expert, we tested whether 4 commonly used machine learning methods could learn the patterns associated with HIV risk behavior. We used the 10-fold cross-validation method to examine the speed and accuracy of these models in applying that knowledge to detect HIV content in social media data. Logistic regression and random forest resulted in the highest accuracy in detecting HIV-related social data (85.3%), whereas the Ridge Regression Classifier resulted in the lowest accuracy. Logistic regression yielded the fastest processing time (16.98 seconds). Machine learning can enable social big data to become a new and important tool in HIV research, helping to create a new field of "digital HIV epidemiology." If a domain expert can identify patterns in social data associated with HIV risk or HIV transmission, machine learning models could quickly and accurately learn those associations and identify potential HIV patterns in large social data sets.

  19. Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

    Science.gov (United States)

    Netski, Dale M; Mao, Qing; Ray, Stuart C; Klein, Robert S

    2008-10-01

    We tested the hypothesis that HIV-related immunosuppression alters the host-hepatitis C virus (HCV) interaction, resulting in fewer amino acid-changing substitutions in HCV viral variants. Higher HCV RNA levels in persons coinfected with HIV compared with HCV infection alone suggest increased viral replication. If this increase is dependent on decreased immune selective pressure, then a reduced rate of nucleotide changes resulting in amino acid replacements (nonsynonymous changes, dN) would be expected. We investigated HCV envelope sequences over time in 79 persons with chronic HCV infection who were HIV negative (group 1) or HIV positive with (group 3) or without (group 2) severe immunodeficiency. We amplified a 1026-nt region of the HCV genome, which encodes a portion of the envelope glycoproteins E1 and E2, including hypervariable region-1 for direct sequence analysis. The overall divergence between paired sequences, dS, dN, and dN/dS, all showed no significant differences among the 3 groups. By measuring nucleotide substitutions in HCV sequences over time, we found no significant differences in the genetic divergence between HCV-monoinfected control subjects and HIV/HCV-coinfected subjects with various levels of immunodeficiency as measured by CD4+ T-cell counts.

  20. Female sex workers' empowerment strategies amid HIV-related socioeconomic vulnerabilities in Cameroon.

    Science.gov (United States)

    Cange, Charles W; LeBreton, Matthew; Saylors, Karen; Billong, Serge; Tamoufe, Ubald; Fokam, Pamella; Baral, Stefan

    2017-10-01

    Research has consistently demonstrated that female sex workers use a variety of empowerment strategies to protect one another and their families. This study examines the strategies Cameroonian sex workers employ to do so. In-depth interviews and focus-group discussions were conducted with 100 sex workers. Coded texts were analysed for recurring themes. Sex workers reported being concerned with physical violence and sexual assault and demands from authorities for bribes to avoid fines and/or imprisonment. Women described strategies such as 'looking out for' each other when faced with security threats. Many reported staying in sex work to provide for their children through education and other circumstances to allow them to lead a better life. Sex worker mothers reported not using condoms when clients offered higher pay, or with intimate partners, even when they understood the risk of HIV transmission to themselves. Concern for their children's quality of life took precedence over HIV-related risks, even when sex workers were the children's primary carers. A sex worker empowerment programme with a focus on family-oriented services could offer an effective and novel approach to increasing coverage of HIV prevention, treatment and care in Cameroon.

  1. Fear of Foreigners: HIV-related restrictions on entry, stay, and residence.

    Science.gov (United States)

    Amon, Joseph J; Todrys, Katherine Wiltenburg

    2008-12-16

    Among the earliest and the most enduring responses to the HIV/AIDS epidemic has been the imposition by governments of entry, stay, and residence restrictions for non-nationals living with HIV and AIDS. Sixty-six of the 186 countries in the world for which data are available currently have some form of restriction in place. Although international human rights law allows for discrimination in the face of public health considerations, such discrimination must be the least intrusive measure required to effectively address the public health concern. HIV-related travel restrictions, by contrast, not only do not protect public health, but result in deleterious effects both at the societal level - negatively impacting HIV prevention and treatment efforts - and at the individual level, affecting, in particular, labor migrants, refugee candidates, students, and short-term travelers. Governments should repeal these laws and policies, and instead devote legislative attention and national resources to comprehensive HIV prevention, care, and treatment programmes serving citizens and non-citizens alike.

  2. Global Reduction in HIV-related Maternal Mortality: ART as a Key Strategy

    Directory of Open Access Journals (Sweden)

    Hamisu M. Salihu, MD, PhD

    2015-12-01

    Full Text Available Dr. Holtz and colleagues present a synthesis of evidence from published studies over the previous decade on the collective impact of HIV-targeted interventions on maternal mortality. Amongst an assortment of interventions [that include antiretroviral therapy (ART, micronutrients (multivitamins, vitamin A and selenium, and antibiotics], only ART reduced maternal mortality among HIV-infected pregnant and post-partum mothers. These findings have fundamental and global strategic implications. They are also timely since they provide the evidence that ART reduces HIV-related maternal mortality, and by further enhancing access to ART in HIV-challenged and poor regions of the world, significant improvement in maternal morbidity and mortality indices could be attained. The paper bears good tidings and sound scientific proof that the financial investment made globally by government and non-governmental organizations and agencies to reduce the global burden of HIV/AIDS primarily by making ART more accessible to regions of the world most affected by the epidemic is beginning to show beneficial effects not only in terms of numerical reductions in the rates of new cases of HIV/AIDS among women, but also in maternal mortality levels.

  3. HIV-related risk behaviors among male inmates of Tehran, Iran

    Directory of Open Access Journals (Sweden)

    SeyedAhmad SeyedAlinaghi

    2016-05-01

    Full Text Available Objective: To investigate the frequencies and types of HIV-related risk behavior among inmates of Tehran, Iran. Methods: We used active case finding to assess the prevalence of HIV high risk behaviors. The research was conducted on male prisoners in the Great Tehran Prison from October 2013 to May 2014. Results: Two thousand and fifty (19.5% from 10 492 prisoners who were admitted to “quarantine” of the prison participated in HIV testing and counseling. Of 2 050 inmates, our results showed that sexual encounters were the most prevalent risky behavior (89.6% reported by the prisoners, followed by tattooing (34.7% and injection drug use (24.2%. Conclusions: Although the previous studies reported that the main leading cause of acquiring HIV infection in Iranian prisons was injecting drug use, the prevalence of injecting drug use was less than the prevalence of unsafe sexual relationships and tattooing in the present research among the inmates of Tehran.

  4. Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus document

    NARCIS (Netherlands)

    A.P. Kappetein (Arie Pieter); S.J. Head (Stuart); P. Généreux (Philippe); N. Piazza (Nicolo); N.M. van Mieghem (Nicolas); E.H. Blackstone (Eugene); T.G. Brott (Thomas); D.J. Cohen (David J.); D.E. Cutlip (Donald); G.A. van Es (Gerrit Anne); R.T. Hahn (Rebecca); A.J. Kirtane (Ajay); M. Krucoff (Mitchell); S. Kodali (Susheel); M.J. Mack (Michael); R. Mehran (Roxana); J. Rodés-Cabau (Josep); P. Vranckx (Pascal); J.G. Webb (John); S.W. Windecker (Stephan); P.W.J.C. Serruys (Patrick); M.B. Leon (Martin)

    2012-01-01

    textabstractObjectives: The aim of the current Valvular Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)- clinical endpoints to make them more suitable to the present and future needs of clinical trials.

  5. Drop-out from cardiovascular magnetic resonance in a randomized controlled trial of ST-elevation myocardial infarction does not cause selection bias on endpoints

    DEFF Research Database (Denmark)

    Laursen, Peter Nørkjær; Holmvang, L.; Kelbæk, H.

    2017-01-01

    Background: The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before...... a higher incidence of cardiovascular risk factors at baseline, a worse clinical risk profile upon admission. However, no significant difference was observed in the clinical endpoints between the groups....

  6. Autoregressive transitional ordinal model to test for treatment effect in neurological trials with complex endpoints

    Directory of Open Access Journals (Sweden)

    Lorenzo G. Tanadini

    2016-11-01

    Full Text Available Abstract Background A number of potential therapeutic approaches for neurological disorders have failed to provide convincing evidence of efficacy, prompting pharmaceutical and health companies to discontinue their involvement in drug development. Limitations in the statistical analysis of complex endpoints have very likely had a negative impact on the translational process. Methods We propose a transitional ordinal model with an autoregressive component to overcome previous limitations in the analysis of Upper Extremity Motor Scores, a relevant endpoint in the field of Spinal Cord Injury. Statistical power and clinical interpretation of estimated treatment effects of the proposed model were compared to routinely employed approaches in a large simulation study of two-arm randomized clinical trials. A revisitation of a key historical trial provides further comparison between the different analysis approaches. Results The proposed model outperformed all other approaches in virtually all simulation settings, achieving on average 14 % higher statistical power than the respective second-best performing approach (range: -1 %, +34 %. Only the transitional model allows treatment effect estimates to be interpreted as conditional odds ratios, providing clear interpretation and visualization. Conclusion The proposed model takes into account the complex ordinal nature of the endpoint under investigation and explicitly accounts for relevant prognostic factors such as lesion level and baseline information. Superior statistical power, combined with clear clinical interpretation of estimated treatment effects and widespread availability in commercial software, are strong arguments for clinicians and trial scientists to adopt, and further extend, the proposed approach.

  7. HIV Among Indigenous peoples: A Review of the Literature on HIV-Related Behaviour Since the Beginning of the Epidemic.

    Science.gov (United States)

    Negin, Joel; Aspin, Clive; Gadsden, Thomas; Reading, Charlotte

    2015-09-01

    From the early days of the HIV epidemic, Indigenous peoples were identified as a population group that experiences social and economic determinants-including colonialism and racism-that increase exposure to HIV. There are now substantial disparities in HIV rates between Indigenous and non-Indigenous peoples in some countries. We conducted a comprehensive literature review to assess the evidence on HIV-related behaviors and determinants in four countries-Australia, Canada, New Zealand and the United States-in which Indigenous peoples share important features of colonization and marginalization. We identified 107 articles over more than 20 years. The review highlights the determinants of HIV-related behaviors including domestic violence, stigma and discrimination, and injecting drug use. Many of the factors associated with HIV risk also contribute to mistrust of health services, which in turn contributes to poor HIV and health outcomes among Indigenous peoples.

  8. HIV-Related Stigma and Overlapping Stigmas Towards People Living With HIV Among Health Care Trainees in Canada.

    Science.gov (United States)

    Wagner, Anne C; Girard, Todd; McShane, Kelly E; Margolese, Shari; Hart, Trevor A

    2017-08-01

    HIV continues to be a stigmatized disease, despite significant advances in care and concerted effort to reduce discrimination, stereotypes, and prejudice. Living with HIV is often associated with a multitude of overlapping and intersecting experiences which can, in and of themselves, also be stigmatized, and which may exacerbate HIV-related stigma. The consequences of these stigmatizing experiences are particularly impactful when the stigmatizing individual is a health care provider, as this can influence access to and quality of care. The current study empirically investigates a model of overlapping stigmas (homophobia, racism, sexism, stigma against injection drug use and stigma against sex work) potentially held by health care provider trainees in Canada to determine how these constructs overlap and intersect, and to assess whether HIV-related stigma may have unique attributes. Understanding overlapping stigmas can help inform targeted, stigma-informed training for health care trainees in order to provide effective, compassionate care for people living with HIV.

  9. Sex inequalities in HIV-related practices in the Brazilian population aged 15 to 64 years old, 2008

    Directory of Open Access Journals (Sweden)

    Ana Roberta Pati Pascom

    2011-01-01

    Full Text Available The objective of this study is to analyze gender differences in HIV-related practices in the Brazilian population. A national survey was carried out in 2008 with a sample size of 8,000 individuals aged 15-64 years old. The sampling was stratified by macro geographical region and urban/rural areas. Logistic regression models were used to investigate the main predictors of consistent condom use. The results showed that women have less sexy, start sexual life later than men, have fewer casual sexual partners, but use condom less frequently than men. On the other hand, the coverage of HIV testing is significantly greater among women. Significant differences by gender were seen in all HIV-related risky practices. The greater vulnerability was always associated with women, with exception of HIV testing. The low proportion of condom use in infidelity situations was a problem for box sexes and deserves special consideration when developing prevention strategies.

  10. HIV-Related Medical Admissions to a South African District Hospital Remain Frequent Despite Effective Antiretroviral Therapy Scale-Up

    Science.gov (United States)

    Meintjes, Graeme; Kerkhoff, Andrew D.; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Van Wyk, Gavin; Blumenthal, Liz; Nicol, Mark P.; Lawn, Stephen D.

    2015-01-01

    Abstract The public sector scale-up of antiretroviral therapy (ART) in South Africa commenced in 2004. We aimed to describe the hospital-level disease burden and factors contributing to morbidity and mortality among hospitalized HIV-positive patients in the era of widespread ART availability. Between June 2012 and October 2013, unselected patients admitted to medical wards at a public sector district hospital in Cape Town were enrolled in this cross-sectional study with prospective follow-up. HIV testing was systematically offered and HIV-infected patients were systematically screened for TB. The spectrum of admission diagnoses among HIV-positive patients was documented, vital status at 90 and 180 days ascertained and factors independently associated with death determined. Among 1018 medical admissions, HIV status was ascertained in 99.5%: 60.1% (n = 609) were HIV-positive and 96.1% (n = 585) were enrolled. Of these, 84.4% were aware of their HIV-positive status before admission. ART status was naive in 35.7%, current in 45.0%, and interrupted in 19.3%. The most frequent primary clinical diagnoses were newly diagnosed TB (n = 196, 33.5%), other bacterial infection (n = 100, 17.1%), and acquired immunodeficiency syndrome (AIDS)-defining illnesses other than TB (n = 64, 10.9%). By 90 days follow-up, 175 (29.9%) required readmission and 78 (13.3%) died. Commonest causes of death were TB (37.2%) and other AIDS-defining illnesses (24.4%). Independent predictors of mortality were AIDS-defining illnesses other than TB, low hemoglobin, and impaired renal function. HIV still accounts for nearly two-thirds of medical admissions in this South African hospital and is associated with high mortality. Strategies to improve linkage to care, ART adherence/retention and TB prevention are key to reducing HIV-related hospitalizations in this setting. PMID:26683950

  11. Nonvolitional sex and HIV-related sexual risk behaviours among MSM in the United States.

    Science.gov (United States)

    Nasrullah, Muazzam; Oraka, Emeka; Chavez, Pollyanna R; Valverde, Eduardo; Dinenno, Elizabeth

    2015-08-24

    We estimated the prevalence of lifetime nonvolitional sex (NVS) among MSM by demographic characteristics, and characterized its association with HIV-related sexual risk behaviours among MSM in the United States. The National Survey of Family Growth (NSFG) is a nationally representative cross-sectional survey of the United States. NSFG data from recent cycles 2002, and 2006-2010 were weighted and analysed for men aged 18-44 years who reported ever having anal or oral intercourse with another male. Associations of lifetime NVS (forced sex by men or women) and age of first NVS experience (sexual risk behaviour outcomes in the past 12 months (i.e. sex with two or more male sex partners; exchanged sex for money or drugs; sex with IDU; sex with HIV-positive person; sex with two or more female sex partners) were assessed using adjusted prevalence ratios (aPR). An estimated 3 226 872 or 5.8% of men aged 18-44 years were identified as MSM with 24.6% of them reporting ever experiencing NVS. MSM reporting NVS at age 18 years or older were more likely to have had sex with an IDU [aPR = 4.40; 95% confidence interval (95% CI) 1.78-10.88] and exchanged sex for money or drugs (aPR = 2.52; 95% CI 1.17-5.43) in the past 12 months compared with those not reporting NVS. NVS for MSM less than 18 years of age was associated with exchanging sex for money or drugs. Effective interventions to raise awareness of NVS among MSM and to offer support for MSM who have experienced NVS are needed.

  12. HIV-related discrimination among grade six students in nine Southern African countries.

    Science.gov (United States)

    Maughan-Brown, Brendan; Spaull, Nicholas

    2014-01-01

    HIV-related stigmatisation and discrimination by young children towards their peers have important consequences at the individual level and for our response to the epidemic, yet research on this area is limited. We used nationally representative data to examine discrimination of HIV-positive children by grade six students (n = 39,664) across nine countries in Southern Africa: Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Zambia and Zimbabwe. Descriptive statistics are used to compare discrimination by country, gender, geographic location and socioeconomic status. Multivariate logistic regression is employed to assess potential determinants of discrimination. The levels and determinants of discrimination varied significantly between the nine countries. While one in ten students in Botswana, Malawi, South Africa and Swaziland would "avoid or shun" an HIV positive friend, the proportions in Lesotho, Mozambique, Zambia and Zimbabwe were twice as high (approximately 20%). A large proportion of students believed that HIV positive children should not be allowed to continue to attend school, particularly in Zambia (33%), Lesotho (37%) and Zimbabwe (42%). The corresponding figures for Malawi and Swaziland were significantly lower at 13% and 12% respectively. Small differences were found by gender. Children from rural areas and poorer schools were much more likely to discriminate than those from urban areas and wealthier schools. Importantly, we identified factors consistently associated with discrimination across the region: students with greater exposure to HIV information, better general HIV knowledge and fewer misconceptions about transmission of HIV via casual contact were less likely to report discrimination. Our study points toward the need for early interventions (grade six or before) to reduce stigma and discrimination among children, especially in schools situated in rural areas and poorer communities. In particular, interventions

  13. Multi-endpoint biological monitoring in combined, carcinogenic occupational exposures.

    Science.gov (United States)

    Szendi, Katalin; Hornyák, László; Varga, Csaba

    2017-10-01

    We aimed to develop a relevant multi-endpoint biomonitoring system by studying different genotoxicity biomarkers in complex carcinogenic exposures under occupational situations. Altogether 109 workers were followed in five different workplaces. The combined carcinogenic exposures were monitored in the urine and peripheral blood samples using Ames mutagenicity test and cytogenetic analyzes. The different genotoxicity endpoints studied showed different results in the same carcinogenic exposure situations. The urinary mutagenicity tests provided more information and proved to be more sensitive compared to the cytogenetic tests in the majority of cases. In complex exposures multistep biomonitoring panel should be applied, because the exact mechanisms of the combination of single exposing agents are not known. Such a panel should involve monitoring different endpoints, e.g. point mutations, chromosomal mutations. A relatively affordable and rapid testing panel was developed using validated tests as Ames and cytogenetic assays, but its practical use should be confirmed by further investigations.

  14. Comparing sensitivity of ecotoxicological effect endpoints between laboratory and field

    DEFF Research Database (Denmark)

    Selck, H.; Riemann, B.; Christoffersen, K.

    2002-01-01

    Extrapolating toxicant effects with a fixed application factor (AF) approach or one of the species sensitivity distribution (SSD) models presumes that toxicant effects on single, individual-level endpoints reflect effects at the ecosystem level. Measured effect concentrations on plankton from mul...

  15. Combined functional and anatomical diagnostic endpoints for assessing arteriovenous fistula dysfunction.

    Science.gov (United States)

    Rajabi-Jaghargh, Ehsan; Banerjee, Rupak K

    2015-02-06

    Failure of arteriovenous fistulas (AVF) to mature and thrombosis in matured fistulas have been the major causes of morbidity and mortality in hemodialysis patients. Stenosis, which occurs due to adverse remodeling in AVFs, is one of the major underlying factors under both scenarios. Early diagnosis of a stenosis in an AVF can provide an opportunity to intervene in a timely manner for either assisting the maturation process or avoiding the thrombosis. The goal of surveillance strategies was to supplement the clinical evaluation (i.e., physical examination) of the AVF for better and earlier diagnosis of a developing stenosis. Surveillance strategies were mainly based on measurement of functional hemodynamic endpoints, including blood flow (Qa) to the vascular access and venous access pressure (VAP). As the changes in arterial pressure (MAP) affects the level of VAP, the ratio of VAP to MAP (VAPR = VAP/MAP) was used for diagnosis. A Qa 0.55 is considered sign of significant stenosis, which requires immediate intervention. However, due to the complex nature of AVFs, the surveillance strategies have failed to consistently detect stenosis under different scenarios. VAPR has been primarily developed to detect outflow stenosis in arteriovenous grafts, and it hasn't been successful in accurate diagnosis of outflow lesions in AVFs. Similarly, AVFs can maintain relatively high blood flow despite the presence of a significant outflow stenosis and thus, Qa has been found to be a better predictor of only inflow lesions. Similar shortcomings have been reported in the detection of functional severity of coronary stenosis using diagnostic endpoints that were based on either flow or pressure. This limitation has been associated with the fact that both pressure and flow change in the presence of a stenosis and thus, hemodynamic diagnostic endpoints that employ only one of these parameters are inherently prone to inaccuracies. Recent attempts have resulted in development of new

  16. HIV-Related Stigma and HIV Prevention Uptake Among Young Men Who Have Sex with Men and Transgender Women in Thailand.

    Science.gov (United States)

    Logie, Carmen H; Newman, Peter A; Weaver, James; Roungkraphon, Surachet; Tepjan, Suchon

    2016-02-01

    HIV-related stigma is a pervasive structural driver of HIV. With an HIV epidemic among young men who have sex with men (MSM) and transgender women (TG) in Thailand characterized as explosive, we conducted a cross-sectional survey among MSM and TG aged 18-30 years. From April-August 2013, participants recruited using venue-based sampling from gay entertainment sites and community-based organizations completed a tablet-assisted survey interview in Thai language. We conducted multiple logistic regression to assess correlations between HIV-related stigma (felt-normative, vicarious domains) and socio-demographic variables, HIV vulnerabilities (gay entertainment employment, sex work, forced sex history), and HIV prevention uptake (condom use, HIV testing, rectal microbicide acceptability). Among participants (n = 408), 54% identified as gay, 25% transgender, and 21% heterosexual. Two-thirds (65.7%) were employed at gay entertainment venues, 67.0% had more than three male partners (past month), 55.6% had been paid for sex, and 4.5% were HIV-positive. One-fifth (21.3%) reported forced sex. Most participants reported experiencing felt-normative and vicarious HIV-related stigma. Adjusting for socio-demographics, participants with higher total HIV-related stigma scores had significantly lower odds of HIV testing and rectal microbicide acceptability, and higher odds of having experienced forced sex. Both vicarious and felt-normative dimensions of HIV-related stigma were inversely associated with HIV testing and rectal microbicide acceptability. Our findings suggest that HIV-related stigma harms the health of HIV-negative MSM and TG at high risk for HIV infection. HIV-related interventions and research among young MSM and TG in Thailand should address multiple dimensions of HIV-related stigma as a correlate of risk and a barrier to accessing prevention.

  17. HIV-related stigma and symptoms of post-traumatic stress disorder and depression in HIV-infected individuals: does social support play a mediating or moderating role?

    Science.gov (United States)

    Breet, Elsie; Kagee, Ashraf; Seedat, Soraya

    2014-01-01

    HIV stigma plays a major role in the etiology of psychological distress among persons living with HIV, but may be ameliorated by social support. This cross-sectional study examined whether social support mediates or moderates the relationship between HIV stigma and psychological symptoms. We recruited a convenience sample of 210 individuals living with HIV in three peri-urban communities in the Western Cape, South Africa. People living with HIV and AIDS (PLWHA) completed self-report questionnaires that assessed HIV-related stigma, social support, post-traumatic stress disorder (PTSD) and depression. Product-term regression analyses showed that social support played a mediating role in the relationship between HIV-related stigma and symptoms of PTSD (not depression). Social support did not, however, moderate the relationship between HIV-related stigma and PTSD or depression. The results indicate that perceived HIV-related stigma may decrease PLWHA's perceived level of social support, which in turn may increase PTSD symptoms. Moreover, these findings suggest that despite the protective role of social support, there are other factors that affect the relationship between HIV-related stigma and mental health that hinder the buffering role of social support in this relationship. These findings may have implications for designing and implementing interventions that increase perceived social support and decrease perceived HIV-related stigma, which in turn may decrease symptoms of PTSD among PLWHA.

  18. Implementation of cellulomonas cholesterol oxidase for total serum cholesterol determination by the endpoint method.

    Science.gov (United States)

    Srisawasdi, Pornpen; Chaichanajarernkul, Upsorn; Teerakranjana, Narumon; Kroll, Martin H

    2008-01-01

    Cellulomonas has been shown to be a good source of cholesterol oxidase in addition to Streptomyces for serum cholesterol determination by the endpoint method, inexpensive in cost, and showing excellent performance. For clinical use, we have assessed the reliability of Cellulomonas reagent for cholesterol determination. We constructed the user-defined endpoint methods on three automated analyzers. The analytical performances (linearity, precision, recovery, interference, stability, and comparison with the standardized method) of Cellulomonas cholesterol reagents were evaluated and compared to those of Streptomyces reagents. Linearity (18.1-23.3 mmol/L) and stability of reagents (6-11 weeks) depended on the analyzers being used. The average within-run and between-day % coefficients of variation (CVs) ranged from 1.44 to 2.45 and 1.98 to 2.99, respectively, and were within National Cholesterol Education Program analytical criteria (Cellulomonas enzyme is analytically reliable when used for serum cholesterol determination by the endpoint method. Its analytical performance is equivalent to Streptomyces enzymes and meets the analytical goals. It has an advantage over the other enzymes in that it does not ship in the frozen state. (c) 2008 Wiley-Liss, Inc.

  19. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  20. Infant formula and neurocognitive outcomes: impact of study end-point selection.

    Science.gov (United States)

    Sun, H; Como, P G; Downey, L C; Murphy, D; Ariagno, R L; Rodriguez, W

    2015-10-01

    Assessing validity and reliability of end points used in docosahexanoic and arachidonic acids (DHA and ARA) infant formula supplementation trials as an example for addressing the impact of end-point selection and critical need for well-defined, reliable and validated clinical outcome assessments for neurocognitive assessment in neonates and infants. We searched eight electronic databases and reviewed all randomized, controlled human trials using DHA/ARA supplements with neurodevelopment clinical outcomes. We systematically evaluated the validity and reliability of end-point measures based on the criteria for studying nutritional additives recommended by the Institute of Medicine, criteria described in the Food and Drug Administration guidance for clinical outcome assessment, development and literature review. We identified 29 articles that met the selection criteria. The end points that were used for neurodevelopment measures in 23 out of 29 original short-term studies included the Bayley Scale of Infant Development (BSID)-I and -II (n=12), Brunet-Lezine test (n=2), videotape infant's movements (n=1), record time to milestones including sitting, crawling, standing and walking (n=1), problem-solving test (n=2), brainstem auditory-evoked potential (n=1), Touwen examination (n=1), Fagan test of infant intelligence (n=2) and visual habituation protocol (n=1). None of these end points have a long-term predictive property for neurocognitive assessment. Compared with standard infant formula, the beneficial effects of DHA/ARA supplementation on neurodevelopment were reported in 2 out of 12 studies using BSID vs 8 out of 11 studies using other end-point measures. In addition, 6 out of 29 long-term follow-up studies used the end points including Stanford-Binet IQ test (n=1), Wechsler Preschool and Primary Scale of Intelligence (n=4) and Bracken Basic Concept Scale (n=1), which are generally scales of intellectual ability and typically do not change substantively in the short

  1. Concurrent evaluation of general, immune, and genetic toxicity endpoints as part of an integrated testing strategy.

    Science.gov (United States)

    Schisler, Melissa R; Sura, Radhakrishna; Visconti, Nicolo R; Sosinski, Lindsay K; Murphy, Lynea A; LeBaron, Matthew J; Boverhof, Darrell R

    2014-08-01

    Integrated testing strategies involve the assessment of multiple endpoints within a single toxicity study and represent an important approach for reducing animal use and streamlining testing. The present study evaluated the ability to combine general, immune, and genetic toxicity endpoints into a single study. Specifically, this study evaluated the impact of sheep red blood cell (SRBC) immunization, as part of the T-cell dependent antibody response (TDAR) assay, on organ weights, micronuclei (MN) formation (bone marrow and peripheral blood), and the Comet assay response in the liver of female F344/DuCrl rats treated with cyclophosphamide (CP) a known immunosuppressive chemical and genotoxicant. For the TDAR assay, treatment with CP resulted in a dose-dependent decrease in the antibody response with a suppression of greater than 95% at the high dose. Injection with SRBC had no impact on evaluated organ weights, histopathology, hematology, and clinical chemistry parameters. Analysis of MN formation in bone marrow and peripheral blood revealed a dose-dependent increase in response to CP treatment. Injection with SRBC had no impact on the level of MN in control animals and did not alter the dose response of CP. There was a slight increase in liver DNA damage in response to CP as measured by the Comet assay; however, injection with SRBCs did not alter this endpoint. Overall these data provide strong support for the concurrent assessment of general, immune, and genetic toxicology endpoints within a single study as part of an integrated testing strategy approach. © 2014 Wiley Periodicals, Inc.

  2. Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

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    Gori E

    2016-11-01

    -α across the three groups. Regarding plasma lipoproteins, HDL-c levels were reduced in HIV ART-naïve (P=0.002 and ART-receiving (P=0.015 subjects compared to HIV-uninfected subjects. Similarly, TC levels were lower in the HIV-infected than in the HIV-uninfected group regardless of whether the patients were undergoing ART or not (P<0.001. IL-10 levels correlated with TC levels in the HIV-uninfected group but not in the HIV-infected groups. Levels of HDL-c were reduced, while IL-10 plasma concentrations were elevated in HIV-infected individuals. A correlation observed in HIV-uninfected individuals between anti-inflammatory cytokine IL-10 and TC was lost in HIV-infected individuals. Clinical significance of these differences needs to be ascertained with respect to HIV-related CVD risk. Keywords: HIV, inflammation, cytokines, antiretroviral therapy, cardiovascular disease risk

  3. HIV-related stigma and psychological distress: the harmful effects of specific stigma manifestations in various social settings.

    Science.gov (United States)

    Stutterheim, Sarah E; Pryor, John B; Bos, Arjan E R; Hoogendijk, Robert; Muris, Peter; Schaalma, Herman P

    2009-11-13

    Recent research has shown that experiences of stigmatization have an adverse impact on the psychological well being of people living with HIV/AIDS (PLWHA). Most studies investigating this relationship employ an aggregate measure of stigma. Although this approach provides useful information about the psychological implications of HIV-related stigma in general, it neglects to acknowledge the possibility that some manifestations in specific settings may be psychologically more detrimental than others. The present study examines which specific stigma experiences are most strongly related to psychological distress across a number of social settings. A cross-sectional survey was administered to 667 PLWHA in the Netherlands. We examined participants' experiences of 11 manifestations of HIV-related stigma in six social settings. Linear regression analyses were conducted to determine which setting-specific manifestations best predict psychological distress after controlling for marital status, education and health status. Three manifestations in family settings, namely receiving advice to conceal one's status, being avoided and being treated with exaggerated kindness, and one manifestation in healthcare settings, namely awkward social interaction, best predicted psychological distress in PLWHA. Manifestations of HIV-related stigma vary according to setting. Certain manifestations in specific social settings impact the psychological well being of PLWHA more than others. In this study, certain experiences of stigmatization with PLWHA's families and in healthcare settings were more strongly related to psychological distress than experiences occurring in other social settings. These findings suggest that stigma reduction interventions focusing on these influential settings may benefit the psychological well being of PLWHA.

