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Find video protocols related to scientific articles indexed in Pubmed.
Tuberculosis preventive therapy: an underutilised strategy to reduce individual risk of TB and contribute to TB control.
S. Afr. Med. J.
PUBLISHED: 04-06-2014
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Tuberculosis (TB) remains a global health problem, and South Africa (SA) has one of the world's worst TB epidemics. The World Health Organization (WHO) estimated in 1999 that one-third of the world's population was latently infected with TB. In SA up to 88% of HIV-uninfected young adults (31 - 35 years) are latently infected with TB. In the most recent meta-analysis, 6 - 12 months of isoniazid preventive therapy (IPT) was associated with a lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 - 0.85), with the greatest benefit among individuals with a positive tuberculin skin test (TST) (RR 0.38; 95% CI 0.25 - 0.57). A clinical trial of IPT given with antiretroviral therapy (ART) for 12 months reduced TB incidence by 37% compared with ART alone (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94). The effect of IPT is limited in high-burden countries. IPT for 36 months v. 6 months reduced TB incidence among HIV-positive, TST-positive participants by 74% (HR 0.26; 95% CI 0.09 - 0.80). A study of more than 24 000 goldminers confirmed that IPT is safe, with only 0.5% experiencing adverse events. A meta-analysis of studies of IPT since 1951 did not show an increased risk of developing resistance. Alternative TB preventive therapy regimens, including high-dose isoniazid and rifapentine given weekly for 3 months, have been shown to have similar efficacy to IPT. Mathematical modelling suggests that scaling up continuous IPT targeted to HIV-positive persons, when used in combination with other treatment and prevention strategies, may substantially improve TB control.
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Durable HIV RNA resuppression after virologic failure while remaining on a first-line regimen: a cohort study.
Trop. Med. Int. Health
PUBLISHED: 03-04-2014
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Adherence interventions are a recommended strategy to salvage failing antiretroviral therapy without regimen change. We assessed the durability of resuppression when using this approach. Of 300 patients who resuppressed on the same regimen (41% of all those with virologic failure), 148 (45%) remained suppressed during follow-up for a median of 2.4 years (interquartile range [IQR]: 1.1, 4.0). Resuppression can be durable following viraemia without a switch in antiretroviral therapy regimen.
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Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.
Lancet Infect Dis
PUBLISHED: 02-20-2014
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The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data.
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A trial of mass isoniazid preventive therapy for tuberculosis control.
N. Engl. J. Med.
PUBLISHED: 01-24-2014
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Tuberculosis is epidemic among workers in South African gold mines. We evaluated an intervention to interrupt tuberculosis transmission by means of mass screening that was linked to treatment for active disease or latent infection.
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Uptake of Genital Mucosal Sampling in HVTN 097, a Phase 1b HIV Vaccine Trial in South Africa.
PLoS ONE
PUBLISHED: 01-01-2014
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Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n?=?70, 33%), Cape Town (n?=?68, 32%) and Klerksdorp (n?=?73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n?=?149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p?=?0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p?=?0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies.
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Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.
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Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses.
PLoS ONE
PUBLISHED: 01-01-2014
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Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses.
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Four models of HIV counseling and testing: utilization and test results in South Africa.
PLoS ONE
PUBLISHED: 01-01-2014
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HIV Counseling and Testing (HCT) is the point-of-entry for pathways of HIV care and prevention. However, HCT is not reaching many who are HIV infected and this may be related to the HCT provision model. We describe HCT utilization and HIV diagnosis using four models of HCT delivery: clinic-based, urban mobile, rural mobile, and stand-alone.
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Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection.
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High tuberculosis prevalence in a South African prison: the need for routine tuberculosis screening.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis is a major health concern in prisons, particularly where HIV prevalence is high. Our objective was to determine the undiagnosed pulmonary tuberculosis ("undiagnosed tuberculosis") prevalence in a representative sample of prisoners in a South African prison. In addition we investigated risk factors for undiagnosed tuberculosis, to explore if screening strategies could be targeted to high risk groups, and, the performance of screening tools for tuberculosis.
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The HVTN503/Phambili HIV vaccine trial: A comparison of younger and older participants.
Int J STD AIDS
PUBLISHED: 10-08-2013
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By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n?=?238) and older participants (n?=?563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p?=?0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p?
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Viral Suppression Following Switch to Second-line Antiretroviral Therapy: Associations With Nucleoside Reverse Transcriptase Inhibitor Resistance and Subtherapeutic Drug Concentrations Prior to Switch.