  4. Differences in HIV-related behaviors at Lugufu refugee camp and surrounding host villages, Tanzania

    Directory of Open Access Journals (Sweden)

    Mbaruku Godfrey

    2008-10-01

    Full Text Available Abstract Background An HIV behavioral surveillance survey was undertaken in November 2005 at Lugufu refugee camp and surrounding host villages, located near western Tanzania's border with the Democratic Republic of Congo (DRC. Methods The sample size was 1,743 persons based on cluster survey methodology. All members of selected households between 15–49 years old were eligible respondents. Questions included HIV-related behaviors, population displacement, mobility, networking and forced sex. Data was analyzed using Stata to measure differences in proportions (chi-square and differences in means (t-test between gender, age groups, and settlement location for variables of interest. Results Study results reflect the complexity of factors that may promote or inhibit HIV transmission in conflict-affected and displaced populations. Within this setting, factors that may increase the risk of HIV infections among refugees compared to the population in surrounding villages include young age of sexual initiation among males (15.9 years vs. 19.8 years, p = .000, high-risk sex partners in the 15–24 year age group (40% vs. 21%, χ2 33.83, p = .000, limited access to income (16% vs. 51% χ2 222.94, p = .000, and the vulnerability of refugee women, especially widowed, divorced and never-married women, to transactional sex (married vs. never married, divorced, widowed: for 15–24 age group, 4% and 18% respectively, χ2 8.07, p = .004; for 25–49 age group, 4% and 23% respectively, χ2 21.46, p = .000. A majority of both refugee and host village respondents who experienced forced sex in the past 12 months identified their partner as perpetrator (64% camp and 87% in villages. Although restrictions on movements in and out of the camp exist, there was regular interaction between communities. Condom use was found to be below 50%, and expanded population networks may also increase opportunities for HIV transmission. Availability of refugee health services may be

  5. Validation of an HIV-related stigma scale among health care providers in a resource-poor Ethiopian setting

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    Feyissa GT

    2012-03-01

    Full Text Available Garumma Tolu Feyissa1, Lakew Abebe1, Eshetu Girma1, Mirkuzie Woldie21Department of Health Education and Behavioral Sciences, 2Department of Health Services Management, Jimma University, Jimma, EthiopiaBackground: Stigma and discrimination (SAD against people living with human immunodeficiency virus (HIV are barriers affecting effective responses to HIV. Understanding the causes and extent of SAD requires the use of a psychometrically reliable and valid scale. The objective of this study was to validate an HIV-related stigma scale among health care providers in a resource-poor setting.Methods: A cross-sectional validation study was conducted in 18 health care institutions in southwest Ethiopia, from March 14, 2011 to April 14, 2011. A total of 255 health care providers responded to questionnaires asking about sociodemographic characteristics, HIV knowledge, perceived institutional support (PIS and HIV-related SAD. Exploratory factor analysis (EFA with principal component extraction and varimax with Kaiser normalization rotation were employed to develop scales for SAD. Eigenvalues greater than 1 were used as a criterion of extraction. Items with item-factor loadings less than 0.4 and items loading onto more than one factor were dropped. The convergent validity of the scales was tested by assessing the association with HIV knowledge, PIS, training on topics related to SAD, educational status, HIV case load, presence of an antiretroviral therapy (ART service in the health care facility, and perceived religiosity.Results: Seven factors emerged from the four dimensions of SAD during the EFA. The factor loadings of the items ranged from 0.58 to 0.93. Cronbach's alphas of the scales ranged from 0.80 to 0.95. An in-depth knowledge of HIV, perceptions of institutional support, attendance of training on topics related to SAD, degree or higher education levels, high HIV case loads, the availability of ART in the health care facility and claiming oneself as

  6. Roberge-Weiss endpoint in Nf=2 QCD

    Science.gov (United States)

    Bonati, Claudio; Cossu, Guido; D'Elia, Massimo; Sanfilippo, Francesco

    2011-03-01

    We present the results of extensive simulations regarding the critical behavior at the endpoint of the Roberge-Weiss transition for Nf=2 QCD. We confirm early evidence, presented in Ref. [M. D’Elia and F. Sanfilippo, Phys. Rev. DPRVDAQ1550-799810.1103/PhysRevD.80.111501 80, 111501(R) (2009).], according to which the Roberge-Weiss endpoint is first order in the limit of large or small quark masses, and second order for intermediate masses. A systematic study of the transition strength as a function of the quark mass in the first order regions, permits us to estimate the tricritical values of the quark mass separating the second order region from the first order ones.

  7. Internal bremsstrahlung endpoint energy of {sup 54}Mn

    Energy Technology Data Exchange (ETDEWEB)

    Hindi, M. M. [Physics Department, Tennessee Technological University, Cookeville, Tennessee 38505 (United States); Larimer, R.-M. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Norman, E. B. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Rech, G. A. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2000-05-01

    For {sup 54}Mn there is a discrepancy between the Q{sub EC} obtained from the endpoint energy of the internal bremsstrahlung (IB) spectrum which accompanies the electron capture decay (Q{sub EC}=1353{+-}8 keV) and that obtained from the accepted mass differences (Q{sub EC}=1377{+-}1 keV). This Q value is needed to deduce the partial-half life of the astrophysically interesting {beta}{sup -} decay of {sup 54}Mn from the recently measured {beta}{sup +} partial half-life. To resolve this discrepancy, we have remeasured the endpoint energy of the IB spectrum, by recording coincidences between the IB and the 835-keV {gamma} ray, both detected in Compton-suppressed Ge detectors. The Q{sub EC} we deduce is 1379{+-}8 keV, in agreement with the accepted mass differences. (c) 2000 The American Physical Society.

  8. Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint.

    Science.gov (United States)

    Tang, Zhongwen

    2015-01-01

    An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

  9. Associations between HIV-related stigma, racial discrimination, gender discrimination, and depression among HIV-positive African, Caribbean, and Black women in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen; James, Llana; Tharao, Wangari; Loutfy, Mona

    2013-02-01

    Abstract African, Caribbean, and Black (ACB) women are greatly overrepresented in new HIV infections in comparison with Canada's general population. Social and structural factors such as HIV-related stigma, gender discrimination, and racial discrimination converge to increase vulnerability to HIV infection among ACB women by reducing access to HIV prevention services. Stigma and discrimination also present barriers to treatment, care, and support and may contribute to mental health problems. We administered a cross-sectional survey to HIV-positive ACB women (n=173) across Ontario in order to examine the relationships between HIV-related stigma, gender discrimination, racial discrimination, and depression. One-third of participants reported moderate/severe depression scores using the Beck Depression Inventory Fast-Screen guidelines. Hierarchical block regression, moderation, and mediation analyses were conducted to measure associations between independent (HIV-related stigma, gender discrimination, racial discrimination), moderator/mediator (social support, resilient coping), and dependent (depression) variables. Findings included: (1) HIV-related stigma was associated with increased depression; (2) resilient coping was associated with reduced depression but did not moderate the influence of HIV-related stigma on depression; and (3) the effects of HIV-related stigma on depression were partially mediated through resilient coping. HIV-related stigma, gender discrimination, and racial discrimination were significantly correlated with one another and with depression, highlighting the salience of examining multiple intersecting forms of stigma. Generalizability of findings may be limited due to nonrandom sampling. Findings emphasize the importance of multi-component interventions, including building resilient coping skills, mental health promotion and assessment, and stigma reduction programs.

  10. Dimensions of sexual orientation and HIV-related risk among adolescent females: evidence from a statewide survey.

    Science.gov (United States)

    Goodenow, Carol; Szalacha, Laura A; Robin, Leah E; Westheimer, Kim

    2008-06-01

    We examined the relationship of 2 dimensions of sexual orientation--sexual identity and sex of partners--with self-reported behaviors and experiences to identify factors that may place adolescent females at risk of HIV/AIDS. We gathered data on sexually experienced female high school students from 4 waves of a population-based survey. We used logistic regression analyses to investigate the association between their sexual identity (3666 heterosexual; 184 lesbian, gay, or bisexual; 113 not sure) and sex of partners (3714 male only, 79 female only, and 180 both males and females) with HIV-related risk behaviors. Self-defined sexual identity was often inconsistent with sex of sexual partners. Sexual identities other than heterosexual and having same-sex partners (either exclusively or in addition to male partners) were associated with high rates of several HIV-related risk behaviors. Coerced sexual contact was significantly associated with every risk outcome. AIDS education in school predicted lower HIV risk on 4 of 6 indicators. Programs to prevent HIV infection among adolescent females should take into account the complexity of sexual orientation and should address the needs and behaviors of sexual-minority youths.

  11. Association Between Enacted Stigma and HIV-Related Risk Behavior Among MSM, National HIV Behavioral Surveillance System, 2011.

    Science.gov (United States)

    Balaji, Alexandra B; Bowles, Kristina E; Hess, Kristen L; Smith, Justin C; Paz-Bailey, Gabriela

    2017-01-01

    MSM bear a disproportionate burden of the HIV epidemic. Enacted stigma (overt negative actions) against sexual minorities may play an important role in increasing HIV risk among this population. Using data from the 2011 National HIV Behavioral Surveillance system, MSM cycle, we examined the independent associations between three measures of enacted stigma (verbal harassment, discrimination, physical assault) and engagement in each of four HIV-related risk behaviors as outcomes: condomless anal intercourse (CAI) at last sex with a male partner of HIV discordant or unknown status and, in the past 12 months, CAI with a male partner, ≥4 male sex partners, and exchange sex. Of 9819 MSM, 32% experienced verbal harassment in the past 12 months, 23% experienced discrimination, and 8% experienced physical assault. Discordant CAI at last sex with a male partner was associated with previous discrimination and physical assault. Past 12 month CAI with a male partner, ≥4 male sex partners, and exchange sex were each associated with verbal harassment, discrimination, and physical assault. These findings indicate that a sizable proportion of MSM report occurrences of past 12 month enacted stigma and suggest that these experiences may be associated with HIV-related risk behavior. Addressing stigma towards sexual minorities must involve an integrated, multi-faceted approach, including interventions at the individual, community, and societal level.

  12. Social Networking Technology Use and Engagement in HIV-Related Risk and Protective Behaviors Among Homeless Youth.

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-07-01

    Preliminary studies with homeless youth have found surprisingly pervasive social media use and suggest that youth's online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical 1st step in intervention development is gaining greater understanding of how homeless youth use social media, especially as it relates to who they connect to and around what topics. Given the salience of social networking sites in the lives of these otherwise difficult-to-reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N = 1,046) were recruited through 3 drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether youth engage in risk or protective behaviors. Implications for interventions and further research are discussed.

  13. Choice of futility boundaries for group sequential designs with two endpoints

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    Svenja Schüler

    2017-08-01

    Full Text Available Abstract Background In clinical trials, the opportunity for an early stop during an interim analysis (either for efficacy or for futility may relevantly save time and financial resources. This is especially important, if the planning assumptions required for power calculation are based on a low level of evidence. For example, when including two primary endpoints in the confirmatory analysis, the power of the trial depends on the effects of both endpoints and on their correlation. Assessing the feasibility of such a trial is therefore difficult, as the number of parameter assumptions to be correctly specified is large. For this reason, so-called ‘group sequential designs’ are of particular importance in this setting. Whereas the choice of adequate boundaries to stop a trial early for efficacy has been broadly discussed in the literature, the choice of optimal futility boundaries has not been investigated so far, although this may have serious consequences with respect to performance characteristics. Methods In this work, we propose a general method to construct ‘optimal’ futility boundaries according to predefined criteria. Further, we present three different group sequential designs for two endpoints applying these futility boundaries. Our methods are illustrated by a real clinical trial example and by Monte-Carlo simulations. Results By construction, the provided method of choosing futility boundaries maximizes the probability to correctly stop in case of small or opposite effects while limiting the power loss and the probability of stopping the study ‘wrongly’. Our results clearly demonstrate the benefit of using such ‘optimal’ futility boundaries, especially compared to futility boundaries commonly applied in practice. Conclusions As the properties of futility boundaries are often not considered in practice and unfavorably chosen futility boundaries may imply bad properties of the study design, we recommend assessing the

  14. Establishing maintenance intervals based on measurement reliability of engineering endpoints.

    Science.gov (United States)

    James, P J

    2000-01-01

    Methods developed by the metrological community and principles used by the research community were integrated to provide a basis for a periodic maintenance interval analysis system. Engineering endpoints are used as measurement attributes on which to base two primary quality indicators: accuracy and reliability. Also key to establishing appropriate maintenance intervals is the ability to recognize two primary failure modes: random failure and time-related failure. The primary objective of the maintenance program is to avert predictable and preventable device failure, and understanding time-related failures enables service personnel to set intervals accordingly.

  15. Early Change in Proteinuria as a Surrogate Endpoint for Kidney Disease Progression: An Individual Patient Meta-analysis

    Science.gov (United States)

    Inker, Lesley A.; Levey, Andrew S.; Pandya, Kruti; Stoycheff, Nicholas; Okparavero, Aghogho; Greene, Tom

    2014-01-01

    Background It is controversial whether proteinuria is a valid surrogate endpoint for randomized trials in chronic kidney disease. Study Design Meta-analysis of individual patient level data. Setting & Population Individual patient data on 9008 patients from 32 randomized trials evaluating five intervention types. Selection Criteria for Studies Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least one further year of follow-up for the clinical outcome. Predictor Early change in proteinuria. Outcomes Doubling of serum creatinine, end stage renal disease or death. Results Early decline in proteinuria was associated with a lower risk of the clinical outcome (pooled HR, 0.74 per 50% reduction in proteinuria); this association was stronger at higher levels of baseline proteinuria. Pooled estimates for the proportion of treatment effect on the clinical outcome explained by early decline in proteinuria ranged from −7.0% (95% CI, −40.6% to 26.7%) to 43.9% (95% CI, 25.3% to 62.6%) across five intervention types. The direction of the pooled treatment effects on early change in proteinuria agreed with the direction of the treatment effect on the clinical outcome for all 5 intervention types, with the magnitudes of the pooled treatment effects on the two endpoints agreeing for 4 of the 5 intervention types. The pooled treatment effects on both endpoints were simultaneously stronger at higher levels of proteinuria. However, statistical power was insufficient to determine if differences in treatment effects on the clinical outcome corresponded to differences in treatment effects on proteinuria between individual studies. Limitations Limited variety of interventions tested and low statistical power for many chronic kidney disease clinical trials. Conclusions These results provide new evidence supporting the use of an early reduction in proteinuria as a

  16. The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress.

    Science.gov (United States)

    Antic, Nick A; Heeley, Emma; Anderson, Craig S; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R Doug

    2015-08-01

    The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. NCT00738179. ACTRN12608000409370. © 2015 Associated Professional Sleep Societies, LLC.

  17. Treatment of HIV-related primary central nervous system lymphoma with azt high dose, HAART, interleukin-2 and foscarnet in three patients

    Directory of Open Access Journals (Sweden)

    Marretta L

    2011-05-01

    Full Text Available Abstract Purpose Combined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL in an attempt to improve outcomes. Patients and methods Three patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT 1.6 gr. bid for two weeks, followed by oral AZT 250 mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART with a second nucleoside reverse transcriptase inhibitor (NRTI plus one protease inhibitor (PI and interleukin 2 (IL-2 subcutaneously 2 million units twice daily (bid plus foscarnet 90 mg/kg bid were administered on days 1-14. One patient received anti-EpsteinBarr virus (EBV-maintenance therapy with ganciclovir, followed by cidofovir 1. Results All patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT as second linetreatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histologically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable. Conclusion Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIVassociated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.

  18. Verification of models for ballistic movement time and endpoint variability.

    Science.gov (United States)

    Lin, Ray F; Drury, Colin G

    2013-01-01

    A hand control movement is composed of several ballistic movements. The time required in performing a ballistic movement and its endpoint variability are two important properties in developing movement models. The purpose of this study was to test potential models for predicting these two properties. Twelve participants conducted ballistic movements of specific amplitudes using a drawing tablet. The measured data of movement time and endpoint variability were then used to verify the models. This study was successful with Hoffmann and Gan's movement time model (Hoffmann, 1981; Gan and Hoffmann 1988) predicting more than 90.7% data variance for 84 individual measurements. A new theoretically developed ballistic movement variability model, proved to be better than Howarth, Beggs, and Bowden's (1971) model, predicting on average 84.8% of stopping-variable error and 88.3% of aiming-variable errors. These two validated models will help build solid theoretical movement models and evaluate input devices. This article provides better models for predicting end accuracy and movement time of ballistic movements that are desirable in rapid aiming tasks, such as keying in numbers on a smart phone. The models allow better design of aiming tasks, for example button sizes on mobile phones for different user populations.

  19. Cortical plasticity as a new endpoint measurement for chronic pain

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2011-07-01

    Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

  20. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  1. A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Carmen H Logie

    Full Text Available African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV-positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health. We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39 of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self-rated health. The model fit the data well: χ2 (45, n = 154 = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance

  2. A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen H; Jenkinson, Jesse I R; Earnshaw, Valerie; Tharao, Wangari; Loutfy, Mona R

    African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV-positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health). We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39) of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self-rated health. The model fit the data well: χ2 (45, n = 154) = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance health.

  3. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

    Science.gov (United States)

    Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-01-01

    Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to

  4. An examination of actor-partner social support effects on HIV-related problems and interpersonal outcomes among a sample of HIV-positive African American dyads.

    Science.gov (United States)

    Mosack, Katie E; Rafferty, Katherine A; Billig, Ashley K; Wendorf, Angela R; Brouwer, Amanda M; Stevens, Patricia

    2016-04-01

    Social support is an important resource that has been associated with better mental and physical health outcomes among HIV-positive people. However, researchers have not adequately explored how social support functions among HIV-positive African Americans. The purpose of the current study was to understand whether HIV-related support resources are associated with relational functioning and HIV-related problems among a sample of HIV-infected African American dyads. Exactly 34 HIV-infected (i.e., seroconcordant) dyads compromised of HIV-positive African American adults and their HIV-positive adult "informal supporters" from 3 Midwestern urban cities completed psychosocial questionnaires and a communication task. Using the actor-partner interdependence model, we analyzed dyadic data to determine whether there were actor and/or partner effects within dyadic relationships on measures of conflict and HIV-related problems, communication about these problems, and health symptoms. We found significant negative relationships between perceived support and HIV-related problems and perceptions of problem inequity within dyads and a positive relationship between perceived support and communication about these problems within dyads. Contrary to our expectations, we found no relationship between social support and HIV symptoms, relational conflict, or perceptions about dyadic partners' HIV-related problems. Although our study precludes drawing causal conclusions, we found evidence of a relationship between the personal experience of HIV-related problems, communication about these problems, and perceptions of social support among a small sample of HIV-infected African American dyads. These findings suggest the need to consider how support-related communication within HIV-infected dyads might influence and be influenced by problem perceptions. (c) 2016 APA, all rights reserved).

  5. A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada

    Science.gov (United States)

    Logie, Carmen H.; Jenkinson, Jesse I. R.; Earnshaw, Valerie; Tharao, Wangari; Loutfy, Mona R.

    2016-01-01

    African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV-positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health). We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39) of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self-rated health. The model fit the data well: χ2 (45, n = 154) = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance health. PMID

  6. Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

    Science.gov (United States)

    Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

    2008-10-01

    Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

  7. Attitudes and beliefs related to HIV/AIDS in urban religious congregations: barriers and opportunities for HIV-related interventions.

    Science.gov (United States)

    Bluthenthal, Ricky N; Palar, Kartika; Mendel, Peter; Kanouse, David E; Corbin, Dennis E; Derose, Kathryn Pitkin

    2012-05-01

    HIV-related stigmas have been seen as a barrier to greater religious congregation involvement in HIV prevention and care in the United States and elsewhere. We explored congregational and community norms and attitudes regarding HIV, sexuality, and drug use through a qualitative case study of 14 diverse religious congregations in Los Angeles County, California between December 2006 and May 2008. Data collected included semi-structured interviews with 57 clergy and lay leaders across the congregations, structured observations of congregational activities, review of archival documents, and a questionnaire on congregational characteristics. Across and within congregations, we found a wide range of views towards HIV, people with HIV, and populations at risk for HIV, from highly judgmental and exclusionary, to "loving the sinner, not the sin," to accepting and affirming. Attitudes and norms about HIV, homosexuality, and substance abuse appeared to be related to the type and intensity of congregational HIV-related activities. However, even among the higher activity congregations, we found a range of perceptions, including ones that were stigmatizing. Results suggest that affirming norms and attitudes are not a prerequisite for a congregation to initiate HIV activities, a finding relevant for HIV service providers and researchers seeking to engage congregations on this issue. HIV stigma reduction is not a prerequisite for congregational HIV involvement: both may occur simultaneously, or one before the other, and they dynamically affect each other. Strategies that are congruent with congregations' current levels of comfort and openness around HIV can themselves facilitate a process of attitudinal and normative change. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Comparing HIV-related symbolic stigma in six African countries: social representations in young people’s narratives

    Science.gov (United States)

    Winskell, Kate; Hill, Elizabeth; Obyerodhyambo, Oby

    2011-01-01

    HIV-related symbolic stigma arises from moralistic value judgements attached to people living with HIV and has negative consequences from both public health and human rights perspectives. Relatively little is known about cross-national variation in symbolic stigma. With the purpose of informing stigma reduction efforts within and across settings, we compared social representations of HIV in six African countries with estimated adult HIV prevalence rates ranging from 1 to 33%. Our study used a unique data source, namely a stratified random sample (n=586, ~5%) from 11,354 creative ideas contributed from six countries to a continent-wide HIV-related scriptwriting contest held between February and April2005. The narratives were written by equal numbers of males and females aged 10–24 in urban and rural areas of Swaziland, Namibia, Kenya, South-East Nigeria, Burkina Faso and Senegal. We combined three analytical approaches: descriptive statistics on certain quantifiable characteristics of the narratives, thematic data analysis, and a narrative-based approach. The association of HIV with outsiders (“othering”)and preoccupation with the circumstances of infection are more common in lower prevalence countries but vary substantially in tone depending on the sociocultural context. The highest proportion both of moralising narratives and of narratives with pessimistic outcomes come from South-East Nigeria and, to a lesser extent, from Kenya, countries with prevalence levels of 3.9 and 6.1% respectively, in which evangelical Christian movements, including Pentecostalism, have sizeable followings. The data provide a rare cross-cultural overview of symbolic stigma, identify country-specific needs, and point to strategies for future programming. Social representations from the highest prevalence countries, Swaziland and Namibia, and from lower prevalence Burkina Faso offer potential models for the framing of HIV in ways that serve to increase social proximity and counteract

  9. INDIVIDUALS VERSUS ORGANISMS VERSUS POPULATIONS IN THE DEFINITION OF ECOLOGICAL ASSESSMENT ENDPOINTS

    Science.gov (United States)

    The choice of endpoints for ecological risk assessments can be controversial, and some ecologists dismiss endpoints below the population level as irrelevant. This paper attempts to clarify the concept of assessment endpoints and what is meant by organismal or population attri...

  10. Screening for HIV-related PTSD: Sensitivity and specificity of the 17 ...

    African Journals Online (AJOL)

    Objectives: The identification of HIV-positive patients who exhibit criteria for Post traumatic Stress Disorder (PTSD) and related trauma symptomatology is of clinical importance in the maintenance of their overall wellbeing. This study assessed the sensitivity and specificity of the 17-item Post traumatic Stress Diagnostic Scale ...

  11. A survey of HIV-related knowledge among adult psychiatric patients ...

    African Journals Online (AJOL)

    Hughes E, Gray R. HIV prevention for people with serious mental illness: A survey of mental health workers' attitudes, knowledge and practice. Journal of Clinical Nursing 2008;. 18:591-600. 8. Naber D, Pajonk FG, Perro C, Lohmer B. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

  12. HIV-related oral candidiasis in Nigerian children: A marker of HIV ...

    African Journals Online (AJOL)

    This technique uses paramagnetic polymer beads coated with anti-CD4 monoclonal antibodies to capture and isolate the CD4 from the blood. Other investigations done were directed by the clinical condition of the patients. Information obtained was entered onto a data sheet and analysed for correlation of CD4 count with ...

  13. Regulatory considerations on endpoints in ovarian cancer drug development.

    Science.gov (United States)

    Balasubramaniam, Sanjeeve; Kim, Geoffrey S; McKee, Amy E; Pazdur, Richard

    2017-07-15

    Ovarian cancer remains a disease entity that is responsible for considerable morbidity and mortality among women worldwide. Modern drug research pipelines and accelerated drug development timelines applied to other disease entities have begun to make an impact on treatment options for patients with advanced ovarian cancer, as exemplified by the recent accelerated approval of 2 agents for this disease as the forerunners of a growing number of registrational trials. Regulatory flexibility for this serious and life-threatening condition spurs the consideration of intermediate endpoints for regulatory trial design, including potential applications in the development of newer therapeutic classes such as targeted therapies and immunotherapies for patients with advanced ovarian cancer. Cancer 2017;123:2604-8. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  14. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  15. Multiple critical endpoints in magnetized three flavor quark matter

    Science.gov (United States)

    Ferreira, Márcio; Costa, Pedro; Providência, Constança

    2018-01-01

    The magnetized phase diagram for three-flavor quark matter is studied within the Polyakov extended Nambu-Jona-Lasinio model. The order parameters are analyzed with special emphasis on the strange quark condensate. We show that the presence of an external magnetic field induces several critical endpoints (CEPs) in the strange sector, which arise due to the multiple phase transitions that the strange quark undergoes. The spinodal and binodal regions of the phase transitions are shown to increase with external magnetic field strength. The influence of strong magnetic fields on the isentropic trajectories around the several CEPs is analyzed. A focusing effect is observed on the region towards the CEPs that are related with the strange quark phase transitions. Compared to the chiral transitions, the deconfinement transition turns out to be less sensitive to the external magnetic field and the crossover nature is preserved over the whole phase diagram.

  16. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2).

    Science.gov (United States)

    Kappetein, Arie Pieter; Head, Stuart J; Généreux, Philippe; Piazza, Nicolo; van Mieghem, Nicolas M; Blackstone, Eugene H; Brott, Thomas G; Cohen, David J; Cutlip, Donald E; van Es, Gerrit-Anne; Hahn, Rebecca T; Kirtane, Ajay J; Krucoff, Mitchell W; Kodali, Susheel; Mack, Michael J; Mehran, Roxana; Rodés-Cabau, Josep; Vranckx, Pascal; Webb, John G; Windecker, Stephan; Serruys, Patrick W; Leon, Martin B

    2012-11-01

    The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for

  17. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.

    Science.gov (United States)

    Kappetein, A Pieter; Head, Stuart J; Généreux, Philippe; Piazza, Nicolo; van Mieghem, Nicolas M; Blackstone, Eugene H; Brott, Thomas G; Cohen, David J; Cutlip, Donald E; van Es, Gerrit-Anne; Hahn, Rebecca T; Kirtane, Ajay J; Krucoff, Mitchell W; Kodali, Susheel; Mack, Michael J; Mehran, Roxana; Rodés-Cabau, Josep; Vranckx, Pascal; Webb, John G; Windecker, Stephan; Serruys, Patrick W; Leon, Martin B

    2013-01-01

    The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for

  18. Urban farming: a non-traditional intervention for HIV-related distress.

    Science.gov (United States)

    Shacham, Enbal; Donovan, Michael F; Connolly, Shannon; Mayrose, Andrea; Scheuermann, Mary; Overton, E Turner

    2012-07-01

    As individuals with HIV are living longer with less morbidity, developing interventions that address co-morbidities are essential. Psychological distress symptoms fluctuate throughout HIV infection and interrupt self-care practices. This pilot study was conducted to test the implementation of a clinic-recruited sample to participate in a community-based urban farming intervention, and assess the efficacy of reducing psychological distress symptoms. While the changes were not statistically significant, participants reported less distress symptoms, improved overall general health, and reduced frequency of illicit drug use. These findings support the development of a larger scale study to examine the impact of this nontraditional intervention.

  19. Urban Farming: A Non-Traditional Intervention for HIV-Related Distress

    Science.gov (United States)

    Shacham, Enbal; Donovan, Michael F.; Connolly, Shannon; Mayrose, Andrea; Scheuermann, Mary; Overton, E. Turner

    2013-01-01

    As individuals with HIV are living longer with less morbidity, developing interventions that address co-morbidities are essential. Psychological distress symptoms fluctuate throughout HIV infection and interrupt self-care practices. This pilot study was conducted to test the implementation of a clinic-recruited sample to participate in a community-based urban farming intervention, and assess the efficacy of reducing psychological distress symptoms. While the changes were not statistically significant, participants reported less distress symptoms, improved overall general health, and reduced frequency of illicit drug use. These findings support the development of a larger scale study to examine the impact of this nontraditional intervention. PMID:21986870

  20. Sensation Seeking and Risk-Taking Propensity as Mediators in the Relationship between Childhood Abuse and HIV-Related Risk Behavior

    Science.gov (United States)

    Bornovalova, Marina A.; Gwadz, Marya A.; Kahler, Christopher; Aklin, W. M.; Lejuez, C. W.

    2008-01-01

    Objectives: Although a wealth of literature suggests that childhood physical, emotional, and sexual abuse are related to later-life HIV-related risk behaviors, few studies have explored disinhibition (e.g., impulsivity, risk-taking propensity, and sensation-seeking) as a risk factor in this relationship. Method: This cross-sectional study examined…

  1. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the

  2. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    DEFF Research Database (Denmark)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the set...

  3. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; de Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; de Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.; Gras, A. Luuk; van Wout, Angelique B.; Arnedo-Valero, Mireia; Sierra, Mariana de Paz; Rodriguez, Ana Torrecilla; Garcia, Juan Gonzalez; Arribas, Jose R.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Francioli, P.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Prins, Yerly S. J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Boer, K.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Vrouenraets, S. M. E.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Pronk, M. J. H.; Bravenboer, B.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; van der Feltz, M.; Nouwen, J. L.; Gelinck, L. B. S.; Verbon, A.; Rijnders, B. J. A.; van de Ven-de Ruiter, E. D.; Slobbe, L.; Haag, Den; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; van den Broek, P. J.; van Dissel, J. T.; Arend, S. M.; van Nieuwkoop, C.; de Boer, M. J. G.; Jolink, H.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; van Houte, D. P. F.; Polée, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; Juttmann, J. R.; van Kasteren, M. E. E.; Brouwer, A. E.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Stek, C. J.; Hoepelman, I. M.; Mudrikova, T.; Schneider, M. M. E.; Jaspers, C. A. J. J.; Ellerbroek, P. M.; Peters, E. J. G.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; van der Hilst, J. C. H.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; Margolick, Joseph B.; Plankey, Michael; Crain, Barbara; Dobs, Adrian; Farzadegan, Homayoon; Gallant, Joel; Johnson-Hill, Lisette; Sacktor, Ned; Selnes, Ola; Shepard, James; Thio, Chloe; Phair, John P.; Wolinsky, Steven M.; Badri, Sheila; Conover, Craig; O'Gorman, Maurice; Ostrow, David; Palella, Frank; Ragin, Ann; Detels, Roger; Martínez-Maza, Otoniel; Aronow, Aaron; Bolan, Robert; Breen, Elizabeth; Butch, Anthony; Fahey, John; Jamieson, Beth; Miller, Eric N.; Oishi, John; Vinters, Harry; Visscher, Barbara R.; Wiley, Dorothy; Witt, Mallory; Yang, Otto; Young, Stephen; Zhang, Zuo Feng; Rinaldo, Charles R.; Becker, James T.; Cranston, Ross D.; Martinson, Jeremy J.; Mellors, John W.; Silvestre, Anthony J.; Stall, Ronald D.; Muñoz, Alvaro; Abraham, Alison; Althoff, Keri; Cox, Christopher; D'Souza, Gypsyamber; Gange, Stephen J.; Golub, Elizabeth; Schollenberger, Janet; Seaberg, Eric C.; Su, Sol; Huebner, Robin E.; Dominguez, Geraldina; Moroni, M.; Angarano, G.; Antinori, A.; Carosi, G.; Cauda, R.; Monforte, A. d'Arminio; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Sagnelli, E.; Viale, P. L.; Von Schlosser, F.; d'Arminio Monforte, A.; Ammassari, A.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; de Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; Fanti, I.; Formenti, T.; Galli, Laura; Lorenzini, Patrizia; Montroni, M.; Giacometti, A.; Costantini, A.; Riva, A.; Tirelli, U.; Martellotta, F.; Ladisa, N.; Lazzari, G.; Verucchi, G.; Castelli, F.; Scalzini, A.; Minardi, C.; Bertelli, D.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Carnevale, G.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Leoncini, F.; Mazzotta, F.; Pozzi, M.; Cassola, G.; Viscoli, G.; Viscoli, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, P.; Rizzardini, G.; Ridolfo, A. L.; Foschi, A.; Salpietro, S.; Galli, A.; Bigoloni, A.; Spagnuolo, V.; Merli, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Bisio, L.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; de Marco, M.; Ferrari, C.; Borghi, R.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Narciso, P.; Tozzi, V.; Vullo, V.; d'Avino, A.; Zaccarelli, M.; Gallo, L.; Acinapura, R.; Capozzi, M.; Libertone, R.; Trotta, M. P.; Tebano, G.; Cattelan, A. M.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Raise, N. N.; Ebo, F.; Pellizzer, G.; Manfrin, V.; Law, M.; Petoumenos, K.; McManus, H.; Wright, S.; Bendall, C.; Moore, R.; Edwards, S.

    2013-01-01

    Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV

  4. Social networks and social support among ball-attending African American men who have sex with men and transgender women are associated with HIV-related outcomes.

    Science.gov (United States)

    Arnold, Emily A; Sterrett-Hong, Emma; Jonas, Adam; Pollack, Lance M

    2018-02-01

    The House Ball Community (HBC) is an understudied network of African American men who have sex with men and transgender women, who join family-like houses that compete in elaborate balls in cities across the United States. From 2011 to 2012, we surveyed 274 recent attendees of balls in the San Francisco Bay Area, focusing on social networks, social support, and HIV-related behaviours. Participants with a high percentage of alters who were supportive of HIV testing were significantly more likely to have tested in the past six months (p = .02), and less likely to have engaged in unprotected anal intercourse (UAI) in the past three months (p = .003). Multivariate regression analyses of social network characteristics, and social support, revealed that testing in the past six months was significantly associated with social support for safer sex, instrumental social support, and age. Similarly, UAI in the past three months was significantly associated with social support for safer sex, homophily based on sexual identity and HIV status. HIV-related social support provided through the HBC networks was correlated with recent HIV testing and reduced UAI. Approaches utilising networks within alternative kinship systems, may increase HIV-related social support and improve HIV-related outcomes.

  5. Trends in HIV-related behaviors and knowledge in Uganda, 1989-2005: evidence of a shift toward more risk-taking behaviors.

    Science.gov (United States)

    Opio, Alex; Mishra, Vinod; Hong, Rathavuth; Musinguzi, Joshua; Kirungi, Wilford; Cross, Anne; Mermin, Jonathan; Bunnell, Rebecca

    2008-11-01

    To describe recent trends in HIV-related behaviors and knowledge in Uganda between 1989 and 2005. Population-based, cross-sectional national surveys of adult women and men. Trend analysis of selected HIV-related behavior and knowledge indicators, using data from the 2004-2005 Uganda HIV/AIDS Sero-Behavioral Survey and the 2000-2001, 1995, and 1988-1989 Uganda Demographic and Health Surveys. Responses to similar questions across the different surveys were compared to determine trends in indicators. HIV/AIDS knowledge increased to a high level by 2001 and remained stable thereafter. Some self-reported risk behaviors improved, whereas others deteriorated. Among 15- to 24-year-old women and men, primary abstinence increased, from 23% in 1989 to 32% in 2005 and from 32% in 1995 to 42% in 2005, respectively. In men, there were increases in sex with multiple partners and sex with nonspousal partners, although reported condom use during nonspousal sex declined. Of men aged 15-49 years, self-reported multiple sex partnership increased from 24% in 2001 to 29% in 2005 and nonspousal sex increased from 28% in 2001 to 37% in 2005. Between 2001 and 2005, condom use during last nonspousal sex declined from 65% to 55% in men aged 15-24 years. Although substantial improvements in HIV-related risk behaviors and knowledge occurred since 1989, recent increases in some HIV-related risk behaviors were observed, indicating a shift toward more risk-taking behaviors. Prevention efforts should be reinvigorated to address this, otherwise the past success in the HIV fight will be reversed. Monitoring of HIV-related indicators should be continued.

  6. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive

    Directory of Open Access Journals (Sweden)

    Stephanie A Nixon

    2014-04-01

    Full Text Available Introduction: Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs, there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. Methods: This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Results: Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1 disability-related discrimination heightened when seeking HIV services, (2 communication barriers and related concerns with confidentiality, and (3 movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants’ profound concerns about poverty and unmet basic needs. Discussion: This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Conclusions: Despite the growing body of

  7. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive.

    Science.gov (United States)

    Nixon, Stephanie A; Cameron, Cathy; Hanass-Hancock, Jill; Simwaba, Phillimon; Solomon, Patricia E; Bond, Virginia A; Menon, Anitha; Richardson, Emma; Stevens, Marianne; Zack, Elisse

    2014-01-01

    Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs), there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1) disability-related discrimination heightened when seeking HIV services, (2) communication barriers and related concerns with confidentiality, and (3) movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants' profound concerns about poverty and unmet basic needs. This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Despite the growing body of literature on increased risk of exposure to HIV among HIV-negative PWDs, this is

  8. Reducing HIV-Related Risk Behaviors Among Injection Drug Users in Residential Detoxification

    Science.gov (United States)

    Booth, Robert E.; Campbell, Barbara K.; Mikulich-Gilbertson, Susan K.; Tillotson, Carrie J.; Choi, Dongseok; Robinson, James; Calsyn, Donald A.; Mandler, Raul N.; Jenkins, Lindsay M.; Thompson, Laetitia L.; Dempsey, Catherine L.; Liepman, Michael R.; McCarty, Dennis

    2010-01-01

    This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes. PMID:20652630

  9. A counterexample to an endpoint bilinear Strichartz inequality

    Directory of Open Access Journals (Sweden)

    Terence Tao

    2006-12-01

    Full Text Available The endpoint Strichartz estimate $$ | e^{itDelta} f |_{L^2_t L^infty_x(mathbb{R} imes mathbb{R}^2} lesssim |f|_{L^2_x(mathbb{R}^2} $$ is known to be false by the work of Montgomery-Smith [2], despite being only "logarithmically far" from being true in some sense. In this short note we show that (in sharp contrast to the $L^p_{t,x}$ Strichartz estimates the situation is not improved by passing to a bilinear setting; more precisely, if $P, P'$ are non-trivial smooth Fourier cutoff multipliers then we show that the bilinear estimate $$ | (e^{itDelta} P f (e^{itDelta} P' g |_{L^1_t L^infty_x(mathbb{R} imes mathbb{R}^2} lesssim |f|_{L^2_x(mathbb{R}^2} |g|_{L^2_x(mathbb{R}^2} $$ fails even when $P$, $P'$ have widely separated supports.

  10. Anal sex and associated HIV-related sexual risk factors among female sex workers in Andhra Pradesh, India.

    Science.gov (United States)

    Patra, Rajesh Kumar; Mahapatra, Bidhubhusan; Kovvali, Dolly; Proddutoor, Laxminarayana; Saggurti, Niranjan

    2012-11-01

    This study aims to understand the correlates of anal sex practices among female sex workers (FSWs) and examine the association of anal sex with HIV-related sexual risk factors in Andhra Pradesh, India. A cross-sectional behavioural survey was conducted in 2011 among 795 FSWs aged 18 years or older. Probability-based cluster sampling was used to select respondents from sex work hotspots. One-quarter (23%) of FSWs had practiced anal sex in the last year. The odds of practicing anal sex were higher among FSWs aged 35 years or more than in those aged less than 25 years (adjusted odds ratio (AOR): 2.05, Psex work compared to those having additional sources of income (AOR: 1.54, Pexperienced violence compared to those who had not (AOR: 2.80, Psex were more likely to experience sexually transmissible infection (STI) related symptoms than those practicing only vaginal sex. There was no association between anal sex practice and condom use. Anal sex is associated with STI symptoms, a factor for HIV risk. HIV intervention programmes need to educate FSWs about the risks associated with anal sex.

  11. Increasing HIV-related knowledge, communication, and testing intentions among Latinos: Protege tu Familia: Hazte la Prueba.

    Science.gov (United States)

    Rios-Ellis, Britt; Espinoza, Lilia; Bird, Mara; Garcia, Melawhy; D'Anna, Laura Hoyt; Bellamy, Laura; Scolari, Rosana

    2010-08-01

    Latinos are less likely to be aware of their HIV seropositivity than African Americans and Whites. 'Protege tu Familia: Hazte la Prueba' is a culturally and linguistically-sensitive HIV/AIDS prevention and testing program targeting Latino families. Using community-based participatory research techniques, Spanish-speaking bicultural community health workers helped develop and then used an educational flip chart and materials to conduct outreach and HIV prevention education in diverse settings. The intervention was created to increase HIV/AIDS-related knowledge, to improve communication regarding sexual risk, and to augment intentions to use condoms and test for HIV. A secondary purpose was to decrease HIV-related stigma by improving knowledge about transmission and reducing homophobia. Participants demonstrated significant increases in HIV knowledge, intention to practice safer sex and communicate sexual risk to partner(s), and intention to test for HIV. Improvements were also found in self-reported comfort levels when interacting with and caring for the HIV positive, thus decreasing HIV/AIDS-related stigma.

  12. The impact of HIV-related stigma on older and younger adults living with HIV disease: does age matter?

    Science.gov (United States)

    Emlet, Charles A; Brennan, David J; Brennenstuhl, Sarah; Rueda, Sergio; Hart, Trevor A; Rourke, Sean B

    2015-01-01

    The purpose of this study was to examine the independent influence of age on levels of HIV-related stigma experienced by adults living with HIV/AIDS. To accomplish this, cross-sectional data from the Ontario HIV Treatment Network Cohort Study were used to determine whether older age is associated with overall stigma among HIV-positive adults living in Ontario, Canada (n = 960). The relationship was also tested for enacted, anticipated, and internalized stigma. Covariates included sociodemographic (e.g., gender, sexual orientation, race) and psychosocial variables (e.g., depression). Modifying effects of covariates were also investigated. Those 55 and older have significantly lower overall and internalized stigma than adults under age 40, even when accounting for gender, sexual orientation, income, time since diagnosis, depression, maladaptive coping, and social support. Age does not predict enacted or Anticipated Stigma when accounting for the demographic and psychosocial variables. A significant interaction between depression and age suggests that stigma declines with age among those who are depressed but increases to age 50 and then decreases in older age groups among those who are not depressed. Age matters when it comes to understanding stigma among adults living with HIV/AIDS; however, the relationship between age and stigma is complex, varying according to stigma type and depression level.

  13. Self-esteem and "at risk" women:determinants and relevance to sexual and HIV-related risk behaviors.

    Science.gov (United States)

    Sterk, Claire E; Klein, Hugh; Elifson, Kirk W

    2004-01-01

    In this study, we describe the relationship between self-esteem and HIV-related risk behaviors, and explore what factors predict self-esteem levels of "at risk" women. Interviews were conducted with 250 (predominantly African American) women living in the Atlanta, Georgia metropolitan area between August 1997 and August 2000. A community identification process was used to identify potential study participants, with further expansion of the sample via targeted and theoretical sampling and ethnographic mapping procedures. Self-esteem was related to the number of times having oral sex, the number of times having sex with paying partners, the frequency of sexual risk-taking (all during the 90 days prior to interview), the number of different HIV risk behaviors practiced during the previous year, and condom use attitudes and self-efficacy. Greater involvement HIV risk behaviors was associated with lower self-esteem. Multivariate analyses revealed five significant predictors of women's self-esteem levels: race, religiosity, childhood experiences with emotional neglect, the number of money-related problems experienced, and the number of drug-related problems experienced. The findings indicate that self-esteem is highly relevant to "at risk" women's HIV risk behavior practices, and this has important implications for HIV intervention programs.

  14. Access to harm reduction and HIV-related treatment services inside Indian prisons: experiences of formerly incarcerated injecting drug users.

    Science.gov (United States)

    Chakrapani, Venkatesan; Kamei, Ram; Kipgen, Hoineilam; Kh, Jayanta Kumar

    2013-01-01

    The authors aimed to examine the incarceration experiences of injecting drug users in accessing harm reduction, and HIV-related services inside prisons in India. The authors conducted three focus groups with a purposive sample of 23 formerly incarcerated male IDUs and four key informant interviews with a former police official, a drug dealer and service providers. Data were analyzed using a constant comparative method. Participants reported availability of alcohol and injectable or oral drugs such as heroin, dextropropoxyphene, and marijuana inside prisons. Inmates obtained drugs and clean syringes (one syringe bought for 2.5-4 USD) through prison staff, and collected used syringes and needles from the dustbins in prison sickrooms. Needles and syringes were reused and shared. Prisons did not have needle and syringe programmes, detoxification, overdose management or opioid substitution treatment. Drug-using prison inmates faced several challenges in accessing antiretroviral treatment and HIV testing. The authors' findings emphasize the need to protect the health of injection drug-using inmates by introducing harm reduction programmes and removing barriers to HIV testing and antiretroviral treatment. This study illustrates, for the first time, the contexts behind high risk injecting drug use behaviours among prison inmates in India. It also highlights the lack of availability of harm reduction services such as needle and syringe programmes, drug detoxification and opioid substitution treatment inside prisons. Further, it demonstrates the difficulties faced by HIV-positive prison inmates in getting timely and uninterrupted antiretroviral treatment.

  15. The Use of Female Sex Workers Among Men in Nepal: Prevalence, STIs/HIV-Related Risk Behaviors, and Gender Ideology.

    Science.gov (United States)

    Shrestha, Roman; Karki, Pramila; Copenhaver, Michael

    Heterosexual sex involving female sex workers (FSWs) is widely documented for its role in facilitating the spread of sexually transmitted infections (STIs)/HIV. Critical to such studies, and increasingly considered essential to HIV prevention efforts, is the gender constructs and power dynamics within relationships. However, little efforts have been made, which focus on male clients of FSWs, particularly on the relationship between gender ideologies and men's sexual contact with FSWs, within the Nepali context. The present study aims to fill this critical gap by assessing the prevalence of use of FSWs and its association with STIs/HIV-related risk behaviors and gender ideologies among Nepali men. We used data from the nationally representative Nepal Demographic Health Survey (NDHS) 2011. For the purpose of analyses, we included a sample of 4,121 men, aged 15-49 years. During data analyses, we used multivariate logistic regression models, adjusted for the following variables: age, region, residence, religion, educational level, wealth index, employment status, and cigarette smoking status. Of the total sample, approximately 5% reported the use of FSWs in their lifetime. In regression models, men who had sex with FSWs were more likely to report a history of STIs [adjusted odds ratio (aOR): 3.03; 95% confidence interval (CI): 1.69-5.43; P gender roles and beliefs.

  16. Access and Quality of HIV-Related Point-of-Care Diagnostic Testing in Global Health Programs.

    Science.gov (United States)

    Fonjungo, Peter N; Boeras, Debrah I; Zeh, Clement; Alexander, Heather; Parekh, Bharat S; Nkengasong, John N

    2016-02-01

    Access to point-of-care testing (POCT) improves patient care, especially in resource-limited settings where laboratory infrastructure is poor and the bulk of the population lives in rural settings. However, because of challenges in rolling out the technology and weak quality assurance measures, the promise of human immunodeficiency virus (HIV)-related POCT in resource-limited settings has not been fully exploited to improve patient care and impact public health. Because of these challenges, the Joint United Nations Programme on HIV/AIDS (UNAIDS), in partnership with other organizations, recently launched the Diagnostics Access Initiative. Expanding HIV programs, including the "test and treat" strategies and the newly established UNAIDS 90-90-90 targets, will require increased access to reliable and accurate POCT results. In this review, we examine various components that could improve access and uptake of quality-assured POC tests to ensure coverage and public health impact. These components include evaluation, policy, regulation, and innovative approaches to strengthen the quality of POCT. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    Science.gov (United States)

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

  18. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

    Science.gov (United States)

    Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-07-13

    To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living

  19. Of fads, fashion, surrogate endpoints and dual RAS blockade.

    Science.gov (United States)

    Messerli, Franz H; Staessen, Jan A; Zannad, Faiez

    2010-09-01

    Dual renin-angiotensin system (RAS) blockade, mostly by combining an angiotensin converting enzyme (ACE) inhibitor with an angiotensin receptor blocker (ARB), is increasingly used in patients with hypertension and diabetes and/or proteinuria and in those with resistant heart failure. However, in the zest of achieving greater nephroprotection and cardioprotection, even patients with uncomplicated essential hypertension are not uncommonly treated with dual RAS blockade. In 2003 the COOPERATE trial, seemed to confirm that dual RAS blockade was beneficial and that proteinuria reduction was synonymous with nephroprotection. This study had to be withdrawn recently attesting to the suspicion that the data looked to good to be true. Moreover, the large prospective ONTARGET data argue against a nephroprotective effect of dual RAS blockade and together with renal findings from ACCOMPLISH, cast doubt on albuminuria/proteinuria being a reliable surrogate endpoint for renal outcome. Although in heart failure, dual RAS blockade had some benefit without reducing mortality, there remains a distinct safety issue with regard to hyperkalemia and elevated creatinine. Neither in ischaemic heart disease nor in left ventricular hypertrophy had dual RAS blockade any benefits when compared with single RAS blockade. Of note, the combination of an ACE inhibitor with an ARB was recently shown to reduce the risk of dementia. All dual RAS blockade may be created equal and the combination of valsartan with aliskiren, a direct renin inhibitor will be evaluated in diabetic patients in the prospective, randomized ALTITUDE study. For the time being, given the adverse effects and lack of consistent survival benefits, the use of dual RAS blockade should be avoided unless ironclad data emerge to the contrary.

  20. Chronic venous insufficiency of the lower limbs: suitability of transcutaneous blood gas monitoring as an endpoint to evaluate the outcome of pharmacological treatment with calcium dobesilate.

    Science.gov (United States)

    Marinello, J; Videla, S

    2004-12-01

    This pilot clinical trial was designed to further investigate the effects of calcium dobesilate in the treatment of chronic venous insufficiency (CVI) by means of a novel endpoint, transcutaneous oxygen pressure (TcPO2), and to evaluate the suitability of this endpoint for future research. Patients with mild to moderate CVI without active ulcers were randomized to receive calcium dobesilate 1000 mg/day, 2000 mg/day or placebo for 12 weeks. The primary efficacy endpoint was TcPO2 in the distal third of the internal side of the leg. Secondary endpoints included assessment of venous reflux and clinical symptoms. Patients in the dobesilate 1000 mg/day and placebo groups showed a mild increase in TcPO2 (adjusted mean change 2.67 mmHg and 1.56 mmHg, respectively), while those treated with 2000 mg/day of the active drug showed a decrease (adjusted mean change -0.53 mmHg). Conversely, clinical symptoms and venous reflux improved in all groups, especially with dobesilate, but differences with placebo were not significant. Treatment was very well tolerated. Although the absence of significant differences prevented confirmation of sensitivity, a trend favoring calcium dobesilate in clinical and hemodynamic parameters was observed. This improvement was not reflected by TcPO2. 2004 Prous Science.

  1. 'Triply cursed': racism, homophobia and HIV-related stigma are barriers to regular HIV testing, treatment adherence and disclosure among young Black gay men.

    Science.gov (United States)

    Arnold, Emily A; Rebchook, Gregory M; Kegeles, Susan M

    2014-06-01

    In the USA, young Black gay men are disproportionately impacted upon by HIV. In this qualitative study consisting of in-depth interviews with 31 young Black gay men and nine service providers, where we used thematic analysis to guide our interpretations, we found that HIV-related stigma and homophobia, within the larger societal context of racism, were related to sexual risk behaviour, reluctance to obtain HIV testing or care, lower adherence to treatment medication, and non-disclosure of a positive HIV status to sexual partners. Participants experienced homophobia and HIV-related stigma from churches and families within the Black community and from friends within the Black gay community, which otherwise provide support in the face of racism. Vulnerability to HIV was related to strategies that young Black gay men enacted to avoid being stigmatised or as a way of coping with alienation and rejection.

  2. “Triply cursed”: Racism, homophobia, and HIV-related stigma are barriers to regular HIV testing, treatment adherence, and disclosure among young Black gay men

    Science.gov (United States)

    Arnold, Emily A.; Rebchook, Gregory M.; Kegeles, Susan M.

    2014-01-01

    In the USA, young Black gay men are disproportionately impacted by HIV. In this qualitative study consisting of in-depth interviews with 31 young Black gay men and 9 service providers, where we used thematic analysis to guide our interpretations, we found that HIV-related stigma and homophobia, within the larger societal context of racism, were related to sexual risk behaviour, reluctance to obtain HIV testing or care, lower adherence to treatment medication, and disclosure of a positive HIV status to sexual partners. Participants experienced homophobia and HIV-related stigma from churches and families within the Black community, and from friends within the Black gay community, that otherwise provide support in the face of racism. Vulnerability to HIV was related to strategies that young Black gay men enacted to avoid being stigmatised or as a way of coping with their alienation and rejection. PMID:24784224

  3. The role of risk perception and efficacy cognitions in the prediction of HIV-related preventive behavior and condom use.

    Science.gov (United States)

    Bengel, J; Belz-merk, M; Farin, E

    1996-01-01

    The salience of the Protection Motivation Theory to HIV preventive behavior was investigated in a sample of 468 heterosexual men 20-45 years of age recruited in Germany and at vacation spots in Spain. This theory conceptualizes self-protective behaviors as a function of the severity of the threat, perceived personal vulnerability to this threat, the availability of coping responses, and the effectiveness of these responses. Cognitive variables measured included perceived severity of the threat of AIDS, sexual self-efficacy expectancy, self-efficacy expectations in terms of sexual communication skills, response efficacy, and attitude toward condom use. On a scale of 1 (low) to 6 (high), perceived severity of the AIDS threat averaged 5.3, individual susceptibility ratings averaged 3.5, and susceptibility of peers had a mean of 4.9. Although 33% of respondents had made behavioral changes in response to the AIDS epidemic, only 15% always used condoms while 12% used them occasionally. Self-efficacy expectancy with regard to assertiveness and use of preventive measures emerged as the most significant predictor of HIV-related behaviors. The causal analyses indicated that high communicative self-efficacy expectancy is associated with high-risk sexual behaviors, while self-efficacy expectancy regarding assertiveness and the use of preventive measures promotes risk reduction. These associations were strongest in men over 26 years of age, singles, and tourists. These findings suggest a need for interventions for couples such as assertiveness training and guidance on communicating about sex and AIDS. Also demonstrated was the need for AIDS education programs to identify where participants are in terms of perceiving the threat of and coping with the AIDS epidemic and promote conditions that will help people advance to the next stage.

  4. “Triply cursed”: Racism, homophobia, and HIV-related stigma are barriers to regular HIV testing, treatment adherence, and disclosure among young Black gay men

    OpenAIRE

    Arnold, Emily A.; Rebchook, Gregory M.; Kegeles, Susan M.

    2014-01-01

    In the USA, young Black gay men are disproportionately impacted upon by HIV. In this qualitative study consisting of in-depth interviews with 31 young Black gay men and nine service providers, where we used thematic analysis to guide our interpretations, we found that HIV-related stigma and homophobia, within the larger societal context of racism, were related to sexual risk behaviour, reluctance to obtain HIV testing or care, lower adherence to treatment medication, and non-disclosure of a p...

  5. Details for Manuscript Number SSM-D-07-01631R1 “HIV-Related Stigma: Adapting a Theoretical Framework for Use in India”

    OpenAIRE

    Steward, Wayne T.; Herek, Gregory M; Ramakrishna, Jayashree; Bharat, Shalini; Chandy, Sara; Wrubel, Judith; Ekstrand, Maria L

    2008-01-01

    Stigma complicates the treatment of HIV worldwide. We examined whether a multi-component framework, initially consisting of enacted, felt normative, and internalized forms of individual stigma experiences, could be used to understand HIV-related stigma in Southern India. In Study 1, qualitative interviews with a convenience sample of 16 people living with HIV revealed instances of all three types of stigma. Experiences of discrimination (enacted stigma) were reported relatively infrequently. ...

  6. HIV-related stigma and self-disclosure: the mediating and moderating role of anticipated discrimination among people living with HIV/AIDS in Akure Nigeria.

    Science.gov (United States)

    Olley, B O; Ogunde, M J; Oso, P O; Ishola, A

    2016-01-01

    Although links between HIV-related stigma and self-disclosure of HIV status among people living with HIV have been well established, it is unclear whether levels of perceived discrimination are differentially associated with self-disclosure. The present study using a multi-factorial survey design investigated the role of stigma and other self-related factors (e.g., anticipated discrimination, self-esteem, HIV-related factors [e.g., drug use combination; knowledge of duration of HIV diagnosis] and socio-demographic factors [e.g., multiple spouse; age, gender, educational level] and psychological distress [depression]) in self-disclosure among People living with HIV/AIDs has been added (PLWHA) on follow-up management in State Specialist Hospital Akure, Nigeria. One hundred and thirty nine HIV/AIDS patients (49 males and 90 females) participated in the study. Mean age and mean time in months since diagnosis were 39.56 ± 10.26 and 37.78 ± 48.34, respectively. Four variables: multiple spouse, anticipated discrimination, HIV-related stigma and self-esteem were related to self-disclosure at (p self-esteem (Sobel test: z = 2.09, Aroian = 2.06, p stigma (Sobel test: z = 2.78, Aroaian = 2.75 p stigma t (5, 137) = 1.69, p > .05, self-esteem t (5, 137) = .59, p > .05 and anticipated discrimination were non-significant, suggesting a non-moderation effect of discrimination and disclosure. The results indicate that anticipated discrimination may impact HIV-related stigma to reduce self-disclosure among the PLWHAs in Akure, Nigeria. Interventions should incorporate anticipated discrimination in educational programs of HIV stigma in encouraging self-disclosure among PLWHAs.

  7. Influence of religious affiliation and education on HIV knowledge and HIV-related sexual behaviors among unmarried youth in rural central Mozambique.

    Science.gov (United States)

    Noden, Bruce H; Gomes, Aurelio; Ferreira, Aldina

    2010-10-01

    The interactions between religious affiliation, education, HIV knowledge, and HIV-related sexual behaviors among African church youth are poorly understood. In this socio-demographic study, 522 unmarried youth 12-28 years old in rural central Mozambique were surveyed with a structured questionnaire. Using binary logistic regression analysis, we used religious affiliation and education to measure influence on (1) HIV transmission and prevention knowledge and attitudes and (2) HIV-related sexual behaviors among youth. Religiously affiliated males were more likely than non-religious males to know when a condom should be used, respond correctly to HIV transmission questions and respond with less stigma to HIV-related scenarios. Increased levels of education among males corresponded significantly to increased knowledge of condom usage and HIV prevention strategies and less likelihood to respond with stigma. Only education levels influenced young female responses. Religious affiliation and education had minimal effects on sexual activity, condom usage, and multiple partnerships. African Independent Church/Zionist males were 1.6 times more likely to be sexually inexperienced than non-religious males but were also significantly less likely to use condoms (0.23, p=0.024). Non-religious youth were most likely to have visited sex workers and did not use condoms. These results suggest that religious affiliation, possibly as the result of educational opportunities afforded by religious-affiliated schools, is contributing to increased HIV transmission and prevention knowledge among youth in rural Central Mozambique but not influencing HIV-related sexual behavior. The need exists to strengthen the capacity of religious congregations to teach about HIV/AIDS and target non-religious youth with HIV transmission and prevention information.

  8. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa); Ackermann, Christelle [University of Stellenbosch, Department of Radiology, Stellenbosch (South Africa); Laughton, Barbara; Cotton, Mark [Stellenbosch University and Tygerberg Children' s Hospital, Children' s Infectious Diseases Research Unit, Stellenbosch (South Africa); Tomazos, Nicollette [University of Cape Town, Faculty of Commerce, Department of Management Studies, Cape Town (South Africa); Spottiswoode, Bruce [University of Cape Town, MRC/UCT Medical Imaging Research Unit, Department of Human Biology, Cape Town (South Africa); Mauff, Katya [University of Cape Town, Department of Statistical Sciences, Cape Town (South Africa); Pettifor, John M. [University of the Witwatersrand, MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, Witwatersrand (South Africa)

    2015-07-15

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  9. Right-handed currents at B→ K l+l− kinematic endpoint

    Indian Academy of Sciences (India)

    2017-10-09

    Oct 9, 2017 ... The recent LHCb measured values of these observables are used to conclude an evidence of right-handed currents at the kinematic endpoint of this decay mode. As the conclusion is drawn at the maximum dilepton invariant mass square ( q 2 ) kinematic endpoint, it relies only on heavy quark symmetries ...

  10. 78 FR 46351 - Trial Designs and Endpoints for Liver Disease Secondary to Nonalcoholic Steatohepatitis; Public...

    Science.gov (United States)

    2013-07-31

    ... HUMAN SERVICES Food and Drug Administration Trial Designs and Endpoints for Liver Disease Secondary to... Research in cosponsorship with the American Association for the Study of Liver Diseases (AASLD) is announcing a 2-day public workshop entitled ``Trial Designs and Endpoints for Liver Disease Secondary to...

  11. Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

  12. Restoration for the future: endpoints, targets, and indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo. Schweitzer

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

  13. Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

    Science.gov (United States)

    Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

    2017-05-01

    Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

  14. SU-C-210-01: Are Clinically Relevant Dosimetric Endpoints Significantly Better with Gating of Lung SBRT Vs. ITV-Based Treatment?: Results of a Large Cohort Investigation Analyzing Predictive Dosimetric Indicators as a Function of Tumor Volume and Motion Amplitude

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J; Zhao, B; Ajlouni, M; Movsas, B; Chetty, I.J. [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To quantitatively compare patient internal target volume (ITV)-based plans with retrospectively generated gated plans to evaluate potential dosimetric improvements in lung toxicity from gated radiotherapy. Methods: Evaluation was conducted for 150 stereotactic body radiation therapy (SBRT) treatment plans for 128 early-stage (T1–T3, <5cm) NSCLC patients. PTV margins were: ITV+5 mm (ITV-plan) and GTV+5 mm (Gated-plan). ITV-based and gated treatment plans were compared on the same free-breathing CT. ITV-based plan constraints were used to re-optimize and recalculate new gated plans. Plans were generated for 3 fractionation regimens: 3×18Gy, 4×12Gy (original), and 5×10Gy. Physical dose was converted to equivalent dose in 2Gy fractions (EQD2), which was used to determine mean lung dose (MLD) and percent volume of lung receiving ≥20Gy (V20). MLD and V20 differences between gating and ITV-based plans were analyzed as a function of both three-dimensional (3D) motion and tumor volume. The low dose region, V5, was also evaluated. Results: MLD and V20 differences between gated and ITV-based plans were larger for lower (1.48±1.32Gy and 1.44±1.29%) than for upper lobe tumors (0.89±0.74Gy and 0.92±0.71%) due to smaller tumor motion (2.9±3.4mm) compared to lower lobe tumors (8.1±6.1mm). Average differences of <1–2% were noted in V5 between ITV and gated plans. Dosimetric differences between gating and ITV-based methods increased with increasing tumor motion and decreasing tumor volume. Overall, average MLD (8.04±3.92Gy) and V20 (8.29±4.33%) values for ITV-based plans were already well below clinical guidelines, even for the 3×18Gy dose scheme, for which largest differences were noted relative to gated plans. Similar results were obtained for 5×10Gy and 4×12Gy regimens. Conclusion: Clinically relevant improvement in pulmonary toxicity, based on predictors of radiation pneumonitis (MLD and V20) was not generally observed, though improvement for tumors

  15. Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

    Directory of Open Access Journals (Sweden)

    Jun Hata

    Full Text Available Endpoint adjudication committees (EPAC are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov NCT00145925.The ADVANCE trial was a multicentre, 2 × 2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death and microvascular (new or worsening nephropathy and retinopathy events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85% with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals in the primary outcome for the blood pressure lowering comparison were 8% (-1 to 15% based on the investigator-reported events and 9% (0 to 17% based on the EPAC-based events (P for homogeneity = 0.70. The corresponding findings for the glucose comparison were 8% (1 to 15% and 10% (2% to 18% (P for homogeneity = 0.60. The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6.The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment.

  16. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans.

    Science.gov (United States)

    Yang, Zhendong; Xue, Kathy S; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-12-02

    Aflatoxins B₁ (AFB₁), deoxynivalenol (DON), fumonisin B₁ (FB₁), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB₁ toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB₁, FB₁, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  17. The role of HIV-related stigma in utilization of skilled childbirth services in rural Kenya: a prospective mixed-methods study.

    Directory of Open Access Journals (Sweden)

    Janet M Turan

    Full Text Available Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.From 2007-2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598; 411 (69% were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48 aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22-0.88.Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of

  18. Prevalence and predictors of HIV-related stigma among institutional- and community-based caregivers of orphans and vulnerable children living in five less-wealthy countries

    Directory of Open Access Journals (Sweden)

    Messer Lynne C

    2010-08-01

    Full Text Available Abstract Background In the face of the HIV/AIDS epidemic that has contributed to the dramatic increase in orphans and abandoned children (OAC worldwide, caregiver attitudes about HIV, and HIV-related stigma, are two attributes that may affect caregiving. Little research has considered the relationship between caregiver attributes and caregiver-reported HIV-related stigma. In light of the paucity of this literature, this paper will describe HIV-related stigma among caregivers of OAC in five less wealthy nations. Methods Baseline data were collected between May 2006 through February 2008. The sample included 1,480 community-based and 192 institution-based caregivers. Characteristics of the community-based and institution-based caregivers are described using means and standard deviations for continuous variables or counts and percentages for categorical variables. We fit logistic regression models, both for the full sample and separately for community-based and institution-based caregivers, to explore predictors of acceptance of HIV. Results Approximately 80% of both community-based and institution-based caregivers were female; and 84% of institution-based caregivers, compared to 66% of community-based caregivers, said that they would be willing to care for a relative with HIV. Similar proportions were reported when caregivers were asked if they were willing to let their child play with an HIV-infected child. In a multivariable model predicting willingness to care for an HIV-infected relative, adjusted for site fixed effects, being an institution-based caregiver was associated with greater willingness (less stigma than community-based caregivers. Decreased willingness was reported by older respondents, while willingness increased with greater formal education. In the adjusted models predicting willingness to allow one's child to play with an HIV-infected child, female gender and older age was associated with less willingness. However, willingness

  19. Experiences of HIV-related stigma among HIV-positive older persons in Uganda – a mixed methods analysis

    Science.gov (United States)

    Kuteesa, Monica O.; Wright, Stuart; Seeley, Janet; Mugisha, Joseph; Kinyanda, Eugene; Kakembo, Frederick; Mwesigwa, Richard; Scholten, Francis

    2014-01-01

    Abstract There is limited data on stigma among older HIV-infected adults in sub-Saharan Africa. We describe the experiences of stigma and disclosure in a cohort of HIV-positive older people in Uganda. Using data from the Wellbeing of Older Peoples' Study of Kalungu (rural site) and Wakiso district (peri-urban site) residents, we measured self-reported stigma levels for 183 respondents (94 on antiretroviral therapy (ART); 88, not on ART) using a stigma score generated using three questions on stigma perceptions where 0 meant no stigma at all and 100 was maximum stigma. Based on two questions on disclosure, an overall score was computed. High disclosure was assigned to those who often or very often disclosed to the family and were never or seldom afraid to disclose elsewhere. We examined the experiences of HIV stigma of 25 adults (52% females) using semi-structured, open-ended interviews and monthly oral diaries over one year. Mean age of the respondents was 70 years (range 60–80 years) and 80% of all respondents were enrolled in ART. Interview transcripts were analysed using thematic content analysis. Overall, 55% of respondents had a high disclosure score, meaning they disclosed easily, and 47% had a high stigma score. The stigma scores were similar among those with high and low disclosure scores. In multivariate analyses with disclosure and stigma scores as dependent variables none of the respondents' characteristics had a significant effect at the 5% level. Qualitative data revealed that stigma ranges from: (1) perceptions (relatively passive, but leading to behaviour such as gossip, especially if not intended maliciously); to (2) discriminatory behaviour (active or enacted stigma; from malicious gossip to outright discrimination). Despite the relatively high levels of disclosure, older people suffer from high levels of stigma of various forms apart from HIV-related stigma. Efforts to assess for different forms of stigma at an individual level deserve greater

  20. Differences in Substance Use, Psychosocial Characteristics and HIV-Related Sexual Risk Behavior Between Black Men Who Have Sex with Men Only (BMSMO) and Black Men Who Have Sex with Men and Women (BMSMW) in Six US Cities

    National Research Council Canada - National Science Library

    Dyer, Typhanye P; Regan, Rotrease; Wilton, Leo; Harawa, Nina T; Ou, San San; Wang, Lei; Shoptaw, Steve

    2013-01-01

    We assessed associations in substance use, psychosocial characteristics, and HIV-related sexual risk behaviors, comparing characteristics of Black men who only have sex with other men only (BMSMO; n = 839...

  1. Relevance weighting of tier 1 endocrine screening endpoints by rank order.

    Science.gov (United States)

    Borgert, Christopher J; Stuchal, Leah D; Mihaich, Ellen M; Becker, Richard A; Bentley, Karin S; Brausch, John M; Coady, Katie; Geter, David R; Gordon, Elliot; Guiney, Patrick D; Hess, Frederick; Holmes, Catherine M; LeBaron, Matthew J; Levine, Steve; Marty, Sue; Mukhi, Sandeep; Neal, Barbara H; Ortego, Lisa S; Saltmiras, David A; Snajdr, Suzanne; Staveley, Jane; Tobia, Abraham

    2014-02-01

    Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis-based WoE framework was recently published focusing on the U.S. EPA's Tier 1 Endocrine Screening Battery (ESB) as an example. The framework recommends weighting each experimental endpoint according to its relevance for deciding eight hypotheses addressed by the ESB. Here we present detailed rationale for weighting the ESB endpoints according to three rank ordered categories and an interpretive process for using the rankings to reach WoE determinations. Rank 1 was assigned to in vivo endpoints that characterize the fundamental physiological actions for androgen, estrogen, and thyroid activities. Rank 1 endpoints are specific and sensitive for the hypothesis, interpretable without ancillary data, and rarely confounded by artifacts or nonspecific activity. Rank 2 endpoints are specific and interpretable for the hypothesis but less informative than Rank 1, often due to oversensitivity, inclusion of narrowly context-dependent components of the hormonal system (e.g., in vitro endpoints), or confounding by nonspecific activity. Rank 3 endpoints are relevant for the hypothesis but only corroborative of Ranks 1 and 2 endpoints. Rank 3 includes many apical in vivo endpoints that can be affected by systemic toxicity and nonhormonal activity. Although these relevance weight rankings (WREL ) necessarily involve professional judgment, their a priori derivation enhances transparency and renders WoE determinations amenable to methodological scrutiny according to basic scientific premises, characteristics that cannot be assured by processes in which the rationale for decisions is provided post hoc. © 2014 Wiley Periodicals, Inc.

  2. A dynamic power prior for borrowing historical data in noninferiority trials with binary endpoint.

    Science.gov (United States)

    Liu, G Frank

    2018-02-01

    Traditionally, noninferiority hypotheses have been tested using a frequentist method with a fixed margin. Given that information for the control group is often available from previous studies, it is interesting to consider a Bayesian approach in which information is "borrowed" for the control group to improve efficiency. However, construction of an appropriate informative prior can be challenging. In this paper, we consider a hybrid Bayesian approach for testing noninferiority hypotheses in studies with a binary endpoint. To account for heterogeneity between the historical information and the current trial for the control group, a dynamic P value-based power prior parameter is proposed to adjust the amount of information borrowed from the historical data. This approach extends the simple test-then-pool method to allow a continuous discounting power parameter. An adjusted α level is also proposed to better control the type I error. Simulations are conducted to investigate the performance of the proposed method and to make comparisons with other methods including test-then-pool and hierarchical modeling. The methods are illustrated with data from vaccine clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Exploring HIV-related stigma among HIV-infected men who have sex with men in Beijing, China: a correlation study.

    Science.gov (United States)

    Li, Zhen; Hsieh, Evelyn; Morano, Jamie P; Sheng, Yu

    2016-11-01

    Human immunodeficiency virus (HIV)-related stigma among HIV-infected men who have sex with men (MSM) has been associated with adverse health outcomes, including poor adherence to antiretroviral therapy and care, and increased participation in behaviors linked to higher rates of HIV transmission. In China, the incidence of HIV is growing more rapidly among MSM than among other subgroups. This study characterizes and quantifies HIV stigma among HIV-infected MSM in Beijing, China, which arguably may be driving this epidemic. A cross-sectional survey study was performed among 266 HIV-positive MSM in Beijing, China, in 2014. The Berger HIV Stigma Scale was used to measure levels of HIV-related stigma. Participants additionally answered questions regarding socio-demographic characteristics and HIV-associated risk factors; previously validated Mandarin-language scales assessed depression, coping style, and social support networks. Multivariable linear regression models were used to identify variables significantly associated with HIV stigma. The mean overall HIV stigma score among the study population was 112.78 ± 18.11 (score range: 40-160). Higher HIV stigma scores were positively associated with depression (β = 7.99, 95% CI:3.69, 12.29, p coping skills (β = 0.64, 95% CI:0.21,1.08, p stigma. The results of this study can inform the development of culturally sensitive interventions to reduce HIV-related stigma among MSM with HIV in China, with the overarching goal of reducing HIV transmission in this vulnerable population.

  4. Exposure to pornographic videos and its effect on HIV-related sexual risk behaviours among male migrant workers in southern India.

    Directory of Open Access Journals (Sweden)

    Bidhubhusan Mahapatra

    Full Text Available OBJECTIVE: Research on pornography and its association with HIV-related sexual behaviours is limited in India. This study aims to examine the prevalence and correlates of viewing pornographic videos and examine its associations with HIV-related sexual risk behaviours among male migrant workers in India. METHODS: Data were drawn from a cross-sectional survey conducted in 2007-08 across 21 districts in four states of India. Respondents included 11,219 male migrants aged 18 years or older, who had migrated to at least two places in the past two years for work. Bivariate and multivariate methods were used to examine the association between viewing pornography and HIV-related sexual risk behaviours. RESULTS: Two-fifths (40% of the migrants had viewed pornographic videos in one month prior to the survey. Migrants aged 25-29 years, literate, unmarried and away from native village for more than five years were more likely to view pornography than their counterparts. Migrants who viewed pornographic videos were more likely to engage in paid (Adjusted odds ratio [AOR]: 4.2, 95% confidence interval [CI]: 3.7-4.8 and unpaid sex (AOR: 4.2, 95% CI: 3.7-4.7, report inconsistent condom use in paid sex (AOR: 2.3, 95% CI: 1.7-3.0 and experience STI-like symptoms (AOR: 1.7, 95% CI: 1.5-1.8 than their counterparts. CONCLUSIONS: The findings regarding migrants' exposure to pornography and its linkage with high HIV risk behaviour suggest that the HIV prevention programmes for migrants need to be more innovative to communicate on the negative-effects of viewing pornography. More importantly, programmes need to find alternative ways to engage migrants in infotainment activities during their leisure time in an effort to reduce their exposure to pornographic videos as well as risky sexual behaviours.

  5. Prevalence and pattern of HIV-related malnutrition among women in sub-Saharan Africa: a meta-analysis of demographic health surveys

    Directory of Open Access Journals (Sweden)

    Uthman Olalekan A

    2008-07-01

    Full Text Available Abstract Background The world's highest HIV infection rates are found in Sub-Saharan Africa (SSA, where adult prevalence in most countries exceeds 25%. Food shortages and malnutrition have combined with HIV/AIDS to bring some countries to the brink of crisis. The aim of this study was to describe prevalence of malnutrition among HIV-infected women and variations across socioeconomic status using data from 11 countries in SSA. Methods This study uses meta-analytic procedures to synthesize the results of most recent data sets available from Demographic and Health Surveys of 11 countries in SSA. Pooled prevalence estimates and 95% confidence intervals were calculated using random-and fixed-effects models. Subgroup and leave-one-country-out sensitivity analyses were also carried out. Results Pooling the prevalence estimates of HIV-related malnutrition yielded an overall prevalence of 10.3% (95% CI 7.4% to 14.1% with no statistically significant heterogeneity (I2 = 0.0%, p = .903. The prevalence estimates decreased with increasing wealth index and education attainment. The pooled prevalence of HIV-related malnutrition was higher among women residing in rural areas than among women residing in urban areas; and lower among women that were professionally employed than unemployed or women in agricultural or manual work. Conclusion Prevalence of HIV-related malnutrition among women varies by wealth status, education attainment, occupation, and type of residence (rural/urban. The observed socioeconomic disparities can help provide more information about population subgroups in particular need and high risk groups, which may in turn lead to the development and implementation of more effective intervention programs.

  6. Perceived HIV stigma among children in a high HIV-prevalence area in central China: beyond the parental HIV-related illness and death.

    Science.gov (United States)

    Lin, Xiuyun; Zhao, Guoxiang; Li, Xiaoming; Stanton, Bonita; Zhang, Liying; Hong, Yan; Zhao, Junfeng; Fang, Xiaoyi

    2010-05-01

    (1) Examine the psychometric properties of two parallel measures of HIV-related stigma (i.e., perceived public stigma and children's personal stigma against people living with HIV/AIDS [PLWHA]) among children affected by HIV/AIDS. (2) Examine whether expressions of stigma measures differ by child's sex, developmental stage, family socioeconomic status (SES), or orphanhood status (i.e., AIDS orphans, vulnerable children, and comparison children). (3) Examine the association between HIV-related stigma and children's psychosocial adjustments among these children. Cross-sectional data were collected from 755 AIDS orphans (children who had lost one or both their parents to AIDS), 466 vulnerable children who lived with HIV infected parents, and 404 comparison children who did not experience HIV-related illness and death in their families. The measures included perceived public stigma, personal stigma, depressive symptoms, loneliness, self-esteem, future expectations, hopefulness about the future, and perceived control over the future. Both stigma scales were positively associated with psychopathological symptoms (e.g., depression, loneliness) and negatively associated with psychosocial well-being (e.g., self-esteem, positive future expectation, hopefulness about future, and perceived control over the future). Both stigma measures contribute to children's psychosocial problems independent of their orphanhood status and other key demographic factors. Community-wide stigma reduction and psychological support should be part of the care efforts for children affected by AIDS. Stigma reduction efforts should not only target the stigma against PLWHA but also possible stigma against the entire community (e.g., villages) with a high prevalence of HIV/AIDS. The stigma reduction efforts also needs to be appropriate for children's age, gender, family SES, and AIDS experience in the family. Future research should explore individual and contextual factors such as social support, coping

  7. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    OpenAIRE

    Yumusak, Semih; Dogdu, Erdogan; KODAZ, Halife; Kamilaris, Andreas

    2016-01-01

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...

  8. Autonomous Sub-Pixel Satellite Track Endpoint Determination for Space Based Images

    Energy Technology Data Exchange (ETDEWEB)

    Simms, L M

    2011-03-07

    An algorithm for determining satellite track endpoints with sub-pixel resolution in spaced-based images is presented. The algorithm allows for significant curvature in the imaged track due to rotation of the spacecraft capturing the image. The motivation behind the subpixel endpoint determination is first presented, followed by a description of the methodology used. Results from running the algorithm on real ground-based and simulated spaced-based images are shown to highlight its effectiveness.

  9. End-point controller design for an experimental two-link flexible manipulator using convex optimization

    Science.gov (United States)

    Oakley, Celia M.; Barratt, Craig H.

    1990-01-01

    Recent results in linear controller design are used to design an end-point controller for an experimental two-link flexible manipulator. A nominal 14-state linear-quadratic-Gaussian (LQG) controller was augmented with a 528-tap finite-impulse-response (FIR) filter designed using convex optimization techniques. The resulting 278-state controller produced improved end-point trajectory tracking and disturbance rejection in simulation and experimentally in real time.

  10. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2016-10-01

    Chapel Hill, North Carolina, 27599 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research...and manuscript was published in European Urology (Basch, Euro Urol 2015) In addition, patient understanding and acceptance of the worst pain NRS...meriting prospective validation in phase 3 studies. (Basch, Euro Urol, 2015) 7. Results from this phase II pain assessment served as rationale for

  11. CLINICAL ENDPOINTS FOR THE STUDY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Sadda, SriniVas R; Chakravarthy, Usha; Birch, David G; Staurenghi, Giovanni; Henry, Erin C; Brittain, Christopher

    2016-10-01

    To summarize the recent literature describing the application of modern technologies in the study of patients with geographic atrophy (GA) secondary to age-related macular degeneration. Review of the literature describing the terms and definitions used to describe GA, imaging modalities used to capture and measure GA, and the tests of visual function and functional deficits that occur in patients with GA. In this paper, we describe the evolution of the definitions used to describe GA. We compare imaging modalities used in the characterization of GA, report on the sensitivity and specificity of the techniques where data exist, and describe the correlations between these various modes of capturing the presence of GA. We review the functional tests that have been used in patients with GA, and critically examine their ability to detect and quantify visual deficits. Ophthalmologists and retina specialists now have a wide range of assessments available for the functional and anatomic characterization of GA in patients with age-related macular degeneration. To date, studies have been limited by their unimodal approach, and we recommend that future studies of GA use multimodal imaging. We also suggest strategies for the optimal functional testing of patients with GA.

  12. Tree-Based Methods for Discovery of Association between Flow Cytometry Data and Clinical Endpoints

    Directory of Open Access Journals (Sweden)

    M. Eliot

    2009-01-01

    Full Text Available We demonstrate the application and comparative interpretations of three tree-based algorithms for the analysis of data arising from flow cytometry: classification and regression trees (CARTs, random forests (RFs, and logic regression (LR. Specifically, we consider the question of what best predicts CD4 T-cell recovery in HIV-1 infected persons starting antiretroviral therapy with CD4 count between 200 and 350 cell/μL. A comparison to a more standard contingency table analysis is provided. While contingency table analysis and RFs provide information on the importance of each potential predictor variable, CART and LR offer additional insight into the combinations of variables that together are predictive of the outcome. In all cases considered, baseline CD3-DR-CD56+CD16+ emerges as an important predictor variable, while the tree-based approaches identify additional variables as potentially informative. Application of tree-based methods to our data suggests that a combination of baseline immune activation states, with emphasis on CD8 T-cell activation, may be a better predictor than any single T-cell/innate cell subset analyzed. Taken together, we show that tree-based methods can be successfully applied to flow cytometry data to better inform and discover associations that may not emerge in the context of a univariate analysis.

  13. A novel endpoint for the assessment of chemotherapy-induced peripheral neuropathy in rodents: biomechanical properties of peripheral nerve.

    Science.gov (United States)

    Liu, Chang-Ning; Berryman, Edwin; Zakur, David; Shoieb, Ahmed M; Pardo, Ingrid D; Boucher, Magalie; Somps, Chris J; Bagi, Chedo M; Cook, Jon C

    2018-02-01

    Chemotherapy-induced peripheral neuropathy (CiPN) is a frequent adverse effect in patients and a leading safety consideration in oncology drug development. Although behavioral assessment and microscopic examination of the nerves and dorsal root ganglia can be incorporated into toxicity studies to assess CiPN risk, more sensitive and less labor-intensive endpoints are often lacking. In this study, rats and mice administered vincristine (75 μg kg-1  day-1 , i.p., for 10 days in rats and 100 μg kg-1  day-1 , i.p., for 11 days in mice, respectively) were employed as the CiPN models. Behavioral changes were assessed during the dosing phase. At necropsy, the sural or sciatic nerve was harvested from the rats and mice, respectively, and assessed for mechanical and histopathological endpoints. It was found that the maximal load and the load/extension ratio were significantly decreased in the nerves collected from the animals dosed with vincristine compared with the vehicle-treated animals (P < 0.05). Additionally, the gait analysis revealed that the paw print areas were significantly increased in mice (P < 0.01), but not in rats following vincristine administration. Light microscopic histopathology of the nerves and dorsal root ganglia were unaffected by vincristine administration. We concluded that ex vivo mechanical properties of the nerves is a sensitive endpoint, providing a new method to predict CiPN in rodent. Gait analysis may also be a useful tool in these pre-clinical animal models. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Understanding the role of peer group membership in reducing HIV-related risk and vulnerability among female sex workers in Karnataka, India.

    Science.gov (United States)

    Bhattacharjee, Parinita; Prakash, Ravi; Pillai, Priya; Isac, Shajy; Haranahalli, Mohan; Blanchard, Andrea; Shahmanesh, Maryam; Blanchard, James; Moses, Stephen

    2013-01-01

    In Karnataka state, South India, we analyzed the role of membership in peer groups in reducing HIV-related risk and vulnerability among female sex workers (FSWs). Data from three surveys conducted in Karnataka, a behavioral tracking survey and two rounds of integrated biological and behavioral assessments (IBBAs), were analyzed. Using propensity score matching, we examined the impact of group membership on selected outcomes, including condom use, experience of violence, access to entitlements, and the prevalence of sexually transmitted infections, including HIV infection. Focus group discussions were conducted with the FSWs to better understand their perceptions regarding membership in peer groups. Peer group members participating in the IBBAs had a lower prevalence of gonorrhea and/or chlamydia (5.2 vs 9.6%, ppeer group reported significantly less experience of violence in the past six months, were less likely to have bribed police to avoid trouble in the past six months, and were more likely to have obtained at least one formal identification document in the past five years, compared to non-members. In focus group discussions, group members indicated that they had more confidence in dealing with situations of forced sex and violence. Including community mobilization and peer group formation in the context of HIV prevention programing can reduce HIV-related risk and vulnerability among FSWs.

  15. A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi

    Directory of Open Access Journals (Sweden)

    H. Francis

    2012-01-01

    Full Text Available Background. Human-Immunodeficiency-Virus- (HIV- related Kaposi's sarcoma (KS has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA Palliative Outcome Scale (POS. Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial.

  16. Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal.

    Science.gov (United States)

    Rodríguez-Perálvarez, Manuel; Rico-Juri, Jose M; Tsochatzis, Emmanuel; Burra, Patrizia; De la Mata, Manuel; Lerut, Jan

    2016-09-01

    Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role. © 2015 Steunstichting ESOT.

  17. SU-D-204-01: A Methodology Based On Machine Learning and Quantum Clustering to Predict Lung SBRT Dosimetric Endpoints From Patient Specific Anatomic Features

    Energy Technology Data Exchange (ETDEWEB)

    Lafata, K; Ren, L; Wu, Q; Kelsey, C; Hong, J; Cai, J; Yin, F [Duke University Medical Center, Durham, NC (United States)

    2016-06-15

    Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space to identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong

  18. A Moderated Mediation Model of HIV-Related Stigma, Depression, and Social Support on Health-Related Quality of Life among Incarcerated Malaysian Men with HIV and Opioid Dependence.

    Science.gov (United States)

    Shrestha, Roman; Copenhaver, Michael; Bazazi, Alexander R; Huedo-Medina, Tania B; Krishnan, Archana; Altice, Frederick L

    2017-04-01

    Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support. Incarcerated HIV-infected men with opioid dependence (N = 301) were recruited from the HIV units in Kajang prison in Malaysia. Participants completed surveys assessing demographic characteristics, HIV-related stigma, depression, social support, and HRQoL. Results showed that the effect of HIV-related stigma on HRQoL was mediated via depression (a1:β = 0.1463, p stigma and depression was negatively associated with HRQOL (β = -0.0317, p = 0.0133). This indicated that the predicted influence of HIV-related stigma on HRQoL via depression had negative effect on HRQoL for individuals with low social support. The results suggest that social support can buffer the negative impact of depression on HRQoL and highlights the need for future interventions to target these psychosocial factors in order to improve HRQoL among incarcerated PLH.

  19. A DAG-based comparison of interventional effect underestimation between composite endpoint and multi-state analysis in cardiovascular trials

    Directory of Open Access Journals (Sweden)

    Antje Jahn-Eimermacher

    2017-07-01

    Full Text Available Abstract Background Composite endpoints comprising hospital admissions and death are the primary outcome in many cardiovascular clinical trials. For statistical analysis, a Cox proportional hazards model for the time to first event is commonly applied. There is an ongoing debate on whether multiple episodes per individual should be incorporated into the primary analysis. While the advantages in terms of power are readily apparent, potential biases have been mostly overlooked so far. Methods Motivated by a randomized controlled clinical trial in heart failure patients, we use directed acyclic graphs (DAG to investigate potential sources of bias in treatment effect estimates, depending on whether only the first or multiple episodes are considered. The biases first are explained in simplified examples and then more thoroughly investigated in simulation studies that mimic realistic patterns. Results Particularly the Cox model is prone to potentially severe selection bias and direct effect bias, resulting in underestimation when restricting the analysis to first events. We find that both kinds of bias can simultaneously be reduced by adequately incorporating recurrent events into the analysis model. Correspondingly, we point out appropriate proportional hazards-based multi-state models for decreasing bias and increasing power when analyzing multiple-episode composite endpoints in randomized clinical trials. Conclusions Incorporating multiple episodes per individual into the primary analysis can reduce the bias of a treatment’s total effect estimate. Our findings will help to move beyond the paradigm of considering first events only for approaches that use more information from the trial and augment interpretability, as has been called for in cardiovascular research.

  20. Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

    Science.gov (United States)

    Zakour, Sihem Ben; Taleb, Hassen

    2017-02-01

    Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

  1. Arsenate (As V) in water: quantitative sensitivity relationships among biomarker, ecotoxicity and genotoxicity endpoints.

    Science.gov (United States)

    Silva, Valéria C; Almeida, Sônia M; Resgalla, Charrid; Masfaraud, Jean-François; Cotelle, Sylvie; Radetski, Claudemir M

    2013-06-01

    It is useful to test ecotoxicity and genotoxicity endpoints in the environmental impact assessment. Here, we compare and discuss ecotoxicity and genotoxicity effects in organisms in response to exposure to arsenate (As V) in solution. Eco(geno)toxicity responses in Aliivibrio fischeri, Lytechinus variegatus, Daphnia magna, Skeletonema costatum and Vicia faba were analyzed by assessing different endpoints: biomass growth, peroxidase activity, mitotic index, micronucleus frequency, and lethality in accordance with the international protocols. Quantitative sensitivity relationships (QSR) between these endpoints were established in order to rank endpoint sensitivity. The results for the QSR values based on the lowest observed effect concentration (LOEC) ratios varied from 2 (for ratio of root peroxidase activity to leaf peroxidase activity) to 2286 (for ratio of higher plant biomass growth to root peroxidase activity). The QSR values allowed the following sensitivity ranking to be established: higher plant enzymatic activity>daphnids≈echinoderms>bacteria≈algae>higher plant biomass growth. The LOEC values for the mitotic index and micronucleus frequency (LOEC=0.25mgAsL(-1)) were similar to the lowest LOEC values observed in aquatic organisms. This approach to the QSR of different endpoints could form the basis for monitoring and predicting early effects of pollutants before they give rise to significant changes in natural community structures. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Population growth rate determinants for Arbacia: Evaluating ecological relevance of toxicity test endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Nacci, D.; Gleason, T.; Munns, W.R. Jr. [Environmental Protection Agency, Narragansett, RI (United States). Environmental Research Lab.

    1995-12-31

    A population dynamics model for the sea urchin, Arbacia punctulata, was recently developed incorporating life stage endpoints frequently measured in acute and chronic toxicity studies. Model elasticity analysis was used to demonstrate that population growth rate was influenced most by adult survival and least by early life stage success, calling into question the ecological relevance of results from standardized Arbacia fertilization and larval development toxicity tests. Two approaches were used to continue this evaluation. Actual and hypothetical dose-response curves for toxicant exposures over multiple life stages were used to evaluate contributions to population growth rate of stage-specific toxicant effects. Additionally, relationships between critical life stages were developed from laboratory data for Arbacia. The results of this analysis underscore the importance of understanding both endpoint sensitivity to toxicants and sensitivity of population growth rate to test endpoints in determining the ecological relevance of toxicity tests results.

  3. Meeting report: Measuring endocrine-sensitive endpoints within the first years of life

    DEFF Research Database (Denmark)

    Arbuckle, T.E.; Hauser, R.; Swan, S.H.

    2008-01-01

    An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine......-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove...... on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions....

  4. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    Science.gov (United States)

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Changing use of traditional healthcare amongst those dying of HIV related disease and TB in rural South Africa from 2003 - 2011: a retrospective cohort study.

    Science.gov (United States)

    Mee, Paul; Wagner, Ryan G; Gómez-Olivé, Francesc Xavier; Kabudula, Chodziwadziwa; Kahn, Kathleen; Madhavan, Sangeetha; Collinson, Mark; Byass, Peter; Tollman, Stephen M

    2014-12-17

    In 2011 there were 5.5 million HIV infected people in South Africa and 71% of those requiring antiretroviral therapy (ART) received it. The effective integration of traditional medical practitioners and biomedical providers in HIV prevention and care has been demonstrated. However concerns remain that the use of traditional treatments for HIV-related disease may lead to pharmacokinetic interactions between herbal remedies and ART drugs and delay ART initiation. Here we analyse the changing prevalence and determinants of traditional healthcare use amongst those dying of HIV-related disease, pulmonary tuberculosis and other causes in a rural South African community between 2003 and 2011. ART was made available in this area in the latter part of this period. Data was collected during household visits and verbal autopsy interviews. InterVA-4 was used to assign causes of death. Spatial analyses of the distribution of traditional healthcare use were performed. Logistic regression models were developed to test associations of determinants with traditional healthcare use. There were 5929 deaths in the study population of which 47.7% were caused by HIV-related disease or pulmonary tuberculosis (HIV/AIDS and TB). Traditional healthcare use declined for all deaths, with higher levels throughout for those dying of HIV/AIDS and TB than for those dying of other causes. In 2003-2005, sole use of biomedical treatment was reported for 18.2% of HIV/AIDS and TB deaths and 27.2% of other deaths, by 2008-2011 the figures were 49.9% and 45.3% respectively. In bivariate analyses, higher traditional healthcare use was associated with Mozambican origin, lower education levels, death in 2003-2005 compared to the later time periods, longer illness duration and moderate increases in prior household mortality. In the multivariate model only country of origin, time period and illness duration remained associated. There were large decreases in reported traditional healthcare use and increases in

  6. High heterogeneity of HIV-related sexual risk among transgender people in Ontario, Canada: a province-wide respondent-driven sampling survey

    Directory of Open Access Journals (Sweden)

    Bauer Greta R

    2012-04-01

    Full Text Available Abstract Background Studies of HIV-related risk in trans (transgender, transsexual, or transitioned people have most often involved urban convenience samples of those on the male-to-female (MTF spectrum. Studies have detected high prevalences of HIV-related risk behaviours, self-reported HIV, and HIV seropositivity. Methods The Trans PULSE Project conducted a multi-mode survey using respondent-driven sampling to recruit 433 trans people in Ontario, Canada. Weighted estimates were calculated for HIV-related risk behaviours, HIV testing and self-reported HIV, including subgroup estimates for gender spectrum and ethno-racial groups. Results Trans people in Ontario report a wide range of sexual behaviours with a full range of partner types. High proportions – 25% of female-to-male (FTM and 51% of MTF individuals – had not had a sex partner within the past year. Of MTFs, 19% had a past-year high-risk sexual experience, versus 7% of FTMs. The largest behavioural contributors to HIV risk were sexual behaviours some may assume trans people do not engage in: unprotected receptive genital sex for FTMs and insertive genital sex for MTFs. Overall, 46% had never been tested for HIV; lifetime testing was highest in Aboriginal trans people and lowest among non-Aboriginal racialized people. Approximately 15% of both FTM and MTF participants had engaged in sex work or exchange sex and about 2% currently work in the sex trade. Self-report of HIV prevalence was 10 times the estimated baseline prevalence for Ontario. However, given wide confidence intervals and the high proportion of trans people who had never been tested for HIV, estimating the actual prevalence was not possible. Conclusions Results suggest potentially higher than baseline levels of HIV; however low testing rates were observed and self-reported prevalences likely underestimate seroprevalence. Explicit inclusion of trans people in epidemiological surveillance statistics would provide much

  7. A brief, standardized tool for measuring HIV-related stigma among health facility staff: results of field testing in China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis.

    Science.gov (United States)

    Nyblade, Laura; Jain, Aparna; Benkirane, Manal; Li, Li; Lohiniva, Anna-Leena; McLean, Roger; Turan, Janet M; Varas-Díaz, Nelson; Cintrón-Bou, Francheska; Guan, Jihui; Kwena, Zachary; Thomas, Wendell

    2013-11-13

    Within healthcare settings, HIV-related stigma is a recognized barrier to access of HIV prevention and treatment services and yet, few efforts have been made to scale-up stigma reduction programs in service delivery. This is in part due to the lack of a brief, simple, standardized tool for measuring stigma among all levels of health facility staff that works across diverse HIV prevalence, language and healthcare settings. In response, an international consortium led by the Health Policy Project, has developed and field tested a stigma measurement tool for use with health facility staff. Experts participated in a content-development workshop to review an item pool of existing measures, identify gaps and prioritize questions. The resulting questionnaire was field tested in six diverse sites (China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis). Respondents included clinical and non-clinical staff. Questionnaires were self- or interviewer-administered. Analysis of item performance across sites examined both psychometric properties and contextual issues. The key outcome of the process was a substantially reduced questionnaire. Eighteen core questions measure three programmatically actionable drivers of stigma within health facilities (worry about HIV transmission, attitudes towards people living with HIV (PLHIV), and health facility environment, including policies), and enacted stigma. The questionnaire also includes one short scale for attitudes towards PLHIV (5-item scale, α=0.78). Stigma-reduction programmes in healthcare facilities are urgently needed to improve the quality of care provided, uphold the human right to healthcare, increase access to health services, and maximize investments in HIV prevention and treatment. This brief, standardized tool will facilitate inclusion of stigma measurement in research studies and in routine facility data collection, allowing for the monitoring of stigma within healthcare facilities and evaluation of

  8. A brief, standardized tool for measuring HIV-related stigma among health facility staff: results of field testing in China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis

    Science.gov (United States)

    Nyblade, Laura; Jain, Aparna; Benkirane, Manal; Li, Li; Lohiniva, Anna-Leena; McLean, Roger; Turan, Janet M; Varas-Díaz, Nelson; Cintrón-Bou, Francheska; Guan, Jihui; Kwena, Zachary; Thomas, Wendell

    2013-01-01

    Introduction Within healthcare settings, HIV-related stigma is a recognized barrier to access of HIV prevention and treatment services and yet, few efforts have been made to scale-up stigma reduction programs in service delivery. This is in part due to the lack of a brief, simple, standardized tool for measuring stigma among all levels of health facility staff that works across diverse HIV prevalence, language and healthcare settings. In response, an international consortium led by the Health Policy Project, has developed and field tested a stigma measurement tool for use with health facility staff. Methods Experts participated in a content-development workshop to review an item pool of existing measures, identify gaps and prioritize questions. The resulting questionnaire was field tested in six diverse sites (China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis). Respondents included clinical and non-clinical staff. Questionnaires were self- or interviewer-administered. Analysis of item performance across sites examined both psychometric properties and contextual issues. Results The key outcome of the process was a substantially reduced questionnaire. Eighteen core questions measure three programmatically actionable drivers of stigma within health facilities (worry about HIV transmission, attitudes towards people living with HIV (PLHIV), and health facility environment, including policies), and enacted stigma. The questionnaire also includes one short scale for attitudes towards PLHIV (5-item scale, α = 0.78). Conclusions Stigma-reduction programmes in healthcare facilities are urgently needed to improve the quality of care provided, uphold the human right to healthcare, increase access to health services, and maximize investments in HIV prevention and treatment. This brief, standardized tool will facilitate inclusion of stigma measurement in research studies and in routine facility data collection, allowing for the monitoring of stigma within

  9. Right-handed currents at B→ {K^{*}}ℓ ^+ℓ - kinematic endpoint

    Science.gov (United States)

    Mandal, Rusa; Karan, Anirban; Nayak, Abinash Kumar; Sinha, Rahul; Browder, Tom

    2017-10-01

    The rare decay B→ {K^{*}}ℓ ^+ℓ ^- is a very significant mode to search for physics beyond the Standard Model (SM). The mode provides a very rich spectrum of observables obtained from the angular distribution of its decay products. The recent LHCb measured values of these observables are used to conclude an evidence of right-handed currents at the kinematic endpoint of this decay mode. As the conclusion is drawn at the maximum dilepton invariant mass square (q^2) kinematic endpoint, it relies only on heavy quark symmetries where it is valid without significant corrections.

  10. A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

    Science.gov (United States)

    Benacer, Douadi; Zain, Siti Nursheena Mohd; Lewis, John W; Khalid, Mohd Khairul Nizam Mohd; Thong, Kwai Lin

    2017-01-01

    This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains. Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively. The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.1pg/µl of leptospiral DNA and sensitivity of 103 leptospires/ml in both spiked urine and water. Our duplex endpoint PCR assay is suitable for rapid early detection of Leptospira with high sensitivity and specificity.

  11. Automated Assessment of Endpoint and Kinematic Features of Skilled Reaching in Rats

    Directory of Open Access Journals (Sweden)

    Ioana Nica

    2018-01-01

    Full Text Available Background: Neural injury to the motor cortex may result in long-term impairments. As a model for human impairments, rodents are often used to study deficits related to reaching and grasping, using the single-pellet reach-to-grasp task. Current assessments of this test capture mostly endpoint outcome. While qualitative features have been proposed, they usually involve manual scoring.Objective: To detect three phases of movement during the single-pellet reach-to-grasp test and assess completion of each phase. To automatically monitor rat forelimb trajectory so as to extract kinematics and classify phase outcome.Methods: A top-view camera is used to monitor three rats during training, healthy and impaired testing, over 33 days. By monitoring the coordinates of the forelimb tip along with the position of the pellet, the algorithm divides a trial into reaching, grasping and retraction. Unfulfilling any of the phases results in one of three possible errors: miss, slip or drop. If all phases are complete, the outcome label is success. Along with endpoints, movement kinematics are assessed: variability, convex hull, mean and maximum reaching speed, length of trajectory and peak forelimb extension.Results: The set of behavior endpoints was extended to include miss, slip, drop and success rate. The labeling algorithm was tested on pre- and post-lesion datasets, with overall accuracy rates of 86% and 92%, respectively. These endpoint features capture a drop in skill after motor cortical lesion as the success rate of 59.6 ± 11.8% pre-lesion decreases to 13.9 ± 8.2% post-lesion, along with a significant increase in miss rate from 7.2 ± 6.7% pre-lesion to 50.2 ± 18.7% post-lesion. Kinematics reveals individual-specific strategies of improvement during training, with a common trend of trajectory variability decreasing with success. Correlations between kinematics and endpoints reveal a more complex pattern of relationships during rehabilitation (18

  12. The influence of having children on HIV-related risk behaviors of female sex workers and their intimate male partners in two Mexico-US border cities.

    Science.gov (United States)

    Rolon, Maria Luisa; Syvertsen, Jennifer L; Robertson, Angela M; Rangel, M Gudelia; Martinez, Gustavo; Ulibarri, Monica D; Servin, Argentina; Strathdee, Steffanie A

    2013-06-01

    Among female sex workers who use drugs, the experience of having children and its effect on HIV risk behaviors remains underexplored. We draw from a study of 214 female sex workers and their intimate non-commercial partners in Tijuana and Ciudad Juárez, México (n = 428), approximately 30% of whom have children living with them. During qualitative interviews with 41 of these couples, having children emerged as an important topic. Children influenced partners' lives and HIV-related risk behaviors in positive and negative ways. Couples perceived that children strengthened their relationships. Concern for children's well-being motivated couples to contemplate healthier lifestyle changes. However, childrearing costs motivated sex work and structural constraints prevented couples from enacting lifestyle changes. Case studies illustrate these themes and highlight implications for couple- and family-based harm reduction interventions. Specifically, our results suggest a need for economic alternatives to sex work while working with families to develop risk reduction skills.

  13. Identifying Strategies to Cope with HIV-Related Stigma in a Group of Women Living with HIV/AIDS in the Dominican Republic: A Qualitative Study.

    Science.gov (United States)

    Rael, Christine Tagliaferri; Carballo-Diéguez, Alex; Norton, Rachel; Thorley, Eryka; Giguere, Rebecca; Sheinfil, Alan; Rios, Javier López

    2016-12-20

    Internalized HIV-related stigma negatively impacts the mental and physical health of women living with HIV/AIDS (WLWHA). Yet, some women can successfully confront stigma. The present work uses qualitative methods to investigate the successful stigma coping strategies displayed by 19 WLWHA who reported the least internalized stigma possible on the Internalized AIDS-Related Stigma Scale out of a larger pool of 233 WLWHA in San Felipe de Puerto Plata, Dominican Republic. Such strategies included, HIV disclosure control; preemptive disclosure of HIV-status; educating oneself/others about HIV; viewing HIV as a manageable condition; and looking to family, friends and partners for support. Our findings add to current knowledge about how WLWHA successfully manage internalized stigma, particularly in the context of the Dominican Republic. Clinicians should work closely with WLWHA to counsel them about the stigma coping strategies that best fit their life context.

  14. "Inside These Fences Is Our Own Little World": Prison-Based HIV Testing and HIV-Related Stigma Among Incarcerated Men and Women.

    Science.gov (United States)

    Muessig, Kathryn E; Rosen, David L; Farel, Claire E; White, Becky L; Filene, Eliza J; Wohl, David A

    2016-04-01

    Correctional facilities offer opportunities to provide comprehensive HIV services including education, testing, treatment, and coordination of post- release care. However, these services may be undermined by unaddressed HIV stigma. As part of a prison-based HIV testing study, we interviewed 76 incarcerated men and women from the North Carolina State prison system. The sample was 72% men, median age 31.5 years (range: 19 to 60). Thematic analysis revealed high levels of HIV-related fear and stigma, homophobia, incomplete HIV transmission knowledge, beliefs that HIV is highly contagious within prisons ("HIV miasma"), and the View of HIV testing as protective. Interviewees described social distancing behaviors and coping mechanisms they perceived to be protective, including knowing their HIV status and avoiding contact with others and shared objects. Interviewees endorsed universal testing, public HIV status disclosure, and segregation of HIV-positive inmates. Intensified education and counseling efforts are needed to ameliorate entrenched HIV-transmission fears and stigmatizing beliefs.

  15. A narrative analysis positioning HIV relative to personal (sexual) relationship challenges in an agony aunt column in the Western Cape, South Africa - Aunty Mona's "love advice".

    Science.gov (United States)

    Viljoen, Lario; Thorne, Marguerite; Thomas, Angelique; Bond, Virginia; Hoddinott, Graeme

    2016-01-01

    HIV prevalence and incidence in South Africa remain high, making HIV a part of everyday life. Community narratives on HIV treatment and prevention are important and influence official and unofficial health messaging and community perceptions and understandings of HIV. We explore how contributors and the columnist of an agony aunt column position HIV relative to choices made about love, partnership, and sex over three years. We analysed all columns of an agony aunt series (Antie Mona) published between December 2012 and November 2015. The column is published in a South African, Afrikaans-language newspaper "Son", prioritising sensationalist news items. Trends were identified through narrative analysis. Data were managed in ATLAS.ti and inductive, iterative coding conducted. It was found that letters to the agony aunt rarely refer to HIV directly (less than 7%). Euphemisms such as diseases of the flesh and the great flu were more commonly used instead of HIV or AIDS. Letters addressed HIV in three ways: direct references to experiences living with HIV; direct questions about HIV prevention; and scenarios where HIV could (from a public health perspective) have been the main concern, but everyday issues took precedence. The majority of letters fell into this latter category where the writers focused on the immediate concerns of good sexual relations, problems related to love and romantic relationships, good moral behaviour of others, and issues of oppressive life conditions rather than on HIV directly. The findings illustrate that informal, public contributions to health information, such as agony aunts, are important narratives that inform popular perspectives on HIV and health. A better appreciation of this context would allow health implementers to ensure that these role players receive updated health messaging to avoid the risk of HIV-related stigma where HIV is used as a moral rod to punish perceived moral transgressions.

  16. Adaptation and Implementation of an Intervention to Reduce HIV-Related Stigma Among Healthcare Workers in the United States: Piloting of the FRESH Workshop.

    Science.gov (United States)

    Batey, D Scott; Whitfield, Samantha; Mulla, Mazheruddin; Stringer, Kristi L; Durojaiye, Modupeoluwa; McCormick, Lisa; Turan, Bulent; Nyblade, Laura; Kempf, Mirjam-Colette; Turan, Janet M

    2016-11-01

    HIV-related stigma has been shown to have profound effects on people living with HIV (PLWH). When stigma is experienced in a healthcare setting, negative health outcomes are exacerbated. We sought to assess the feasibility and acceptability of a healthcare setting stigma-reduction intervention, the Finding Respect and Ending Stigma around HIV (FRESH) Workshop, in the United States. This intervention, adapted from a similar strategy implemented in Africa, brought together healthcare workers (HW) and PLWH to address HIV-related stigma. Two pilot workshops were conducted in Alabama and included 17 HW and 19 PLWH. Participants completed questionnaire measures pre- and post-workshop, including open-ended feedback items. Analytical methods included assessment of measures reliability, pre-post-test comparisons using paired t-tests, and qualitative content analysis. Overall satisfaction with the workshop experience was high, with 87% PLWH and 89% HW rating the workshop "excellent" and the majority agreeing that others like themselves would be interested in participating. Content analysis of open-ended items revealed that participants considered the workshop informative, interactive, well-organized, understandable, fun, and inclusive, while addressing real and prevalent issues. Most pre- and post-test measures had good-excellent internal consistency reliability (Cronbach's alphas ranging from 0.70 to 0.96) and, although sample sizes were small, positive trends were observed, reaching statistical significance for increased awareness of stigma in the health facility among HW (p = 0.047) and decreased uncertainty about HIV treatment among PLWH (p = 0.017). The FRESH intervention appears to be feasible and highly acceptable to HW and PLWH participants and shows great promise as a healthcare setting stigma-reduction intervention for US contexts.

  17. Drop-out from cardiovascular magnetic resonance in a randomized controlled trial of ST-elevation myocardial infarction does not cause selection bias on endpoints.

    Science.gov (United States)

    Laursen, Peter Nørkjær; Holmvang, L; Kelbæk, H; Vejlstrup, N; Engstrøm, T; Lønborg, J

    2017-07-01

    The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before acute CMR assessment compared to CMR-participants in a previously published double-blinded, placebo-controlled all-comer trial with CMR outcome as the primary endpoint. Baseline characteristics and composite endpoint of all-cause mortality, heart failure and re-infarction after 30 days and 5 years of follow-up were assessed and compared between CMR-drop-outs and CMR-participants using the trial screening log and the Eastern Danish Heart Registry. The drop-out rate from acute CMR was 28% (n = 92). These patients had a significantly worse clinical risk profile upon admission as evaluated by the TIMI-risk score (3.7 (± 2.1) vs 4.0 (± 2.6), p = 0.043) and by left ventricular ejection fraction (43 (± 9) vs. 47 (± 10), p = 0.029). CMR drop-outs had a higher incidence of known hypertension (39% vs. 35%, p = 0.043), known diabetes (14% vs. 7%, p = 0.025), known cardiac disease (11% vs. 3%, p = 0.013) and known renal function disease (5% vs. 0%, p = 0.007). However, the 30-day and 5-years composite endpoint rate was not significantly higher among the CMR drop-out ((HR 1.43 (95%-CI 0.5; 3.97) (p = 0.5)) and (HR 1.31 (95%-CI 0.84; 2.05) (p = 0.24)). CMR-drop-outs had a higher incidence of cardiovascular risk factors at baseline, a worse clinical risk profile upon admission. However, no significant difference was observed in the clinical endpoints between the groups.

  18. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  19. Recent Developments in Whole Sediment Toxicity Identification Evaluations: Innovations in Manipulations and Endpoints

    Science.gov (United States)

    Whole sediment Toxicity Identification Evaluation (TIE) methods were developed primarily in the late 1990s and early 2000s in research programs dedicated to developing manipulations and endpoints to characterize and identify causes of toxicity to benthic freshwater and marine org...

  20. Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints

    Science.gov (United States)

    Thompson, John R; Spata, Enti; Abrams, Keith R

    2015-01-01

    We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing–remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions. PMID:26271918

  1. Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

    NARCIS (Netherlands)

    Parving, Hans-Henrik; Brenner, Barry M.; McMurray, John J. V.; de Zeeuw, Dick; Haffner, Steven M.; Solomon, Scott D.; Chaturvedi, Nish; Persson, Frederik; Nicolaides, Maria; Richard, Alexia; Xiang, Zhihua; Armbrecht, Juergen; Pfeffer, Marc A.

    Introduction: Patients with type 2 diabetes are at enhanced risk for macro-and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel

  2. Coulometric Titration of Ethylenediaminetetraacetate (EDTA) with Spectrophotometric Endpoint Detection: An Experiment for the Instrumental Analysis Laboratory

    Science.gov (United States)

    Williams, Kathryn R.; Young, Vaneica Y.; Killian, Benjamin J.

    2011-01-01

    Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

  3. End-point construction and systematic titration error in linear titration curves-complexation reactions

    NARCIS (Netherlands)

    Coenegracht, P.M.J.; Duisenberg, A.J.M.

    The systematic titration error which is introduced by the intersection of tangents to hyperbolic titration curves is discussed. The effects of the apparent (conditional) formation constant, of the concentration of the unknown component and of the ranges used for the end-point construction are

  4. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups.

    Science.gov (United States)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives I Batlle, Jordi; Oughton, Deborah H; Garnier-Laplace, Jacqueline

    2016-02-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R0, asymptotic population growth rate λ, equilibrium population size Neq) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R0, λ or Neq) and the life history of the studied species. Among population endpoints, net reproductive rate R0 showed the lowest EDR10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h(-1) in the mouse Mus musculus to 38,000 μGy h(-1) in the fish Oryzias latipes. For several species, EDR10 for population endpoints were lower than the lowest EDR10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h(-1) in fish to 12,000 μGy h(-1) in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h(-1) in mammals to 1800 μGy h(-1) in

  5. The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2010-01-01

    OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

  6. Systematic Review and Meta-analysis of the Association Between Exposure to Environmental Tobacco Smoke and Periodontitis Endpoints Among Nonsmokers.

    Science.gov (United States)

    Akinkugbe, Aderonke A; Slade, Gary D; Divaris, Kimon; Poole, Charles

    2016-11-01

    A systematic review was conducted to summarize the epidemiological evidence on environmental tobacco smoke (ETS) exposure and prevalent periodontitis endpoints among nonsmokers. We searched PubMed, EMBASE, Web of Science, Pro-Quest dissertations, and conference proceedings of a dental research association. We included studies from which prevalence odds ratios (POR) could be extracted for periodontitis determined by examiner measurements of clinical attachment level (CAL) and/or probing pocket depth (PD) or self-report of missing teeth. Studies determined ETS exposure by self-report or biomarker (cotinine) levels. For studies reporting CAL and/or PD (n = 6), associations were stronger with cotinine-measured exposure (n = 3; random effects POR [95% prediction interval] = 1.63 (0.90, 2.96)) than self-reported exposure (n = 3; random effects POR = 1.15 (0.68, 1.96)). There was no meaningful difference in summary estimate for studies reporting CAL and/or PD endpoint (n = 6; random effects POR = 1.34 (0.93, 1.94)) as opposed to tooth loss (n = 2; random effects POR = 1.33 (0.52, 3.40)). There appears to be a positive association between exposure to ETS and prevalent periodontitis endpoints among nonsmokers, the magnitude of which depended mostly on the method of ETS assessment. The notoriety of ETS is often discussed in terms of its associations with cancer, chronic conditions like cardiovascular diseases, and respiratory illnesses in children. However, very little attention is paid to its association with oral diseases, especially periodontitis. Periodontitis affects a large proportion of the population and is a major cause of tooth loss. This study summarized the epidemiologic association between exposure to ETS and periodontitis among nonsmokers. Although the findings are consistent with a positive association, methodological weaknesses relating to study design, assessment of ETS, periodontitis, and adjustment covariates were highlighted and recommendations for

  7. Imputation of a true endpoint from a surrogate: application to a cluster randomized controlled trial with partial information on the true endpoint

    Directory of Open Access Journals (Sweden)

    Duffy Stephen W

    2003-09-01

    Full Text Available Abstract Background The Anglia Menorrhagia Education Study (AMES is a randomized controlled trial testing the effectiveness of an education package applied to general practices. Binary data are available from two sources; general practitioner reported referrals to hospital, and referrals to hospital determined by independent audit of the general practices. The former may be regarded as a surrogate for the latter, which is regarded as the true endpoint. Data are only available for the true end point on a sub set of the practices, but there are surrogate data for almost all of the audited practices and for most of the remaining practices. Methods The aim of this paper was to estimate the treatment effect using data from every practice in the study. Where the true endpoint was not available, it was estimated by three approaches, a regression method, multiple imputation and a full likelihood model. Results Including the surrogate data in the analysis yielded an estimate of the treatment effect which was more precise than an estimate gained from using the true end point data alone. Conclusions The full likelihood method provides a new imputation tool at the disposal of trials with surrogate data.

  8. Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda

    NARCIS (Netherlands)

    Ssengooba, Willy; Nakiyingi, Lydia; Armstrong, Derek T.; Cobelens, Frank G.; Alland, David; Manabe, Yukari C.; Dorman, Susan E.; Ellner, Jerrold J.; Joloba, Moses L.

    2014-01-01

    Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay (Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement strategy for pulmonary tuberculosis diagnosis among HIV-infected adults

  9. Current updates on HIV-related pulmonary disease in children: What do radiologists and clinicians need to know?

    Directory of Open Access Journals (Sweden)

    Tracy Kilborn

    2015-10-01

    Full Text Available Despite substantial advances in diagnosis and treatment, pulmonary human immunodeficiency virus (HIV infection continues to be a major cause of morbidity and mortality in infants and children particularly those who live in developing countries. This article provides an up-to-date review on underlying etiology, often characteristic imaging findings and current management of pulmonary HIV infection in infants and children. Increased understanding of clinical and unique imaging findings of pulmonary HIV infection has a great potential for early and accurate diagnosis which, in turn, can eventually improve pediatric patient care.

  10. Movement trajectory smoothness is not associated with the endpoint accuracy of rapid multi-joint arm movements in young and older adults.

    Science.gov (United States)

    Poston, Brach; Van Gemmert, Arend W A; Sharma, Siddharth; Chakrabarti, Somesh; Zavaremi, Shahrzad H; Stelmach, George

    2013-06-01

    The minimum variance theory proposes that motor commands are corrupted by signal-dependent noise and smooth trajectories with low noise levels are selected to minimize endpoint error and endpoint variability. The purpose of the study was to determine the contribution of trajectory smoothness to the endpoint accuracy and endpoint variability of rapid multi-joint arm movements. Young and older adults performed arm movements (4 blocks of 25 trials) as fast and as accurately as possible to a target with the right (dominant) arm. Endpoint accuracy and endpoint variability along with trajectory smoothness and error were quantified for each block of trials. Endpoint error and endpoint variance were greater in older adults compared with young adults, but decreased at a similar rate with practice for the two age groups. The greater endpoint error and endpoint variance exhibited by older adults were primarily due to impairments in movement extent control and not movement direction control. The normalized jerk was similar for the two age groups, but was not strongly associated with endpoint error or endpoint variance for either group. However, endpoint variance was strongly associated with endpoint error for both the young and older adults. Finally, trajectory error was similar for both groups and was weakly associated with endpoint error for the older adults. The findings are not consistent with the predictions of the minimum variance theory, but support and extend previous observations that movement trajectories and endpoints are planned independently. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Evidence for localised HIV related micro–epidemics associated with the decentralised provision of antiretroviral treatment in rural South Africa: a spatio–temporal analysis of changing mortality patterns (2007–2010

    Directory of Open Access Journals (Sweden)

    Paul Mee

    2014-06-01

    Full Text Available In this study we analysed the spatial and temporal changes in patterns of mortality over a period when antiretroviral therapy (ART was rolled out in a rural region of north–eastern South Africa. Previous studies have identified localised concentrated HIV related sub–epidemics and recommended that micro–level analyses be carried out in order to direct focused interventions.

  12. Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials

    Science.gov (United States)

    Gottlieb, Klaus; Dawson, Jill; Hussain, Fez; Murray, Joseph A.

    2015-01-01

    Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests. We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials, with a particular emphasis on current thinking in regulatory agencies. We conclude our paper with recommendations and a glossary of regulatory terms, to enable readers who are less familiar with regulatory language to take maximum advantage of this review. PMID:25725041

  13. Amplicon Competition Enables End-Point Quantitation of Nucleic Acids Following Isothermal Amplification.

    Science.gov (United States)

    Jiang, Yu Sherry; Stacy, Apollo; Whiteley, Marvin; Ellington, Andrew D; Bhadra, Sanchita

    2017-09-05

    It is inherently difficult to quantitate nucleic acid analytes with most isothermal amplification assays. We developed loop-mediated isothermal amplification (LAMP) reactions in which competition between defined numbers of "false" and "true" amplicons leads to order of magnitude quantitation by a single endpoint determination. These thresholded LAMP reactions were successfully used to directly and quantitatively estimate the numbers of nucleic acids in complex biospecimens, including directly from cells and in sewage, with the values obtained closely correlating with qPCR quantitations. Thresholded LAMP reactions are amenable to endpoint readout by cell phone, unlike other methods that require continuous monitoring, and should therefore prove extremely useful in developing one-pot reactions for point-of-care diagnostics without needing sophisticated material or informatics infrastructure. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

    Directory of Open Access Journals (Sweden)

    Federico Fogolari

    2018-02-01

    Full Text Available Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

  15. A versatile adaptive dose-finding design based on multiple endpoints

    DEFF Research Database (Denmark)

    Baayen, Corine; Hougaard, Philip; Pipper, C. B.

    2017-01-01

    depends on the unknown model parameters. A solution is to use adaptive designs. Ideally, such procedures evaluate a safety and an efficacy endpoint to get the best understanding of the therapeutic window. Many such designs have already been proposed. However, the outcomes are typically required...... to be of a specific type and the correlation between them has to be modeled explicitly. We propose a more general and simpler approach. Separate models can be specified for each endpoint, without restrictions on the type of model or outcome. The dependence between the outcomes is considered, without having to specify...... its structure. A new penalty function is introduced to balance the need for optimal precision and safe dose assignments. The method is illustrated by an example study in depression. Simulation results indicate that the adaptive design is more efficient than a fixed design. Use of the penalty function...

  16. Motor Power Signal Analysis for End-Point Detection of Chemical Mechanical Planarization

    Directory of Open Access Journals (Sweden)

    Hongkai Li

    2017-06-01

    Full Text Available In the integrated circuit (IC manufacturing, in-situ end-point detection (EPD is an important issue in the chemical mechanical planarization (CMP process. In the paper, we chose the motor power signal of the polishing platen as the monitoring object. We then used the moving average method, which was appropriate for in-situ calculation process and made it easy to code for software development, to smooth the signal curve, and then studied the signal variation during the actual CMP process. The results demonstrated that the motor power signal contained the end-point feature of the metal layer removal, and the processed signal curve facilitated the feature extraction and it was relatively steady before and after the layer transition stage. In addition, the motor power signal variation of the polishing head was explored and further analysis of time delay was performed.

  17. The impact of SASA!, a community mobilization intervention, on reported HIV-related risk behaviours and relationship dynamics in Kampala, Uganda.

    Science.gov (United States)

    Kyegombe, Nambusi; Abramsky, Tanya; Devries, Karen M; Starmann, Elizabeth; Michau, Lori; Nakuti, Janet; Musuya, Tina; Heise, Lori; Watts, Charlotte

    2014-01-01

    Intimate partner violence (IPV) violates women's human rights, and it is a serious public health concern associated with increased HIV risk. SASA!, a phased community mobilization intervention, engages communities to prevent IPV and promote gender equity. The SASA! study assessed the community-level impact of SASA! on reported HIV-related risk behaviours and relationship dynamics. Data were collected as part of a cluster randomized controlled trial conducted between 2007 and 2012 in eight communities in Kampala. An adjusted cluster-level intention to treat analysis, compares secondary outcomes in intervention and control communities at follow-up. The qualitative evaluation explored participants' subjective experience of SASA!. A total of 82 in-depth interviews were audio recorded at follow-up, transcribed verbatim and analyzed using thematic analysis. Men in intervention communities were significantly more likely than controls to report a broad range of HIV-protective behaviours, including higher levels of condom use (aRR 2.03, 95% CI 1.22-3.39), HIV testing (aRR 1.50, 95% CI 1.13-2.00) and fewer concurrent partners (aRR 0.60, 95% CI 0.37-0.97). They were also more likely to report increased joint decision-making (aRR 1.92, 95% CI 1.27-2.91), greater male participation in household tasks (aRR 1.48, 95% CI 1.09-2.01), more open communication and greater appreciation of their partner's work inside (aRR 1.31, 95% CI 1.04-1.66) and outside (aRR 1.49, 95% CI 1.08-2.06) the home. For women, all outcomes were in the hypothesized direction, but effect sizes were smaller. Only some achieved statistical significance. Women in intervention communities were significantly more likely to report being able to refuse sex with their partners (aRR 1.16, 95% CI 1.00-1.35), joint decision-making (aRR 1.37, 95% CI 1.06-1.78) and more open communication on a number of indicators. Qualitative interviews suggest that shifts operated through broader improvements in relationships, including

  18. A pilot study of cognitive training with and without transcranial direct current stimulation to improve cognition in older persons with HIV-related cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ownby RL

    2016-10-01

    Full Text Available Raymond L Ownby,1 Amarilis Acevedo2 1Department of Psychiatry and Behavioral Medicine, 2College of Psychology, Nova Southeastern University, Fort Lauderdale, FL, USA Background: In spite of treatment advances, HIV infection is associated with cognitive deficits. This is even more important as many persons with HIV infection age and experience age-related cognitive impairments. Both computer-based cognitive training and transcranial direct current stimulation (tDCS have shown promise as interventions to improve cognitive function. In this study, we investigate the acceptability and efficacy of cognitive training with and without tDCS in older persons with HIV. Patients and methods: In this single-blind randomized study, participants were 14 individuals of whom 11 completed study procedures (mean age =51.5 years; nine men and two women with HIV-related mild neurocognitive disorder. Participants completed a battery of neuropsychological and self-report measures and then six 20-minute cognitive training sessions while receiving either active or sham anodal tDCS over the left dorsolateral prefrontal cortex. After training, participants completed the same measures. Success of the blind and participant reactions were assessed during a final interview. Assessments were completed by an assessor blind to treatment assignment. Pre- and post-training changes were evaluated via analysis of covariance yielding estimates of effect size. Results: All participants believed that they had been assigned to active treatment; nine of the 11 believed that the intervention had improved their cognitive functioning. Both participants who felt the intervention was ineffective were assigned to the sham condition. None of the planned tested interactions of time with treatment was significant, but 12 of 13 favored tDCS (P=0.08. All participants indicated that they would participate in similar studies in the future. Conclusion: Results show that both cognitive training via

  19. A systematic review of interventions to reduce HIV-related stigma and discrimination from 2002 to 2013: how far have we come?

    Science.gov (United States)

    Stangl, Anne L; Lloyd, Jennifer K; Brady, Laura M; Holland, Claire E; Baral, Stefan

    2013-11-13

    HIV-related stigma and discrimination continue to hamper efforts to prevent new infections and engage people in HIV treatment, care and support programmes. The identification of effective interventions to reduce stigma and discrimination that can be integrated into national responses is crucial to the success of the global AIDS response. We conducted a systematic review of studies and reports that assessed the effectiveness of interventions to reduce HIV stigma and discrimination between 1 January 2002 and 1 March 2013. Databases searched for peer-reviewed articles included PubMed, Scopus, EBSCO Host -CINAHL Plus, Psycinfo, Ovid, Sociofile and Popline. Reports were obtained from the www.HIVAIDSClearinghouse.eu, USAID Development Experience Clearinghouse, UNESCO HIV and AIDS Education Clearinghouse, Google, WHO and UNAIDS. Ancestry searches for articles included in the systematic review were also conducted. Studies of any design that sought to reduce stigma as a primary or secondary objective and included pre- and post-intervention measures of stigma were included. Of 2368 peer-reviewed articles and reports identified, 48 were included in our review representing 14 different target populations in 28 countries. The majority of interventions utilized two or more strategies to reduce stigma and discrimination, and ten included structural or biomedical components. However, most interventions targeted a single socio-ecological level and a single domain of stigma. Outcome measures lacked uniformity and validity, making both interpretation and comparison of study results difficult. While the majority of studies were effective at reducing the aspects of stigma they measured, none assessed the influence of stigma or discrimination reduction on HIV-related health outcomes. Our review revealed considerable progress in the stigma-reduction field. However, critical challenges and gaps remain which are impeding the identification of effective stigma-reduction strategies that can

  20. Evidence of increased STI/HIV-related risk behavior among male perpetrators of intimate partner violence in Guatemala: results from a national survey.

    Science.gov (United States)

    Hembling, John; Andrinopoulos, Katherine

    2014-01-01

    Intimate partner violence (IPV) is a significant public health problem with a demonstrated link to increased sexually transmitted infection (STI)/HIV-related risk and vulnerability. While IPV is an important issue in Central America, the link to STI/HIV risk has not been explored in this region. In this study, the relationship between emotional and physical/sexual IPV and the STI/HIV-related risk behaviors of sex worker patronage and infidelity is assessed among male IPV perpetrators using data from a national survey conducted in 2009 in Guatemala (n = 4773 married/partnered men). Bivariate associations between background characteristics and emotional and physical IPV perpetration were explored. Logistic regression models were run to test associations between IPV for each sexual risk behavior. Perpetration of emotional and physical/sexual IPV was more common among married/partnered men who were older than 24, had more education, lived in urban areas, or were in common law versus married unions. Reports of past-year emotional IPV perpetration increased as wealth quintile increased. After adjusting for demographics and other characteristics, physical/sexual IPV perpetration was associated with past-year infidelity (AOR 1.9, 95% CI: 1.1-3.6). Lifetime emotional IPV (AOR 1.4, 95% CI: 1.1-1.7) and physical/sexual IPV 1.6 (95% CI 1.2-2.0) were positively associated with a history of sex worker patronage. Endorsement of traditional gender role norms showed a marginally positive association with past-year infidelity in the adjusted model (AOR 1.3, 95% CI 1.0-1.8). The study findings from Guatemala reinforce the growing evidence globally that male IPV perpetrators are more likely to engage in risky sexual behavior, including sex worker patronage and main partner infidelity. The concurrency of violence and increased STI/HIV risk may compound the health risks for female victims of IPV who also face injury and psychological trauma. Integration of prevention and screening of

  1. Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

    DEFF Research Database (Denmark)

    Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

    2012-01-01

    Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin...... inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone....

  2. Biomonitoring: Guide for the Use of Biological Endpoints in Monitoring Species, Habitats, and Projects

    Science.gov (United States)

    2007-11-01

    water and biota chemistry as well as amphipod and sea urchin toxicity testing during the first 5 years after the remedial action is completed. Since...change in presence, abundance, morphology , physiology, or behavior of the biomonitoring species is considered to indicate that one or more of its... morphological character, or survival) of the biomonitoring species that is measured during the biomonitoring program. Measured changes in the endpoint are

  3. Factors Influencing Depression Endpoints Research (FINDER: baseline results of Italian patients with depression

    Directory of Open Access Journals (Sweden)

    Grassi Luigi

    2009-05-01

    Full Text Available Abstract Background Factors Influencing Depression Endpoints Research (FINDER is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL in outpatients receiving pharmacological treatment for a first or new depressive episode. Baseline characteristics of patients enrolled in Italy are presented. Methods All treatment decisions were at the discretion of the investigator. Data were collected at baseline and after 3 and 6 months of treatment. Baseline evaluations included demographics, medical and psychiatric history, and medications used in the last 24 months and prescribed at enrolment. The Hospital Anxiety and Depression Scale (HADS, was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the Somatic Symptom Inventory (SSI and a 0 to 100 mm visual analogue scale (VAS, HRQoL via 36-item Short Form Health Survey (SF-36, and the European Quality of Life 5-Dimensions (EQ-5D instrument. Results A total of 513 patients were recruited across 38 sites. The mean ± standard deviation (SD age at first depressive episode was 38.7 ± 15.9 years, the mean duration of depression 10.6 ± 12.3 years. The most common psychiatric comorbidities in the previous 24 months were anxiety/panic (72.6% and obsessive/compulsive disorders (13.4%, while 35.9% had functional somatic syndromes. Most patients (65.1% reported pain from any cause. Monotherapy with selective serotonin reuptake inhibitors (SSRIs and tricyclic antidepressants (TCAs was prescribed at enrolment in 64.5% and 6.4% of the cases, respectively. The most commonly prescribed agents were sertraline (17.3%, escitalopram (16.2%, venlaflaxine (15.6% and paroxetine (14.8%. The mean HADS subscores for depression and anxiety were 13.3 ± 4.2 and 12.2 ± 3.9, respectively; 76.4% of patients could be defined as being 'probable cases' for depression and 66.2% for anxiety. The

  4. Individuals versus organisms versus populations in the definition of ecological assessment endpoints.

    Science.gov (United States)

    Suter, Glenn W; Norton, Susan B; Fairbrother, Anne

    2005-11-01

    Discussions and applications of the policies and practices of the U.S. Environmental Protection Agency (USEPA) in ecological risk assessment will benefit from continued clarification of the concepts of assessment endpoints and of levels of biological organization. First, assessment endpoint entities and attributes can be defined at different levels of organization. Hence, an organism-level attribute, such as growth or survival, can be applied collectively to a population-level entity such as the brook trout in a stream. Second, assessment endpoints for ecological risk assessment are often mistakenly described as "individual level," which leads to the idea that such assessments are intended to protect individuals. Finally, populations play a more important role in risk assessments than is generally recognized. Organism-level attributes are used primarily for population-level assessments. In addition, the USEPA and other agencies already are basing management decisions on population or community entities and attributes such as production of fisheries, abundance of migratory bird populations, and aquatic community composition.

  5. End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping.

    Science.gov (United States)

    Erden, Mustafa Suphi; Billard, Aude

    2015-06-01

    The goal of this paper is to perform end-point impedance measurements across dominant and nondominant hands while doing airbrush painting and to use the results for developing a robotic assistance scheme. We study airbrush painting because it resembles in many ways manual welding, a standard industrial task. The experiments are performed with the 7 degrees of freedom KUKA lightweight robot arm. The robot is controlled in admittance using a force sensor attached at the end-point, so as to act as a free-mass and be passively guided by the human. For impedance measurements, a set of nine subjects perform 12 repetitions of airbrush painting, drawing a straight-line on a cartoon horizontally placed on a table, while passively moving the airbrush mounted on the robot's end-point. We measure hand impedance during the painting task by generating sudden and brief external forces with the robot. The results show that on average the dominant hand displays larger impedance than the nondominant in the directions perpendicular to the painting line. We find the most significant difference in the damping values in these directions. Based on this observation, we develop a "directional damping" scheme for robotic assistance and conduct a pilot study with 12 subjects to contrast airbrush painting with and without robotic assistance. Results show significant improvement in precision with both dominant and nondominant hands when using robotic assistance.

  6. Minimizing endpoint variability through reinforcement learning during reaching movements involving shoulder, elbow and wrist.

    Science.gov (United States)

    Mehler, David Marc Anton; Reichenbach, Alexandra; Klein, Julius; Diedrichsen, Jörn

    2017-01-01

    Reaching movements are comprised of the coordinated action across multiple joints. The human skeleton is redundant for this task because different joint configurations can lead to the same endpoint in space. How do people learn to use combinations of joints that maximize success in goal-directed motor tasks? To answer this question, we used a 3-degree-of-freedom manipulandum to measure shoulder, elbow and wrist joint movements during reaching in a plane. We tested whether a shift in the relative contribution of the wrist and elbow joints to a reaching movement could be learned by an implicit reinforcement regime. Unknown to the participants, we decreased the task success for certain joint configurations (wrist flexion or extension, respectively) by adding random variability to the endpoint feedback. In return, the opposite wrist postures were rewarded in the two experimental groups (flexion and extension group). We found that the joint configuration slowly shifted towards movements that provided more control over the endpoint and hence higher task success. While the overall learning was significant, only the group that was guided to extend the wrist joint more during the movement showed substantial learning. Importantly, all changes in movement pattern occurred independent of conscious awareness of the experimental manipulation. These findings suggest that the motor system is generally sensitive to its output variability and can optimize joint-space solutions that minimize task-relevant output variability. We discuss biomechanical biases (e.g. joint's range of movement) that could impose hurdles to the learning process.

  7. The application of sulforhodamine B as a colorimetric endpoint in a cytotoxicity assay.

    Science.gov (United States)

    Fricker, S P

    1994-08-01

    Sulforhodamine B (SRB), an aminoxanthene dye, has been used as an assay for total cell protein, initially developed as an endpoint assay for in vitro screening of antitumour agents. In this paper it was investigated as a possible endpoint for a cytotoxicity assay using CHO cells. It is a robust assay with a stable colorimetric endpoint, capable of semi-automation using microtitre equipment. At optimum concentrations (0.05-0.1% SRB) the assay is linear with respect to cell number over a range of 5 x 10(3) to 10(5) cells. In comparative studies with the neutral red assay the SRB assay was more sensitive, and in cytotoxicity assays with test compounds gave comparable dose-response curves. The cytotoxicity of five divalent metal chlorides was assessed using the SRB assay. The order of toxicity was Cd > Hg > Zn > Mn > Mg, that is similar to the expected in vivo ranking. 16 compounds with reported oral LD(50) (rat) ranging from 25,800 mg/kg (glucose) to 1 mg/kg (mercuric chloride) were tested in the assay. The relative toxicities of the compounds in the in vitro SRB assay were similar to the relative in vivo toxicities. The exceptions could be explained by the chemistry of the compounds and could be attributed to pharmacokinetic properties or mechanism of action. This assay can therefore be used to rank chemically similar compounds but is unsuitable as a precise predictor of in vivo toxicity.

  8. Wound Blush Obtainment Is the Most Important Angiographic Endpoint for Wound Healing.

    Science.gov (United States)

    Utsunomiya, Makoto; Takahara, Mitsuyoshi; Iida, Osamu; Yamauchi, Yasutaka; Kawasaki, Daizo; Yokoi, Yoshiaki; Soga, Yoshimistu; Ohura, Norihiko; Nakamura, Masato

    2017-01-23

    This study aimed to assess the optimal angiographic endpoint of endovascular therapy (EVT) for wound healing. Several reports have demonstrated acceptable patency and limb salvage rates following infrapopliteal interventions for the treatment of critical limb ischemia (CLI). However, the optimal angiographic endpoint of EVT remains unclear. We conducted a subanalysis of the prospective multicenter OLIVE (Endovascular Treatment for Infrainguinal Vessels in Patients with Critical Limb Ischemia) registry investigation assessing patients who received infrainguinal EVT for CLI. We analyzed data from 185 limbs with ischemic ulcerations classified as Rutherford class 5 or 6, managed with EVT alone (i.e., not undergoing bypass surgery). The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between final angiographic data and wound healing was assessed employing a Cox proportional hazards model. The overall wound healing rate was 73.5%. The probabilities of wound healing in patients with wound blush obtainment was significantly higher than that of those without wound blush (79.6% vs. 46.5%; p = 0.01). In the multivariate analysis, wound blush obtainment was an independent predictor of wound healing. The presence of wound blush after EVT is significantly associated with wound healing. Wound blush as an angiographic endpoint for EVT may serve as a novel predictor of wound healing in patients with CLI. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Qualitative exploration of HIV-related sexual behaviours and multiple partnerships among Chinese men who have sex with men living in a rural area of Yunnan Province, China.

    Science.gov (United States)

    Chow, Eric P F; Gao, Liangmin; Koo, Fung Kuen; Chen, Liang; Fu, Xiaoxing; Jing, Jun; Wilson, David P; Zhang, Lei

    2013-12-01

    The HIV epidemic has been spreading rapidly among men who have sex with men (MSM) in China. The present study explored the pattern of HIV-related high-risk sexual practices among MSM in a rural Chinese setting. Data were collected by semistructured in-depth interviews conducted among 15 MSM in Yuxi Prefecture, Yunnan Province, China. Fifteen respondents were recruited through a local non-governmental organisation via purposive sampling. Thematic analysis was used. Technological changes, risk behaviours, social stigma and high migration rates have played a significant role in the spread of HIV among MSM in rural China. The Internet has become the primary channel for soliciting casual sex partners in the MSM community. Bisexuality and having concurrent and multiple sexual partners were common among rural MSM. A large number of sexual partners and low condom use in all MSM partnership types were noted. Due to Chinese cultural traditions and social stigma, Chinese rural MSM were reluctant to disclose their homosexuality. Rural-to-urban migrant MSM were often engaged in the commercial sex trade. Rural MSM is a distinctive and complex population with multiple identities in China. Concurrent multiple sexual partnerships, high mobility and low disclosure rate are the major challenges for HIV prevention and intervention programs in MSM.

  10. The influence of having children on HIV-related risk behaviors of female sex workers and their intimate male partners in two Mexico–US border cities

    Science.gov (United States)

    Rolon, Maria Luisa; Syvertsen, Jennifer L.; Robertson, Angela M.; Rangel, M. Gudelia; Martinez, Gustavo; Ulibarri, Monica D.; Servin, Argentina

    2013-01-01

    Among female sex workers who use drugs, the experience of having children and its effect on HIV risk behaviors remains underexplored. We draw from a study of 214 female sex workers and their intimate non-commercial partners in Tijuana and Ciudad Juárez, México (n = 428), approximately 30% of whom have children living with them. During qualitative interviews with 41 of these couples, having children emerged as an important topic. Children influenced partners’ lives and HIV-related risk behaviors in positive and negative ways. Couples perceived that children strengthened their relationships. Concern for children’s well-being motivated couples to contemplate healthier lifestyle changes. However, childrearing costs motivated sex work and structural constraints prevented couples from enacting lifestyle changes. Case studies illustrate these themes and highlight implications for couple- and family-based harm reduction interventions. Specifically, our results suggest a need for economic alternatives to sex work while working with families to develop risk reduction skills. PMID:23418131

  11. HIV-related risk factors among black African migrants and refugees in Christchurch, New Zealand: results from the Mayisha-NZ survey.

    Science.gov (United States)

    Birukila, Gerida; Brunton, Cheryl; Dickson, Nigel

    2013-06-14

    To describe the demographic characteristics of, and HIV-related risk behaviours among, black African migrants and refugees in Christchurch. A cross-sectional survey of black African migrants and refugees in Christchurch was carried out. Ten trained African community researchers recruited study participants in social venues and events frequented by Africans. A short self-completed questionnaire collected data on demographic characteristics, previous HIV testing, HIV risk perception, previous STI diagnosis, utilization of health services and sexual behaviours. Valid questionnaires were obtained from 245 respondents (150 men and 95 women) with a mean age of 28 years (range 16 to 58). Participants came from 13 different African countries. Risk factors for HIV identified in this study included: low condom use, low HIV risk perception, having more than one sexual partner, previous STI diagnosis and lack of voluntary testing for HIV. Our findings justify the need for developing an HIV prevention strategy for black Africans in New Zealand that is informed by local evidence. This strategy should also address sexual health needs of Africans including barriers to condom use, the availability of HIV/STI screening services and targeting sexual behaviours that increase vulnerability to HIV infection.

  12. HIV-related stigma, social norms, and HIV testing in Soweto and Vulindlela, South Africa: National Institutes of Mental Health Project Accept (HPTN 043).

    Science.gov (United States)

    Young, Sean D; Hlavka, Zdenek; Modiba, Precious; Gray, Glenda; Van Rooyen, Heidi; Richter, Linda; Szekeres, Greg; Coates, Thomas

    2010-12-15

    HIV testing is necessary to curb the increasing epidemic. However, HIV-related stigma and perceptions of low likelihood of societal HIV testing may reduce testing rates. This study aimed to explore this association in South Africa, where HIV rates are extraordinarily high. Data were taken from the Soweto and Vulindlela, South African sites of Project Accept, a multinational HIV prevention trial. Self-reported HIV testing, stigma, and social norms items were used to study the relationship between HIV testing, stigma, and perceptions about societal testing rates. The stigma items were broken into 3 factors: negative attitudes, negative perceptions about people living with HIV, and perceptions of fair treatment for people living with HIV (equity). Results from a univariate logistic regression suggest that history of HIV testing was associated with decreased negative attitudes about people living with HIV/AIDS, increased perceptions that people living with HIV/AIDS experience discrimination, and increased perceptions that people with HIV should be treated equitably. Results from a multivariate logistic regression confirm these effects and suggest that these differences vary according to sex and age. Compared with people who had never tested for HIV, those who had previously tested were more likely to believe that the majority of people have tested for HIV. Data suggest that interventions designed to increase HIV testing in South Africa should address stigma and perceptions of societal testing.

  13. “Inside These Fences is Our Own Little World”: Prison-Based HIV Testing and HIV-Related Stigma Among Incarcerated Men and Women

    Science.gov (United States)

    Muessig, Kathryn E.; Rosen, David L.; Farel, Claire E.; White, Becky L.; Filene, Eliza J.; Wohl, David A.

    2016-01-01

    Correctional facilities offer opportunities to provide comprehensive HIV services including education, testing, treatment, and coordination of post-release care. However, these services may be undermined by unaddressed HIV stigma. As part of a prison-based HIV testing study, we interviewed 76 incarcerated men and women from the North Carolina State prison system. The sample was 72% men, median age 31.5 years (range: 19 to 60). Thematic analysis revealed high levels of HIV-related fear and stigma, homophobia, incomplete HIV transmission knowledge, beliefs that HIV is highly contagious within prisons (“HIV miasma”), and the view of HIV testing as protective. Interviewees described social distancing behaviors and coping mechanisms they perceived to be protective, including knowing their HIV status and avoiding contact with others and shared objects. Interviewees endorsed universal testing, public HIV status disclosure, and segregation of HIV-positive inmates. Intensified education and counseling efforts are needed to ameliorate entrenched HIV-transmission fears and stigmatizing beliefs. PMID:27459162

  14. HIV-related stigma, racial discrimination, and gender discrimination: Pathways to physical and mental health-related quality of life among a national cohort of women living with HIV.

    Science.gov (United States)

    Logie, Carmen H; Wang, Ying; Lacombe-Duncan, Ashley; Wagner, Anne C; Kaida, Angela; Conway, Tracey; Webster, Kath; de Pokomandy, Alexandra; Loutfy, Mona R

    2018-02-01

    Social inequities compromise health-related quality of life (HR-QoL) among women living with HIV (WLWH). Little is known about health impacts of intersecting stigma based on HIV status, race and gender among WLWH or potential mechanisms to promote HR-QoL. We tested pathways from multiple types of stigma (HIV-related, racial, gender) to physical and mental HR-QoL utilizing baseline survey data from a national cohort of WLWH in Canada (2013-2015). Structural equation modeling was conducted using maximum likelihood estimation methods to test the direct effects of HIV-related stigma, racial discrimination, and gender discrimination on HR-QoL and indirect effects via social support and economic insecurity, adjusting for socio-demographic factors. Among 1425 WLWH (median age: 43years [IQR=35-50]), HIV-related stigma and gender discrimination had significant direct effects on mental HR-QoL. Social support mediated the relationship between HIV-related stigma and mental HR-QoL, accounting for 22.7% of the effect. Social support accounted for 41.4% of the effect of gender discrimination on mental HR-QoL. Economic insecurity accounted for 14.3% of the effect of HIV-related stigma, and 42.4% of the effect of racial discrimination, on physical HR-QoL. Fit indices suggest good model fit (χ 2 [1]=3.319, p=0.069; CFI=0.998; RMSEA=0.042 (90% CI: 0-0.069); SRMR=0.004). Findings reveal complex relationships between intersecting stigma and HR-QoL. Strategies that address intersecting stigma and economic insecurity among WLWH may prevent the harmful impacts of HIV-related stigma and gender discrimination on physical HR-QoL. Increasing social support may mitigate the impacts of stigma on mental health. Findings can inform multi-level interventions to promote health and wellbeing among WLWH. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A comparison of the clinical features of depression in HIV-positive ...

    African Journals Online (AJOL)

    AIDS with prevalence 2 to 3 times higher than the general population. It's still questionable whether HIV related depression is clinically different from depression in HIV-negative populations, a fact that could have treatment implications.This study ...

  16. Saccadic adaptation in visually normal individuals using saccadic endpoint variability from amblyopia.

    Science.gov (United States)

    Raashid, Rana Arham; Wong, Agnes M F; Blakeman, Alan; Goltz, Herbert C

    2015-01-15

    Saccadic adaptation is affected by the spatial variability of the adapting error signal. Recently, we have shown that saccadic adaptation is reduced in anisometropic amblyopia, possibly impacted by spatially imprecise saccades. Here, we tested this idea by quantifying the saccadic endpoint variability difference between people with anisometropic amblyopia and visually normal individuals. We then applied this difference to the second target step distribution during saccadic adaptation in visually normal people to test whether their performance diminished to a similar extent as participants with amblyopia. Ten visually normal adults performed a double-step adaptation task (±19°, followed by 4° back-steps) with the nondominant eye under two conditions: "consistent error," using a constant back-step; and "variable error," using a variable (σdiff) back-step determined by subtracting the saccadic endpoint variability in controls from that in anisometropic amblyopia during amblyopic/nondominant eye viewing. Percentage change in saccadic gains, percentage retention, and adaptation time constants were analyzed. Percentage change in saccadic gains decreased significantly during the variable error condition (50% ± 10%) compared to the consistent error condition (69% ± 9%; P = 0.0008). Percentage retention and time constants did not differ between conditions. The adaptation magnitude during the variable error condition was comparable to the previous percentage adaptation in people with anisometropic amblyopia during the consistent error condition with amblyopic eye viewing. Our findings indicate that adding exogenous spatial noise to the adapting step consistent with the saccadic endpoint variability difference between amblyopic and visually normal groups is sufficient to reduce saccadic adaptation in healthy individuals. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  17. The impact of SASA!, a community mobilization intervention, on reported HIV-related risk behaviours and relationship dynamics in Kampala, Uganda

    Directory of Open Access Journals (Sweden)

    Nambusi Kyegombe

    2014-11-01

    Full Text Available Introduction: Intimate partner violence (IPV violates women's human rights, and it is a serious public health concern associated with increased HIV risk. SASA!, a phased community mobilization intervention, engages communities to prevent IPV and promote gender equity. The SASA! study assessed the community-level impact of SASA! on reported HIV-related risk behaviours and relationship dynamics. Methods: Data were collected as part of a cluster randomized controlled trial conducted between 2007 and 2012 in eight communities in Kampala. An adjusted cluster-level intention to treat analysis, compares secondary outcomes in intervention and control communities at follow-up. The qualitative evaluation explored participants’ subjective experience of SASA!. A total of 82 in-depth interviews were audio recorded at follow-up, transcribed verbatim and analyzed using thematic analysis. Results: Men in intervention communities were significantly more likely than controls to report a broad range of HIV-protective behaviours, including higher levels of condom use (aRR 2.03, 95% CI 1.22–3.39, HIV testing (aRR 1.50, 95% CI 1.13–2.00 and fewer concurrent partners (aRR 0.60, 95% CI 0.37–0.97. They were also more likely to report increased joint decision-making (aRR 1.92, 95% CI 1.27–2.91, greater male participation in household tasks (aRR 1.48, 95% CI 1.09–2.01, more open communication and greater appreciation of their partner's work inside (aRR 1.31, 95% CI 1.04–1.66 and outside (aRR 1.49, 95% CI 1.08–2.06 the home. For women, all outcomes were in the hypothesized direction, but effect sizes were smaller. Only some achieved statistical significance. Women in intervention communities were significantly more likely to report being able to refuse sex with their partners (aRR 1.16, 95% CI 1.00–1.35, joint decision-making (aRR 1.37, 95% CI 1.06–1.78 and more open communication on a number of indicators. Qualitative interviews suggest that shifts

  18. Survival variability of controls and definition of imaging endpoints for longitudinal follow-up of pancreatic ductal adenocarcinoma in rats.

    Science.gov (United States)

    Akladios, Cherif; Ignat, Mihaela; Mutter, Didier; Aprahamian, Marc

    2017-01-01

    The 3Rs guideline is the gold standard for ethics in animal experimentation. Two of those rules, namely refinement and reduction, require further improvement. The objective of this study was to define pathways to better compliance with these prerequisites. Two methods which move us in this direction are: (1) using small animal imaging techniques for pancreatic ductal adenocarcinoma (PDAC) follow-up and (2) reduction of the number of control animals included in a study of PDAC progression under treatment. Firstly, we used MicroCT scan to diagnose events showing PDAC progression prior to any clinical symptoms to thereby define more humane endpoints identifiable before any painful phenomenon is observed. Secondly, in order to test the hypothesis of using a reference control group in all preclinical studies of a new treatment of PDAC, we investigated the stability of the results obtained with the control groups in three successive identical studies comparing placebo and gemcitabine in tumor-bearing Lewis rats. Two imaging endpoints were found. The first was the observation of a liver metastasis assessing PDAC diffusion and, earlier than liver metastasis, the presence of bands of fluid along the flanks, with more or less a medial displacement of bowel and solid viscera, reflecting a peritoneal ascites. Results of the longitudinal follow-up of rats in the gemcitabine study revealed heterogeneity in the survival rate in the three control groups, as opposed to the survival rate in the three treated groups which did not differ statistically. As a result, the significance of improved survival with chemotherapy varied greatly according to the control group used for the comparison, ranging from no impact to a highly significant effect. The early detection by the means of animal imaging of one or more signs indicating the onset of a critical step in the development of the disease (e.g., ascites or/and metastasis) allows the researcher to prevent the occurrence of animal pain

  19. Comparison of audio computer assisted self-interview and face-to-face interview methods in eliciting HIV-related risks among men who have sex with men and men who inject drugs in Nigeria.

    Science.gov (United States)

    Adebajo, Sylvia; Obianwu, Otibho; Eluwa, George; Vu, Lung; Oginni, Ayo; Tun, Waimar; Sheehy, Meredith; Ahonsi, Babatunde; Bashorun, Adebobola; Idogho, Omokhudu; Karlyn, Andrew

    2014-01-01

    Face-to-face (FTF) interviews are the most frequently used means of obtaining information on sexual and drug injecting behaviours from men who have sex with men (MSM) and men who inject drugs (MWID). However, accurate information on these behaviours may be difficult to elicit because of sociocultural hostility towards these populations and the criminalization associated with these behaviours. Audio computer assisted self-interview (ACASI) is an interviewing technique that may mitigate social desirability bias in this context. This study evaluated differences in the reporting of HIV-related risky behaviours by MSM and MWID using ACASI and FTF interviews. Between August and September 2010, 712 MSM and 328 MWID in Nigeria were randomized to either ACASI or FTF interview for completion of a behavioural survey that included questions on sensitive sexual and injecting risk behaviours. Data were analyzed separately for MSM and MWID. Logistic regression was run for each behaviour as a dependent variable to determine differences in reporting methods. MSM interviewed via ACASI reported significantly higher risky behaviours with both women (multiple female sexual partners 51% vs. 43%, p = 0.04; had unprotected anal sex with women 72% vs. 57%, p = 0.05) and men (multiple male sex partners 70% vs. 54%, p≤0.001) than through FTF. Additionally, they were more likely to self-identify as homosexual (AOR: 3.3, 95%CI:2.4-4.6) and report drug use in the past 12 months (AOR:40.0, 95%CI: 9.6-166.0). MWID interviewed with ACASI were more likely to report needle sharing (AOR:3.3, 95%CI:1.2-8.9) and re-use (AOR:2.2, 95%CI:1.2-3.9) in the past month and prior HIV testing (AOR:1.6, 95%CI 1.02-2.5). The feasibility of using ACASI in studies and clinics targeting key populations in Nigeria must be explored to increase the likelihood of obtaining more accurate data on high risk behaviours to inform improved risk reduction strategies that reduce HIV transmission.

  20. Comparison of audio computer assisted self-interview and face-to-face interview methods in eliciting HIV-related risks among men who have sex with men and men who inject drugs in Nigeria.

    Directory of Open Access Journals (Sweden)

    Sylvia Adebajo

    Full Text Available INTRODUCTION: Face-to-face (FTF interviews are the most frequently used means of obtaining information on sexual and drug injecting behaviours from men who have sex with men (MSM and men who inject drugs (MWID. However, accurate information on these behaviours may be difficult to elicit because of sociocultural hostility towards these populations and the criminalization associated with these behaviours. Audio computer assisted self-interview (ACASI is an interviewing technique that may mitigate social desirability bias in this context. METHODS: This study evaluated differences in the reporting of HIV-related risky behaviours by MSM and MWID using ACASI and FTF interviews. Between August and September 2010, 712 MSM and 328 MWID in Nigeria were randomized to either ACASI or FTF interview for completion of a behavioural survey that included questions on sensitive sexual and injecting risk behaviours. Data were analyzed separately for MSM and MWID. Logistic regression was run for each behaviour as a dependent variable to determine differences in reporting methods. RESULTS: MSM interviewed via ACASI reported significantly higher risky behaviours with both women (multiple female sexual partners 51% vs. 43%, p = 0.04; had unprotected anal sex with women 72% vs. 57%, p = 0.05 and men (multiple male sex partners 70% vs. 54%, p≤0.001 than through FTF. Additionally, they were more likely to self-identify as homosexual (AOR: 3.3, 95%CI:2.4-4.6 and report drug use in the past 12 months (AOR:40.0, 95%CI: 9.6-166.0. MWID interviewed with ACASI were more likely to report needle sharing (AOR:3.3, 95%CI:1.2-8.9 and re-use (AOR:2.2, 95%CI:1.2-3.9 in the past month and prior HIV testing (AOR:1.6, 95%CI 1.02-2.5. CONCLUSION: The feasibility of using ACASI in studies and clinics targeting key populations in Nigeria must be explored to increase the likelihood of obtaining more accurate data on high risk behaviours to inform improved risk reduction strategies

  1. Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression.

    Science.gov (United States)

    Turan, Bulent; Smith, Whitney; Cohen, Mardge H; Wilson, Tracey E; Adimora, Adaora A; Merenstein, Daniel; Adedimeji, Adebola; Wentz, Eryka L; Foster, Antonina G; Metsch, Lisa; Tien, Phyllis C; Weiser, Sheri D; Turan, Janet M

    2016-06-01

    Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence. The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced. The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence. Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.

  2. Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

    Science.gov (United States)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

    2013-01-01

    Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

  3. Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.

    Science.gov (United States)

    Boyer, Cherrie B; Greenberg, Lauren; Chutuape, Kate; Walker, Bendu; Monte, Dina; Kirk, Jennifer; Ellen, Jonathan M

    2017-02-01

    The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p development of effective evidence-based prevention strategies.

  4. A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.

    Science.gov (United States)

    Junglen, Angela G; Smith, Brian C; Coleman, Jennifer A; Pacella, Maria L; Boarts, Jessica M; Jones, Tracy; Feeny, Norah C; Ciesla, Jeffrey A; Delahanty, Douglas L

    2017-11-01

    People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.

  5. Mesoscale simulation of semiflexible chains. I. Endpoint distribution and chain dynamics

    Science.gov (United States)

    Groot, Robert D.

    2013-06-01

    The endpoint distribution and dynamics of semiflexible fibers are studied by numerical simulation. A brief overview is given over the analytical theory of flexible and semiflexible polymers. In particular, a closed expression is given for the relaxation spectrum of wormlike chains, which determines polymer diffusion and rheology. Next a simulation model for wormlike chains with full hydrodynamic interaction is described, and relations for the bending and torsion modulus are given. Two methods are introduced to include torsion stiffness into the model. The model is validated by simulating single chains in a heat bath, and comparing the endpoint distribution of the chains with established Monte Carlo results. It is concluded that torsion stiffness leads to a slightly shorter effective persistence length for a given bending stiffness. To further validate the simulation model, polymer diffusion is studied for fixed persistence length and varying polymer length N. The diffusion constant shows crossover from Rouse (D ∝ N-1) to reptation behaviour (D ∝ N-2). The terminal relaxation time obtained from the monomer displacement is consistent with the theory of wormlike chains. The probability for chain crossing has also been studied. This probability is so low that it does not influence the present results.

  6. Old model organisms and new behavioral end-points: Swimming alteration as an ecotoxicological response.

    Science.gov (United States)

    Faimali, Marco; Gambardella, Chiara; Costa, Elisa; Piazza, Veronica; Morgana, Silvia; Estévez-Calvar, Noelia; Garaventa, Francesca

    2017-07-01

    Behavioral responses of aquatic organisms have received much less attention than developmental or reproductive ones due to the scarce presence of user-friendly tools for their acquisition. The technological development of data acquisition systems for quantifying behavior in the aquatic environment and the increase of studies on the understanding the relationship between the behavior of aquatic organisms and the physiological/ecological activities have generated renewed interest in using behavioral responses also in marine ecotoxicology. Recent reviews on freshwater environment show that behavioral end-points are comparatively fast and sensitive, and warrant further attention as tools for assessing the toxicological effects of environmental contaminants. In this mini-review, we perform a systematic analysis of the most recent works that have used marine invertebrate swimming alteration as behavioral end-point in ecotoxicological studies by assessing the differences between behavioral and acute responses in a wide range of species, in order to compare their sensitivity. Copyright © 2016. Published by Elsevier Ltd.

  7. Evaluation and QSAR modeling on multiple endpoints of estrogen activity based on different bioassays.

    Science.gov (United States)

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2008-02-01

    There is a great need for an effective means of rapidly assessing endocrine-disrupting activity, especially estrogen-simulating activity, due to the large number of chemicals that have serious adverse effects on the environment. Many approaches using a variety of biological screening assays are used to identify endocrine disrupting chemicals. The present investigation analyzes the consistency and peculiarity of information from different experimental assays collected from a literature survey, by studying the correlation of the different endpoints. In addition, the activity values of more widely used selected bioassays have been combined by principle components analysis (PCA) to build one cumulative endpoint, the estrogen activity index (EAI), for priority setting to identify chemicals most likely possessing estrogen activity for early entry into screening. This index was then modeled using only a few theoretical molecular descriptors. The constructed MLR-QSAR model has been statistically validated for its predictive power, and can be proposed as a preliminary evaluative method to screen/prioritize estrogens according to their integrated estrogen activity, just starting from molecular structure.

  8. Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

    DEFF Research Database (Denmark)

    Dellavalle, B; Kirchhoff, J; Maretty, L

    2014-01-01

    anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...... versus infrared thermometry: cervical dislocation: Pearson R = 0·99, R 2 = 0·98, slope = 1·01, y-intercept = 0·55; ECM: 0·99, 0·98, 1·06, -2·4; and SMA: 0·98, 0·97, 1·14, -5·6. Implementation of the 30 °C endpoint captured all lethal infections. However, some animals with BT below 30 °C were not deemed...

  9. Transgenerational endpoints provide increased sensitivity and insight into multigenerational responses of Lymnaea stagnalis exposed to cadmium.

    Science.gov (United States)

    Reátegui-Zirena, Evelyn G; Fidder, Bridgette N; Olson, Adric D; Dawson, Daniel E; Bilbo, Thomas R; Salice, Christopher J

    2017-05-01

    Ecotoxicology provides data to inform environmental management. Many testing protocols do not consider offspring fitness and toxicant sensitivity. Cadmium (Cd) is a well-studied and ubiquitous toxicant but little is known about the effects on offspring of exposed parents (transgenerational effects). This study had three objectives: to identify endpoints related to offspring performance; to determine whether parental effects would manifest as a change in Cd tolerance in offspring and how parental exposure duration influenced the manifestation of parental effects. Adult snails were exposed to Cd 0, 25, 50, 100, 200 and 400 μg Cd/L for eight weeks. There were effects on adult endpoints (e.g., growth, reproduction) but only at the highest concentrations (>100 μg/L). Alternatively, we observed significant transgenerational effects at all Cd concentrations. Surprisingly, we found increased Cd tolerance in hatchlings from all parental Cd exposure concentrations even though eggs and hatchlings were in Cd-free conditions for 6 weeks. Explicit consideration of offspring performance adds value to current toxicity testing protocols. Parental exposure duration has important implications for offspring effects and that contaminant concentrations that are not directly toxic to parents can cause transgenerational changes in resistance that have significant implications for toxicity testing and adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Fixed-dose Sumatriptan/Naproxen Sodium Compared with each Monotherapy Utilizing the Novel Composite Endpoint of Sustained Pain-free/no Adverse Events.

    Science.gov (United States)

    Landy, Stephen; White, Jonathan; Lener, Shelly E; McDonald, Susan A

    2009-05-01

    A novel composite endpoint, sustained pain-free/no adverse events, was recently proposed as a more rigorous means of capturing in a single measure the attributes of migraine pharmacotherapy that patients consider most important: rapid and sustained pain-free response with no side-effects. Using pooled data from two replicate randomized, double-blind, parallel-group, placebo-controlled studies, this post hoc analysis compared the fixed-dose combination tablet sumatriptan/naproxen sodium (n = 726) with sumatriptan monotherapy (n = 723), naproxen sodium monotherapy (n = 720), and placebo (n = 742) with respect to sustained pain-free/no adverse events and closely related composite measures. Sustained pain-free/no adverse events was defined as having both a sustained pain-free response from 2 through 24 hours post-dose with no use of rescue medication and having no adverse events within up to 5 days after dosing with study medication. The percentage of patients with sustained pain-free/no adverse events was 16% with sumatriptan/naproxen sodium compared with 11%, 9% and 7% for sumatriptan, naproxen sodium and placebo, respectively (ppain-free/no adverse events within 1 day; (2) sustained pain-free/no drug-related adverse events within up to 5 days; (3) sustained pain-free/no drug-related adverse events within 1 day; (4) sustained pain relief/no adverse events within up to 5 days; and (5) sustained pain relief/no adverse events within 1 day. The results demonstrate the superiority of sumatriptan/naproxen sodium to sumatriptan monotherapy, naproxen sodium monotherapy and placebo with respect to the rigorous and clinically relevant endpoint of sustained pain-free/no adverse events and reinforce the usefulness of utilizing this new composite endpoint.

  11. Automatic Identification of the Repolarization Endpoint by Computing the Dominant T-wave on a Reduced Number of Leads.

    Science.gov (United States)

    Giuliani, C; Agostinelli, A; Di Nardo, F; Fioretti, S; Burattini, L

    2016-01-01

    Electrocardiographic (ECG) T-wave endpoint (Tend) identification suffers lack of reliability due to the presence of noise and variability among leads. Tend identification can be improved by using global repolarization waveforms obtained by combining several leads. The dominant T-wave (DTW) is a global repolarization waveform that proved to improve Tend identification when computed using the 15 (I to III, aVr, aVl, aVf, V1 to V6, X, Y, Z) leads usually available in clinics, of which only 8 (I, II, V1 to V6) are independent. The aim of the present study was to evaluate if the 8 independent leads are sufficient to obtain a DTW which allows a reliable Tend identification. To this aim Tend measures automatically identified from 15-dependent-lead DTWs of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were compared with those obtained from 8-independent-lead DTWs. Results indicate that Tend distributions have not statistically different median values (CHS: 340 ms vs. 340 ms, respectively; AMIP: 325 ms vs. 320 ms, respectively), besides being strongly correlated (CHS: ρ=0.97, AMIP: 0.88; Plead DTWs is statistically equivalent to measuring Tend from the 8-independent-lead DTWs. In conclusion, for the clinical purpose of automatic Tend identification from DTW, the 8 independent leads can be used without a statistically significant loss of accuracy but with a significant decrement of computational effort. The lead dependence of 7 out of 15 leads does not introduce a significant bias in the Tend determination from 15 dependent lead DTWs.

  12. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays.

    Directory of Open Access Journals (Sweden)

    Jason M Wilham

    2010-12-01

    Full Text Available A major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. Such measurements have typically required prolonged bioassays in animals. Highly sensitive, but generally non-quantitative, prion detection methods have been developed based on prions' ability to seed the conversion of normally soluble protease-sensitive forms of prion protein to protease-resistant and/or amyloid fibrillar forms. Here we describe an approach for estimating the relative amount of prions using a new prion seeding assay called real-time quaking induced conversion assay (RT-QuIC. The underlying reaction blends aspects of the previously described quaking-induced conversion (QuIC and amyloid seeding assay (ASA methods and involves prion-seeded conversion of the alpha helix-rich form of bacterially expressed recombinant PrP(C to a beta sheet-rich amyloid fibrillar form. The RT-QuIC is as sensitive as the animal bioassay, but can be accomplished in 2 days or less. Analogous to end-point dilution animal bioassays, this approach involves testing of serial dilutions of samples and statistically estimating the seeding dose (SD giving positive responses in 50% of replicate reactions (SD(50. Brain tissue from 263K scrapie-affected hamsters gave SD(50 values of 10(11-10(12/g, making the RT-QuIC similar in sensitivity to end-point dilution bioassays. Analysis of bioassay-positive nasal lavages from hamsters affected with transmissible mink encephalopathy gave SD(50 values of 10(3.5-10(5.7/ml, showing that nasal cavities release substantial prion infectivity that can be rapidly detected. Cerebral spinal fluid from 263K scrapie-affected hamsters contained prion SD(50 values of 10(2.0-10(2.9/ml. RT-QuIC assay also discriminated deer chronic wasting disease and sheep scrapie brain samples from normal control samples. In principle, end-point dilution quantitation can be applied to many types of

  13. Towards better environmental performance of wastewater sludge treatment using endpoint approach in LCA methodology

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    Isam Alyaseri

    2017-03-01

    Full Text Available The aim of this study is to use the life cycle assessment method to measure the environmental performance of the sludge incineration process in a wastewater treatment plant and to propose an alternative that can reduce the environmental impact. To show the damages caused by the treatment processes, the study aimed to use an endpoint approach in evaluating impacts on human health, ecosystem quality, and resources due to the processes. A case study was taken at Bissell Point Wastewater Treatment Plant in Saint Louis, Missouri, U.S. The plant-specific data along with literature data from technical publications were used to build an inventory, and then analyzed the environmental burdens from sludge handling unit in the year 2011. The impact assessment method chosen was ReCipe 2008. The existing scenario (dewatering-multiple hearth incineration-ash to landfill was evaluated and three alternative scenarios (fluid bed incineration and anaerobic digestion with and without land application with energy recovery from heat or biogas were proposed and analyzed to find the one with the least environmental impact. The existing scenario shows that the most significant impacts are related to depletion in resources and damage to human health. These impacts mainly came from the operation phase (electricity and fuel consumption and emissions related to combustion. Alternatives showed better performance than the existing scenario. Using ReCipe endpoint methodology, and among the three alternatives tested, the anaerobic digestion had the best overall environmental performance. It is recommended to convert to fluid bed incineration if the concerns were more about human health or to anaerobic digestion if the concerns were more about depletion in resources. The endpoint approach may simplify the outcomes of this study as follows: if the plant is converted to fluid bed incineration, it could prevent an average of 43.2 DALYs in human life, save 0.059 species in the area

  14. Blend uniformity end-point determination using near-infrared spectroscopy and multivariate calibration.

    Science.gov (United States)

    Sulub, Yusuf; Konigsberger, Michele; Cheney, James

    2011-06-01

    A multivariate calibration approach using near-infrared (NIR) spectroscopy for determining blend uniformity end-point of a pharmaceutical solid dosage form containing 29.4% (w/w) drug load with three major excipients (crospovidone, lactose, and microcrystalline cellulose) is presented. A set of 21 off-line, static calibration samples were used to develop a multivariate partial least-squares (PLS) calibration model for on-line predictions of the API content during the blending process. The concentrations of the API and the three major excipients were varied randomly to minimize correlations between the components. A micro-electrical-mechanical-system (MEMS) based NIR spectrometer was used for this study. To minimize spectral differences between the static and dynamic measurement modes, the acquired NIR spectra were preprocessed using standard normal variate (SNV) followed by second derivative Savitsky-Golay using 21 points. The performance of the off-line PLS calibration model were evaluated in real-time on 67 production scale (750L bin size) blend experiments conducted over 3 years. The real-time API-NIR (%) predictions of all batches ranged from 93.7% to 104.8% with standard deviation ranging from 0.5% to 1.8%. These results showed the attainment of blend homogeneity and were confirmed with content uniformity by HPLC of respective manufactured tablets values ranging from 95.4% to 101.3% with standard deviation ranging from 0.5% to 2.1%. Furthermore, the performance of the PLS calibration model was evaluated against off-target batches manufactured with high and low amounts of water during the granulation phase of production. This approach affects the particle size and hence blending. All the off-target batches exhibited API-NIR (%) predictions of 94.6% to 103.5% with standard deviation ranging from 0.7% to 1.9%. Using off-target data, a systematic approach was developed to determine blend uniformity end-point. This was confirmed with 3 production scale batches

  15. Towards better environmental performance of wastewater sludge treatment using endpoint approach in LCA methodology.

    Science.gov (United States)

    Alyaseri, Isam; Zhou, Jianpeng

    2017-03-01

    The aim of this study is to use the life cycle assessment method to measure the environmental performance of the sludge incineration process in a wastewater treatment plant and to propose an alternative that can reduce the environmental impact. To show the damages caused by the treatment processes, the study aimed to use an endpoint approach in evaluating impacts on human health, ecosystem quality, and resources due to the processes. A case study was taken at Bissell Point Wastewater Treatment Plant in Saint Louis, Missouri, U.S. The plant-specific data along with literature data from technical publications were used to build an inventory, and then analyzed the environmental burdens from sludge handling unit in the year 2011. The impact assessment method chosen was ReCipe 2008. The existing scenario (dewatering-multiple hearth incineration-ash to landfill) was evaluated and three alternative scenarios (fluid bed incineration and anaerobic digestion with and without land application) with energy recovery from heat or biogas were proposed and analyzed to find the one with the least environmental impact. The existing scenario shows that the most significant impacts are related to depletion in resources and damage to human health. These impacts mainly came from the operation phase (electricity and fuel consumption and emissions related to combustion). Alternatives showed better performance than the existing scenario. Using ReCipe endpoint methodology, and among the three alternatives tested, the anaerobic digestion had the best overall environmental performance. It is recommended to convert to fluid bed incineration if the concerns were more about human health or to anaerobic digestion if the concerns were more about depletion in resources. The endpoint approach may simplify the outcomes of this study as follows: if the plant is converted to fluid bed incineration, it could prevent an average of 43.2 DALYs in human life, save 0.059 species in the area from extinction

  16. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib

    Science.gov (United States)

    Yeo, Astrid; Warren, Liling; Aponte, Jennifer; Johansson, Kelley; Barnes, Allison; MacPhee, Colin; Davies, Richard; Chissoe, Stephanie; O’Donoghue, Michelle L.; White, Harvey D.

    2017-01-01

    Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants) using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction) as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1) and identified three novel loci (TOMM5, FRMD5 and LPL) using the GWAS-significance threshold P≤5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2) within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores) and one common locus (minor allele frequency 0.24) with genotype by treatment interaction effect passing the GWAS

  17. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

    Directory of Open Access Journals (Sweden)

    Astrid Yeo

    Full Text Available Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY and one in acute coronary syndrome (SOLID-TIMI 52. No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%. We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1 and identified three novel loci (TOMM5, FRMD5 and LPL using the GWAS-significance threshold P≤5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2 within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores and one common locus (minor allele frequency 0.24 with genotype by treatment interaction effect passing the GWAS

  18. Trust, confidentiality, and the acceptability of sharing HIV-related patient data: lessons learned from a mixed methods study about Health Information Exchanges.

    Science.gov (United States)

    Maiorana, Andre; Steward, Wayne T; Koester, Kimberly A; Pearson, Charles; Shade, Starley B; Chakravarty, Deepalika; Myers, Janet J

    2012-04-19

    Concerns about the confidentiality of personal health information have been identified as a potential obstacle to implementation of Health Information Exchanges (HIEs). Considering the stigma and confidentiality issues historically associated with human immunodeficiency virus (HIV) disease, we examine how trust-in technology, processes, and people-influenced the acceptability of data sharing among stakeholders prior to implementation of six HIEs intended to improve HIV care in parts of the United States. Our analyses identify the kinds of concerns expressed by stakeholders about electronic data sharing and focus on the factors that ultimately facilitated acceptability of the new exchanges. We conducted 549 surveys with patients and 66 semi-structured interviews with providers and other stakeholders prior to implementation of the HIEs to assess concerns about confidentiality in the electronic sharing of patient data. The patient quantitative data were analyzed using SAS 9.2 to yield sample descriptive statistics. The analysis of the qualitative interviews with providers and other stakeholders followed an open-coding process, and convergent and divergent perspectives emerging from those data were examined within and across the HIEs. We found widespread acceptability for electronic sharing of HIV-related patient data through HIEs. This acceptability appeared to be driven by growing comfort with information technologies, confidence in the security protocols utilized to protect data, trust in the providers and institutions who use the technologies, belief in the benefits to the patients, and awareness that electronic exchange represents an enhancement of data sharing already taking place by other means. HIE acceptability depended both on preexisting trust among patients, providers, and institutions and on building consensus and trust in the HIEs as part of preparation for implementation. The process of HIE development also resulted in forging shared vision among

  19. A survey on HIV-related health-seeking behaviors among transgender individuals in Jakarta, based on the theory of planned behavior.

    Science.gov (United States)

    Prabawanti, Ciptasari; Dijkstra, Arie; Riono, Pandu; Hartana, Gagan

    2015-11-16

    Male-to-female transgender (waria) individuals are at high risk for HIV. This study aims at mapping the psychological determinants of four HIV-related health-seeking behaviors. This knowledge can be used to develop effective interventions to prevent the spread of HIV/AIDS. The study involved 209 waria from five districts in Jakarta, selected with a cluster sampling procedure. Cross-sectional data were gathered through structured interviews. The four examined behaviors are, visiting sexually transmitted infections (STIs) services regularly, adherence to STI treatment, taking an HIV test and picking up the result of HIV test. For all four behaviors, specific measures of the psychological determinants as defined by the Theory of Planned Behavior were developed: attitudes, subjective norms and perceived behavioral control (PBC). Logistic regression analyses were conducted with these three psychological measures as independent variables and the behaviors as dependent variables. Of the 209 waria, 20.6 % had never visited STI services in the last 6 months, while 56.5 % had visited the services once or twice, and 23 % had visited the service three or more times. A HIV test had been taken by 90.4 % of the waria, and of those, 64.6 % had picked up the results. About 85 % of the waria who did a HIV test had been tested for HIV one or two times in the last 6 months and 10 % had been tested three to four times. The variance in behaviors that was explained by the concepts defined in the Theory of Planned Behavior ranged from 15 to 70 %; PBC was the most powerful predictor. Furthermore, the results showed that in several cases the relationships of attitudes or subjective norms with the dependent variable were mediated by one or both other independent variables. The results regarding the prominent role of PBC suggest that interventions should increase waria's control over the behavior: Engaging in specific desired behaviors should be made easier for them. Besides, waria

  20. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data.

    Science.gov (United States)

    Paula, Adelzon A; Schechter, Mauro; Tuboi, Suely H; Faulhaber, José Claudio; Luz, Paula M; Veloso, Valdiléa G; Moreira, Ronaldo I; Grinsztejn, Beatriz; Harrison, Lee H; Pacheco, Antonio G

    2014-01-01

    After antiretroviral therapy (ART) became available, there was a decline in the number of deaths in persons infected with HIV. Thereafter, there was a decrease in the proportion of deaths attributed to opportunistic infections and an increase in the proportion of deaths attributed to chronic comorbidities. Herein we extend previous observations from a nationwide survey on temporal trends in causes of death in HIV-infected patients in Brazil. We describe temporal trends in causes of death among adults who had HIV/AIDS listed in the death certificate to those who did not. All death certificates issued in Brazil from 1999 to 2011 and listed in the national mortality database were included. Generalized linear mixed-effects logistic models were used to study temporal trends in proportions. In the HIV-infected population, there was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer, external causes, cardiovascular diseases (CVD) and diabetes mellitus (DM), respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For tuberculosis (TB), there was an adjusted average increase of 0.3%/year and a decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared to 1999, the odds ratio (OR) for cancer, external causes, CVD, DM, or TB in the HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non-HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67. Interactions between year as a continuous or categorical variable and HIV were significant (pHIV-related co-morbidities continue to increase more rapidly as causes of death among HIV-infected individuals than in those without HIV infection, highlighting the need for targeting prevention measures and surveillance for chronic diseases among those patients.

  1. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data.

    Directory of Open Access Journals (Sweden)

    Adelzon A Paula

    Full Text Available INTRODUCTION: After antiretroviral therapy (ART became available, there was a decline in the number of deaths in persons infected with HIV. Thereafter, there was a decrease in the proportion of deaths attributed to opportunistic infections and an increase in the proportion of deaths attributed to chronic comorbidities. Herein we extend previous observations from a nationwide survey on temporal trends in causes of death in HIV-infected patients in Brazil. METHODS: We describe temporal trends in causes of death among adults who had HIV/AIDS listed in the death certificate to those who did not. All death certificates issued in Brazil from 1999 to 2011 and listed in the national mortality database were included. Generalized linear mixed-effects logistic models were used to study temporal trends in proportions. RESULTS: In the HIV-infected population, there was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer, external causes, cardiovascular diseases (CVD and diabetes mellitus (DM, respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For tuberculosis (TB, there was an adjusted average increase of 0.3%/year and a decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared to 1999, the odds ratio (OR for cancer, external causes, CVD, DM, or TB in the HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non-HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67. Interactions between year as a continuous or categorical variable and HIV were significant (p<0.001 for all conditions, except for DM when year was considered as a continuous variable (p = 0.76. CONCLUSIONS: Non HIV-related co-morbidities continue to increase more rapidly as causes of death among HIV-infected individuals than in those without HIV infection, highlighting the need for targeting prevention measures and surveillance for chronic diseases among those patients.

  2. Adapting the minority stress model: associations between gender non-conformity stigma, HIV-related stigma and depression among men who have sex with men in South India.

    Science.gov (United States)

    Logie, Carmen H; Newman, Peter A; Chakrapani, Venkatesan; Shunmugam, Murali

    2012-04-01

    Marginalization and stigmatization heighten the vulnerability of sexual minorities to inequitable mental health outcomes. There is a dearth of information regarding stigma and mental health among men who have sex with men (MSM) in India. We adapted Meyer's minority stress model to explore associations between stigma and depression among MSM in South India. The study objective was to examine the influence of sexual stigma, gender non-conformity stigma (GNS) and HIV-related stigma (HIV-S) on depression among MSM in South India. A cross-sectional survey was administered to MSM in urban (Chennai) (n=100) and semi-urban (Kumbakonam) (n=100) locations in Tamil Nadu. The majority of participants reported moderate/severe depression scores. Participants in Chennai reported significantly higher levels of GNS, social support and resilient coping, and lower levels of HIV-S and depression, than participants in Kumbakonam. Hierarchical block regression analyses were conducted to measure associations between independent (GNS, HIV-S), moderator (social support, resilient coping) and dependent (depression) variables. Sexual stigma was not included in regression analyses due to multicollinearity with GNS. The first regression analyses assessed associations between depression and stigma subtypes. In Chennai, perceived GNS was associated with depression; in Kumbakonam enacted/perceived GNS and vicarious HIV-S were associated with depression. In the moderation analyses, overall GNS and HIV-S scores (subtypes combined) accounted for a significant amount of variability in depression in both locations, although HIV-S was only a significant predictor in Kumbakonam. Social support and resilient coping were associated with lower depression but did not moderate the influence of HIV-S or GNS on depression. Differences in stigma, coping, social support and depression between locations highlight the salience of considering geographical context in stigma analyses. Associations between HIV-S and

  3. HIV-related risk behaviours and the correlates among rickshaw pullers of Kamrangirchar, Dhaka, Bangladesh: a cross-sectional study using probability sampling

    Directory of Open Access Journals (Sweden)

    Ravari Shahrzad

    2009-03-01

    Full Text Available Abstract Background National HIV serological and behavioural surveillance of Bangladesh repeatedly demonstrated a very high proportion of rickshaw pullers in Dhaka city, having sex with female sex workers (FSWs and using illicit substances. However, no study has been conducted to identify the correlates of having sex with FSWs among this population. This study aimed to describe behavioural profile of rickshaw pullers in Dhaka city using probability samples and to identify the correlates for having sex with FSWs in order to focus HIV prevention intervention. Methods Six hundred rickshaw pullers were randomly selected from rickshaw garages in the Kamrangirchar area, the single largest slum cluster of Dhaka, Bangladesh, during March–April 2008 using the Proportion Probability to Size method. Participants were interviewed, with a response rate of 99.2% (n = 595, using a structured questionnaire and asked about illicit substance use, sexual behaviour and risk perception for HIV and sexually transmitted diseases. Independent predictors of having sex with FSWs were analysed by multivariate analysis. A qualitative study was subsequently conducted with 30 rickshaw pullers to supplement the findings of the initial survey. Results The proportion of survey respondents who had sex with FSWs and those who used illicit substances in the previous 12 months period were 7.9% and 24.9%, respectively, much lower than the results achieved in the 2003–04 behavioural surveillance (72.8% and 89.9%, respectively. Multivariate analysis revealed the characteristics of younger age, being never married, living alone with family remaining in other districts and using illicit substances in the previous 12 months were significantly associated with having sex with FSWs. Conclusion HIV-related risk behaviour of our study population of the rickshaw pullers was lower than what has been suggested by the results of behavioural surveillance. While this discrepancy should be

  4. End-Point Contact Force Control with Quantitative Feedback Theory for Mobile Robots

    Directory of Open Access Journals (Sweden)

    Shuhuan Wen

    2012-12-01

    Full Text Available Robot force control is an important issue for intelligent mobile robotics. The end-point stiffness of a robot is a key and open problem in the research community. The control strategies are mostly dependent on both the specifications of the task and the environment of the robot. Due to the limited stiffness of the end-effector, we may adopt inherent torque to feedback the oscillations of the controlled force. This paper proposes an effective control strategy which contains a controller using quantitative feedback theory. The nested loop controllers take into account the physical limitation of the system's inner variables and harmful interference. The biggest advantage of the method is its simplicity in both the design process and the implementation of the control algorithm in engineering practice. Taking the one-link manipulator as an example, numerical experiments are carried out to verify the proposed control method. The results show the satisfactory performance.

  5. Sensitive endpoints in extended one-generation reproductive toxicity study versus two generation?

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    Increasing pressure is exerted by some stakeholders to replace the current “golden standard”, two-generation study (OECD TG 416), by an extended one-generation reproductive toxicity study (EOGRTS), because this would considerably reduce the number of animals and other costs involved in these leng......Increasing pressure is exerted by some stakeholders to replace the current “golden standard”, two-generation study (OECD TG 416), by an extended one-generation reproductive toxicity study (EOGRTS), because this would considerably reduce the number of animals and other costs involved...... during critical period of development in contrast to the parental generation. Retrospective analysis of available two-generation studies, however, indicate that the assessment included in the study of other endpoints in the male offspring such as histopathology of reproductive organs and semen quality...

  6. On the Higher Moments of Particle Multiplicity, Chemical Freeze-Out, and QCD Critical Endpoint

    Directory of Open Access Journals (Sweden)

    A. Tawfik

    2013-01-01

    Full Text Available We calculate the first six nonnormalized moments of particle multiplicity within the framework of the hadron resonance gas model. In terms of the lower order moments and corresponding correlation functions, general expressions of higher order moments are derived. Thermal evolution of the first four normalized moments and their products (ratios are studied at different chemical potentials, so that it is possible to evaluate them at chemical freeze-out curve. It is found that a nonmonotonic behaviour reflecting the dynamical fluctuation and strong correlation of particles starts to appear from the normalized third order moment. We introduce novel conditions for describing the chemical freeze-out curve. Although the hadron resonance gas model does not contain any information on the criticality related to the chiral dynamics and singularity in the physical observables, we are able to find out the location of the QCD critical endpoint at μ ~ 350  MeV and temperature T ~ 162  MeV.

  7. Correlation of hip fracture with other fracture types: Toward a rational composite hip fracture endpoint.

    Science.gov (United States)

    Colón-Emeric, Cathleen; Pieper, Carl F; Grubber, Janet; Van Scoyoc, Lynn; Schnell, Merritt L; Van Houtven, Courtney Harold; Pearson, Megan; Lafleur, Joanne; Lyles, Kenneth W; Adler, Robert A

    2015-12-01

    With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between 1999 and 2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics were used to describe the correlation between each fracture type and hip fracture within individuals, without regard to the timing of the events. 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, the rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, pfractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider the use of a composite endpoint to better estimate hip fracture risk. Published by Elsevier Inc.

  8. Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

    Science.gov (United States)

    Mashock, Michael J; Zanon, Tyler; Kappell, Anthony D; Petrella, Lisa N; Andersen, Erik C; Hristova, Krassimira R

    2016-01-01

    Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits

  9. THE SENSITIVITY OF ENDPOINT FORCES PRODUCED BY THE EXTRINSIC MUSCLES OF THE THUMB TO POSTURE

    Science.gov (United States)

    Goehler, Craig M.; Murray, Wendy M.

    2010-01-01

    This study utilizes a biomechanical model of the thumb to estimate the force produced at the thumb-tip by each of the four extrinsic muscles. We used the principle of virtual work to relate joint torques produced by a given muscle force to the resulting endpoint force and compared the results to two separate cadaveric studies. When we calculated thumb-tip forces using the muscle forces and thumb postures described in the experimental studies, we observed large errors. When relatively small deviations from experimentally reported thumb joint angles were allowed, errors in force direction decreased substantially. For example, when thumb posture was constrained to fall within ±15° of reported joint angles, simulated force directions fell within experimental variability in the proximal-palmar plane for all four muscles. Increasing the solution space from ±1° to an unbounded space produced a sigmoidal decrease in error in force direction. Changes in thumb posture remained consistent with a lateral pinch posture, and were generally consistent with each muscle’s function. Altering thumb posture alters both the components of the Jacobian and muscle moment arms in a nonlinear fashion, yielding a nonlinear change in thumb-tip force relative to muscle force. These results explain experimental data that suggest endpoint force is a nonlinear function of muscle force for the thumb, support the continued use of methods that implement linear transformations between muscle force and thumb-tip force for a specific posture, and suggest the feasibility of accurate prediction of lateral pinch force in situations where joint angles can be measured accurately. PMID:20303085

  10. Use of sublethal endpoints in sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Chris G.; Brunson, Eric L.; Dwyer, F. James; Hardesty, Douglas K.; Kemble, Nile E.

    1998-01-01

    Short-term sediment toxicity tests that only measure effects on survival can be used to identify high levels of contamination but may not be able to identify marginally contaminated sediments. The objective of the present study was to develop a method for determining the potential sublethal effects of contaminants associated with sediment on the amphipod Hyalella azteca (e.g., reproduction). Exposures to sediment were started with 7- to 8-d-old amphipods. On day 28, amphipods were isolated from the sediment and placed in water-only chambers where reproduction was measured on day 35 and 42. Typically, amphipods were first in amplexus at about day 21 to 28 with release of the first brood between day 28 to 42. Endpoints measured included survival (day 28, 35, and 42), growth (as length and weight on day 28 and 42), and reproduction (number of young/female produced from day 28 to 42). This method was used to evaluate a formulated sediment and field-collected sediments with low to moderate concentrations of contaminants. Survival of amphipods in these sediments was typically >85% after the 28-d sediment exposures and the 14-d holding period in water to measure reproduction. Reproduction was more variable than growth; hence, more replicates might be needed to establish statistical differences among treatments. Previous studies have demonstrated that growth of H. azteca in sediment tests often provides unique information that can be used to discriminate toxic effects of exposure to contaminants. Either length or weight can be measured in sediment tests with H. azteca. However, additional statistical options are available if length is measured on individual amphipods, such as nested analysis of variance that can account for variance in length within replicates. Ongoing water-only studies testing select contaminants will provide additional data on the relative sensitivity and variability of sublethal endpoints in toxicity tests with H. azteca.

  11. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Directory of Open Access Journals (Sweden)

    Amory Koch

    Full Text Available Acute radiation sickness (ARS following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS developed at the Veterinary Sciences Department (VSD of the Armed Forces Radiobiology Research Institute (AFRRI to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1, which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated, 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors. In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

  12. Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Rosa Correa, Albertina Xavier da [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Roerig, Leonardo Rubi [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Verdinelli, Miguel A. [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Cotelle, Sylvie [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Ferard, Jean-Francois [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Radetski, Claudemir Marcos [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil)]. E-mail: radetski@univali.br

    2006-03-15

    In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd{sup 2+} that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity > biomass > germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values.

  13. A neutralization assay for respiratory syncytial virus using a quantitative PCR-based endpoint assessment

    Science.gov (United States)

    2013-01-01

    Background Few studies have used quantitative polymerase chain reaction (qPCR) as an approach to measure virus neutralization assay endpoints. Its lack of use may not be surprising considering that sample nucleic acid extraction and purification can be expensive, labor-intensive, and rate-limiting. Methods Virus/antibody mixtures were incubated for one hour at 37°C and then transferred to Vero cell monolayers in a 96-well plate format. At 24 (or 48) hours post-infection, we used a commercially available reagent to prepare cell lysates amenable to direct analysis by one-step SYBR Green quantitative reverse transcription PCR using primers specific for the RSV-N gene, thereby obviating the need for cumbersome RNA extraction and purification. The neutralization titer was defined as the reciprocal of the highest dilution needed to inhibit the PCR signal by 90% when compared with the mean value observed in virus control wells in the absence of neutralizing antibodies. Results We have developed a qPCR-based neutralization assay for human respiratory syncytial virus. Due to the sensitivity of qPCR in detecting virus replication, endpoints may be assessed as early as 24 hours post-infection. In addition, the dynamic range of qPCR provides a basis for the assay to be relatively robust to perturbations in input virus dose (i.e., the assay is in compliance with the Percentage Law). Conclusions This qPCR-based neutralization assay is suitable for automated high-throughput applications. In addition, our experimental approach may be generalizable for the rapid development of neutralization assays for other virus families. PMID:23767960

  14. Classical and biochemical endpoints in the evaluation of phytotoxic effects caused by the herbicide trichloroacetate.

    Science.gov (United States)

    Radetski; Cotelle; Férard

    2000-11-01

    Three terrestrial plant species, oat (Avena sativa ), Chinese cabbage (Brassica campestris cv. chinensis) and lettuce (Lactuca sativa), were exposed to different concentrations of herbicide TCA (sodium trichloroacetate) in a growth test according to guideline OECD # 208. Classical (i.e. germination and biomass) and biochemical (i.e., antioxydant enzyme activities) endpoints were investigated. Germination rate decreased significantly at 3.9 mg TCA kg dry soil(-1) (for oat and lettuce) and 62.5 mg TCA kg dry soil(-1) (for Chinese cabbage). Biomass decreased significantly only at 1.9 mg TCA kg dry soil(-1) (for oat and lettuce) and 15.6 mg TCA kg dry soil(-1) (for Chinese cabbage). The activities of superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), peroxidase (EC 1.11.1.7) and glutathione reductase (EC 1.6.4.2) increased significantly at the lowest concentration of TCA tested, i.e. 0.03 mg TCA kg dry soil(-1) (for oat and lettuce) and 0.48 mg TCA kg dry soil(-1) (for Chinese cabbage). Our results showed a ranking of sensitivity among the different endpoints for the three plant species: enzyme activities>biomass>germination rate. The increase in antioxidant enzyme activities observed in this study ensured the detoxification of increased levels of active oxygen species, and presumably prevented the plants from undergoing oxidative stress damage. Thus, the use of enzyme activities will permit the detection of early injury in plant growth testing.

  15. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients

    DEFF Research Database (Denmark)

    Vandenhende, Marie-Anne; Ingle, Suzanne; May, Margaret

    2015-01-01

    BACKGROUND: The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. OBJECTIVE: Assess the association of different levels o...

  16. Sodium chloride as a reference substance for the three growth endpoints used in the Lemna minor L. (1753 test

    Directory of Open Access Journals (Sweden)

    Aline Andrade Godoy

    2017-01-01

    Full Text Available Lemna sp. growth inhibition test standardized protocols suggest the use of compounds such as 3,5-dichlorophenol as reference substances for checking the test organism’s sensitivity routinely. However, this and other recommended chemicals present risks to human health and to the environment. Sodium chloride (NaCl appears as a less toxic alternative reference substance which has been successfully used in routine ecotoxicological tests. However, the evaluation of this compound in multiple growth endpoints used in the L. minor test, which is required for recommending it as a reference substance for this test organism, has not yet been reported. In the present study, NaCl was tested with L. minor for the growth endpoints frond number, total frond area and fresh weight. Results showed acceptable sensitivity and reproducibility (coefficient of variance < 15.0% for all three of the measured endpoints. Statistically significant differences were observed between the EC50 values calculated based on the three endpoints (p < 0.05. Total frond area was the most sensitive one, with average EC50 value of 2742.80 ± 245.7 mg L-1. It was anticipated that NaCl can be a suitable alternative reference substance and that total frond area should be the endpoint of choice for sensitivity toxicity tests using NaCl.

  17. Nutrient reference value: non-communicable disease endpoints--a conference report.

    Science.gov (United States)

    Lupton, J R; Blumberg, J B; L'Abbe, M; LeDoux, M; Rice, H B; von Schacky, C; Yaktine, A; Griffiths, J C

    2016-03-01

    scientific evidence does exist to confirm a relationship between the intake of a specific bioactive constituent and enhanced health conditions or reduced risk of a chronic disease. Further, research on the putative mechanisms of action of various classes of bioactives is supported by national and pan-national government agencies, and academic institutions, as well as functional food and dietary supplement manufacturers. Consumers are becoming educated and are seeking to purchase products containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects or to avoid exceeding the upper level (UL). When one lacks an essential nutrient, overt deficiency with concomitant physiological determents and eventually death are expected. The absence of bioactive substances from the diet results in suboptimal health, e.g., poor cellular and/or physiological function, which is relative and not absolute. Regrettably at this time, there is no DRI process to evaluate bioactives, although a recent workshop convened by the National Institutes of Health (Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs); March 10-11, 2015; http://health.gov/dietaryguidelines/dri/ ) did explore the process to develop DVs for nutrients, the lack of which result in increased risk of chronic disease (non-communicable disease) endpoints. A final report is expected soon. This conference (CRN-International Scientific Symposium; "Nutrient Reference Value-Non-Communicable Disease (NRV-NCD) Endpoints," 20 November in Kronberg, Germany; http://www.crn-i.ch/2015symposium/ ) explores concepts related to the Codex NRV process, the public health opportunities in setting NRVs for bioactive constituents, and further research and details on the specific class of bioactives, n-3 long-chain polyunsaturated fatty acids (also termed omega-3 fatty

  18. Blood plasma clinical-chemical parameters as biomarker endpoints for organohalogen contaminant exposure in Norwegian raptor nestlings

    DEFF Research Database (Denmark)

    Sonne, Christian; Bustnes, Jan O.; Herzke, Dorte

    2012-01-01

    ), golden eagle (n=12) and white-tailed eagle (n=36) nestlings during three consecutive breeding seasons. We found that blood plasma concentrations of calcium, sodium, creatinine, cholesterol, albumin, total protein, urea, inorganic phosphate, protein:creatinine, urea:creatinine and uric acid...

  19. Delayed onset of ambulation in boys with Duchenne muscular dystrophy : Potential use as an endpoint in clinical trials

    NARCIS (Netherlands)

    Gissy, Jacob J.; Johnson, Teresa; Fox, Deborah J.; Kumar, Anil; Ciafaloni, Emma; van Essen, Anthonie J.; Peay, Holly L.; Martin, Ann; Lucas, Ann; Finkel, Richard S.

    2017-01-01

    Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor and cognitive development, including delayed onset of ambulation. Data on age when loss of independent ambulation occurs are well established for DMD; however, age at onset of walking has not been well described. We

  20. Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: A comprehensive review of the literature

    NARCIS (Netherlands)

    B. Schoser; Fong, E. (Edward); Geberhiwot, T. (Tarekegn); Hughes, D. (Derralynn); Kissel, J.T. (John T.); Madathil, S.C. (Shyam C.); Orlikowski, D. (David); Polkey, M.I. (Michael I.); M. Roberts (Mark); H.A.W.M. Tiddens (Harm); Young, P. (Peter)

    2017-01-01

    textabstractRespiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle

  1. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Cromheecke, M. E.; de Jonge, E.; Prins, M. H.; de Mol, B. J.; Briët, E.; Büller, H. R.

    1999-01-01

    Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most

  2. An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

    Directory of Open Access Journals (Sweden)

    Patrick P J Phillips

    Full Text Available It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

  3. Population-relevant endpoints in the evaluation of endocrine-active substances (EAS) for ecotoxicological hazard and risk assessment.

    Science.gov (United States)

    Marty, Mary S; Blankinship, Amy; Chambers, Janice; Constantine, Lisa; Kloas, Werner; Kumar, Anupama; Lagadic, Laurent; Meador, James; Pickford, Daniel; Schwarz, Tamar; Verslycke, Tim

    2017-03-01

    For ecotoxicological risk assessment, endocrine disruptors require the establishment of an endocrine mode of action (MoA) with a plausible link to a population-relevant adverse effect. Current ecotoxicity test methods incorporate mostly apical endpoints although some also include mechanistic endpoints, subcellular-through-organ level, which can help establish an endocrine MoA. However, the link between these endpoints and adverse population-level effects is often unclear. The case studies of endocrine-active substances (EAS) (tributyltin, ethinylestradiol, perchlorate, trenbolone, propiconazole, and vinclozolin) evaluated from the Society of Environmental Toxicology and Chemistry (SETAC) Pellston Workshop ® "Ecotoxicological Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)" were used to evaluate the population relevance of toxicity endpoints in various taxa according to regulatory endocrine-disruptor frameworks such as the Organisation for Economic Co-operation and Development (OECD) Conceptual Framework for Testing and Assessment of Endocrine Disruptors. A wide variety of potentially endocrine-relevant endpoints were identified for mollusks, fish, amphibians, birds, and mammals, although the strength of the relationship between test endpoints and population-level effects was often uncertain. Furthermore, testing alone is insufficient for assessing potential adaptation and recovery processes in exposed populations. For this purpose, models that link effects observed in laboratory tests to the dynamics of wildlife populations appear to be necessary, and their development requires reliable and robust data. As our understanding of endocrine perturbations and key event relationships improves, adverse population-level effects will be more easily and accurately predicted. Integr Environ Assess Manag 2017;13:317-330. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of

  4. Reducing HIV-related risk and mental health problems through a client-centred psychosocial intervention for vulnerable adolescents in Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Nrupa Jani

    2016-07-01

    Full Text Available Introduction: Ethiopia is experiencing an increasingly urban HIV epidemic, alongside a rise in urban adolescent migration. Adolescent migrants are often confronted by unique social challenges, including living in a difficult environment, abuse and mental health problems. These issues can increase adolescents’ vulnerability to HIV and compromise their capacity to protect themselves and others from HIV. We piloted and assessed the effects of a targeted psychosocial intervention to reduce mental health problems and improve HIV-related outcomes among migrant adolescents in Addis Ababa. Methods: A pre- and post-comparison design was used in a cohort of 576 female and 154 male migrant adolescents aged 15 to 18 years in Addis Ababa receiving services from two service delivery organizations, Biruh Tesfa and Retrak. We implemented a three-month client-centred, counsellor-delivered psychosocial intervention, based on findings from formative research among the same target population, to address participants’ increased vulnerability to HIV. The intervention package comprised individual, group and creative arts therapy counselling sessions. Key outcome indicators included anxiety, depression, aggressive behaviour, attention problems, social problems, knowledge of HIV, safer sex practices and use of sexual health services. Longitudinal data analysis (McNemar test and random effects regression was used to assess changes over time in key indicators by gender. Results: For females, aggressive behaviour decreased by 60% (adjusted odds ratio (AOR: 0.4 (0.25 to 0.65 and any mental health problem decreased by 50% (AOR: 0.5 (0.36 to 0.81 from baseline to end line. In addition, knowledge of HIV increased by 60% (AOR: 1.6 (1.08 to 2.47, knowledge of a place to test for HIV increased by 70% (AOR: 1.7 (1.12 to 2.51 and HIV testing increased by 80% (AOR: 1.8 (1.13 to 2.97. For males, HIV knowledge increased by 110% (AOR: 2.1 (1.1 to 3.94, knowledge of a place to test

  5. Reducing HIV-related risk and mental health problems through a client-centred psychosocial intervention for vulnerable adolescents in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Jani, Nrupa; Vu, Lung; Kay, Lynnette; Habtamu, Kassahun; Kalibala, Samuel

    2016-01-01

    Ethiopia is experiencing an increasingly urban HIV epidemic, alongside a rise in urban adolescent migration. Adolescent migrants are often confronted by unique social challenges, including living in a difficult environment, abuse and mental health problems. These issues can increase adolescents' vulnerability to HIV and compromise their capacity to protect themselves and others from HIV. We piloted and assessed the effects of a targeted psychosocial intervention to reduce mental health problems and improve HIV-related outcomes among migrant adolescents in Addis Ababa. A pre- and post-comparison design was used in a cohort of 576 female and 154 male migrant adolescents aged 15 to 18 years in Addis Ababa receiving services from two service delivery organizations, Biruh Tesfa and Retrak. We implemented a three-month client-centred, counsellor-delivered psychosocial intervention, based on findings from formative research among the same target population, to address participants' increased vulnerability to HIV. The intervention package comprised individual, group and creative arts therapy counselling sessions. Key outcome indicators included anxiety, depression, aggressive behaviour, attention problems, social problems, knowledge of HIV, safer sex practices and use of sexual health services. Longitudinal data analysis (McNemar test and random effects regression) was used to assess changes over time in key indicators by gender. For females, aggressive behaviour decreased by 60% (adjusted odds ratio (AOR): 0.4 (0.25 to 0.65)) and any mental health problem decreased by 50% (AOR: 0.5 (0.36 to 0.81)) from baseline to end line. In addition, knowledge of HIV increased by 60% (AOR: 1.6 (1.08 to 2.47)), knowledge of a place to test for HIV increased by 70% (AOR: 1.7 (1.12 to 2.51)) and HIV testing increased by 80% (AOR: 1.8 (1.13 to 2.97)). For males, HIV knowledge increased by 110% (AOR: 2.1 (1.1 to 3.94)), knowledge of a place to test for HIV increased by 290% (AOR: 3.9 (1

  6. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hailay Abrha Gesesew

    Full Text Available Late presentation for human immunodeficiency virus (HIV care is a major impediment for the success of antiretroviral therapy (ART outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care.Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value.Ten studies from low- and middle- income countries met the search criteria, including six (6 and four (4 case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5 of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%.High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling

  7. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

    Science.gov (United States)

    Gesesew, Hailay Abrha; Tesfay Gebremedhin, Amanuel; Demissie, Tariku Dejene; Kerie, Mirkuzie Woldie; Sudhakar, Morankar; Mwanri, Lillian

    2017-01-01

    Late presentation for human immunodeficiency virus (HIV) care is a major impediment for the success of antiretroviral therapy (ART) outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome) is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care. Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI) data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value. Ten studies from low- and middle- income countries met the search criteria, including six (6) and four (4) case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5) of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%). High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling patients

  8. How much gets there and what does it do?: The need for better pharmacokinetic and pharmacodynamic endpoints in contemporary drug discovery and development.

    Science.gov (United States)

    Workman, Paul

    2003-01-01

    Drug discovery is an expensive, slow and high risk enterprise. Only one in ten of the agents that enter clinical development is successful, with an average cost of US dollars 500-800 million and a typical time-scale of 10-15 years from preclinical discovery research to regulatory approval. On the other hand, many new targets are emerging from genome sequencing and the improved understanding of molecular pathology. Also, new technologies are increasing the speed and improving the efficiency of drug discovery. These new advances should facilitate progress towards the development of personalised therapies that are targeted to the genetics and molecular pathology of individual patients. The availability of pharmacokinetic (PK) and pharmacodynamic (PD) endpoints is absolutely critical to modern drug development. They allow us to understand how much of the drug gets there (into the body and ideally to the target cells) and what it does (with respect to modulation of the molecular target and the cognate biochemical pathways and downstream biological effects). PK and PD endpoints allow us to construct a pharmacological audit trail, so that all of the successive stages from drug administration through to biological effects and clinical outcome can be monitored and interpreted. This in turn provides a rational basis for decision making, e.g. stop/go, during development. An understanding of PK/PD relationships also gives us s basis for selecting the optimal drug dose and schedule. Better, less invasive methods are required. Developments in molecular/functional imaging show promise and current examples are provided.

  9. CaFE: a tool for binding affinity prediction using end-point free energy methods.

    Science.gov (United States)

    Liu, Hui; Hou, Tingjun

    2016-07-15

    Accurate prediction of binding free energy is of particular importance to computational biology and structure-based drug design. Among those methods for binding affinity predictions, the end-point approaches, such as MM/PBSA and LIE, have been widely used because they can achieve a good balance between prediction accuracy and computational cost. Here we present an easy-to-use pipeline tool named Calculation of Free Energy (CaFE) to conduct MM/PBSA and LIE calculations. Powered by the VMD and NAMD programs, CaFE is able to handle numerous static coordinate and molecular dynamics trajectory file formats generated by different molecular simulation packages and supports various force field parameters. CaFE source code and documentation are freely available under the GNU General Public License via GitHub at https://github.com/huiliucode/cafe_plugin It is a VMD plugin written in Tcl and the usage is platform-independent. tingjunhou@zju.edu.cn. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. An end-point method based on graphene oxide for RNase H analysis and inhibitors screening.

    Science.gov (United States)

    Zhao, Chuan; Fan, Jialong; Peng, Lan; Zhao, Lijian; Tong, Chunyi; Wang, Wei; Liu, Bin

    2017-04-15

    As a highly conserved damage repair protein, RNase H can hydrolysis DNA-RNA heteroduplex endonucleolytically and cleave RNA-DNA junctions as well. In this study, we have developed an accurate and sensitive RNase H assay based on fluorophore-labeled chimeric substrate hydrolysis and the differential affinity of graphene oxide on RNA strand with different length. This end-point measurement method can detect RNase H in a range of 0.01 to 1 units /mL with a detection limit of 5.0×10 -3 units/ mL under optimal conditions. We demonstrate the utility of the assay by screening antibiotics, resulting in the identification of gentamycin, streptomycin and kanamycin as inhibitors with IC 50 of 60±5µM, 70±8µM and 300±20µM, respectively. Furthermore, the assay was reliably used to detect RNase H in complicated biosamples and found that RNase H activity in tumor cells was inhibited by gentamycin and streptomycin sulfate in a concentration-dependent manner. The average level of RNase H in serums of HBV infection group was similar to that of control group. In summary, the assay provides an alternative tool for biochemical analysis for this enzyme and indicates the feasibility of high throughput screening inhibitors of RNase H in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. An information-theoretic approach for the evaluation of surrogate endpoints based on causal inference.

    Science.gov (United States)

    Alonso, Ariel; Van der Elst, Wim; Molenberghs, Geert; Buyse, Marc; Burzykowski, Tomasz

    2016-09-01

    In this work a new metric of surrogacy, the so-called individual causal association (ICA), is introduced using information-theoretic concepts and a causal inference model for a binary surrogate and true endpoint. The ICA has a simple and appealing interpretation in terms of uncertainty reduction and, in some scenarios, it seems to provide a more coherent assessment of the validity of a surrogate than existing measures. The identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is proposed to study the behavior of the ICA on the previous region. The method is illustrated using data from the Collaborative Initial Glaucoma Treatment Study. A newly developed and user-friendly R package Surrogate is provided to carry out the evaluation exercise. © 2016, The International Biometric Society.

  12. Determining significant endpoints for ecological risk analyses. 1997 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, T.G.; Congdon, J.; Rowe, C.; Scott, D. [Univ. of Georgia, Aiken, SC (US). Savannah River Ecology Lab.; Bedford, J.; Whicker, F.W. [Colorado State Univ., Fort Collins, CO (US)

    1997-11-01

    'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses that reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'

  13. Natural Gas Residual Fluids: Sources, Endpoints, and Organic Chemical Composition after Centralized Waste Treatment in Pennsylvania.

    Science.gov (United States)

    Getzinger, Gordon J; O'Connor, Megan P; Hoelzer, Kathrin; Drollette, Brian D; Karatum, Osman; Deshusses, Marc A; Ferguson, P Lee; Elsner, Martin; Plata, Desiree L

    2015-07-21

    Volumes of natural gas extraction-derived wastewaters have increased sharply over the past decade, but the ultimate fate of those waste streams is poorly characterized. Here, we sought to (a) quantify natural gas residual fluid sources and endpoints to bound the scope of potential waste stream impacts and (b) describe the organic pollutants discharged to surface waters following treatment, a route of likely ecological exposure. Our findings indicate that centralized waste treatment facilities (CWTF) received 9.5% (8.5 × 10(8) L) of natural gas residual fluids in 2013, with some facilities discharging all effluent to surface waters. In dry months, discharged water volumes were on the order of the receiving body flows for some plants, indicating that surface waters can become waste-dominated in summer. As disclosed organic compounds used in high volume hydraulic fracturing (HVHF) vary greatly in physicochemical properties, we deployed a suite of analytical techniques to characterize CWTF effluents, covering 90.5% of disclosed compounds. Results revealed that, of nearly 1000 disclosed organic compounds used in HVHF, only petroleum distillates and alcohol polyethoxylates were present. Few analytes targeted by regulatory agencies (e.g., benzene or toluene) were observed, highlighting the need for expanded and improved monitoring efforts at CWTFs.

  14. The Endpoint Hypothesis: A Topological-Cognitive Assessment of Geographic Scale Movement Patterns

    Science.gov (United States)

    Klippel, Alexander; Li, Rui

    Movement patterns of individual entities at the geographic scale are becoming a prominent research focus in spatial sciences. One pertinent question is how cognitive and formal characterizations of movement patterns relate. In other words, are (mostly qualitative) formal character