J. Infect. Dis.
PUBLISHED: 08-13-2013
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Background.?High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.Methods.?Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.Results.?One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ?1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.Conclusions.?Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.
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Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa.
Antivir. Ther. (Lond.)
PUBLISHED: 05-18-2013
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BACKGROUND: Tenofovir disoproxil fumarate (TDF) is increasingly available for patients infected with subtype C HIV-1. This subtype is reported to develop the principle TDF resistance mutation in the HIV reverse transcriptase, K65R, with greater propensity than other subtypes. We sought to describe K65R development during TDF use in a cohort of patients infected with subtype C HIV. METHODS: Using a prospectively followed cohort with 6 monthly HIV RNA assays, we identified virologic failure (defined as an HIV RNA >1000 c/mL) during treatment that included TDF. Residual serum, stored at the time of the HIV RNA assay, was used for consensus sequencing and allele-specific PCR. We assessed prevalence of resistance at failure during TDF-containing treatment and associated factors. RESULTS: Among 1,682 patients on a TDF-containing regimen, 270 developed failure of which 40 were assessed for resistance. By sequencing, the K65R was identified in 5 (12%), major NNRTI mutations in 24 (57%), and the M184V/I in 12 (28%) patients. The K65R was associated with lower HIV RNA at failure (HIV RNA log10 3.3 versus 4.2 c/mL) and prior stavudine exposure. An additional 5 patients had minority K65R populations identified by allele-specific PCR. CONCLUSIONS: These data suggest that the K65R prevalence at virologic failure is moderately higher in our subtype C population than some non-subtype C HIV cohorts. However, we did not find that the K65R was highly selected in HIV-1 subtype C infected patients with up to 6 months of failure of a TDF-containing regimen.
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The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study.
Eur. Respir. J.
PUBLISHED: 04-18-2013
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A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.
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Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-09-2013
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To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care.
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Comparison of laboratory costs of rapid molecular tests and conventional diagnostics for detection of tuberculosis and drug-resistant tuberculosis in South Africa.
BMC Infect. Dis.
PUBLISHED: 02-08-2013
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The World Health Organization has endorsed the use of molecular methods for the detection of TB and drug-resistant TB as a rapid alternative to culture-based systems. In South Africa, the Xpert MTB/Rif assay and the GenoType MTBDRplus have been implemented into reference laboratories for diagnosis of TB and drug-resistance, but their costs have not been fully elucidated.
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Eligibility for isoniazid preventive therapy in South African gold mines.
PLoS ONE
PUBLISHED: 01-01-2013
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The "Thibela TB" cluster randomised trial of community-wide isoniazid preventive therapy (IPT) to reduce tuberculosis incidence in the South African gold mines.
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Comparison of tenofovir, zidovudine, or stavudine as part of first-line antiretroviral therapy in a resource-limited-setting: a cohort study.
PLoS ONE
PUBLISHED: 01-01-2013
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Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT).
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Diagnosing latent tuberculosis in high-risk individuals: rising to the challenge in high-burden areas.
J. Infect. Dis.
PUBLISHED: 10-15-2011
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A key challenge to greater progress in tuberculosis (TB) control is the reservoir of latent TB infection (LTBI), which represents a huge long-lived reservoir of potential TB disease. In parts of Africa, as many as 50% of 15-year-olds and 77%-89% of adults have evidence of LTBI. A second key challenge to TB control is the human immunodeficiency virus (HIV)-associated TB epidemic, and Africa alone accounts for one-quarter of the global burden of HIV-associated TB. HIV co-infection promotes both reactivation TB from LTBI and rapidly progressive primary TB following recent exposure to Mycobacterium tuberculosis. Preventing active TB and tackling latent infection in addition to the Directly Observed Treatment, Short-Course (DOTS) strategy could improve TB control in high-burden settings, especially where there is a high prevalence of HIV co-infection. Current strategies include intensified case finding (ICF), TB infection control, antiretroviral therapy (ART), and isoniazid preventive therapy (IPT). Although ART has been widely rolled out, ICF and IPT have not. A key factor limiting the rollout and effectiveness of IPT and ICF is the limitations of existing tools to both diagnose LTBI and identify those persons most at risk of progressing to active TB. In this review, we examine the obstacles and consider current progress toward the development of new tools to address this pressing global problem.
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Changing predictors of mortality over time from cART start: implications for care.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-31-2011
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To determine predictors of mortality and changes in those predictors over time on combination antiretroviral therapy (cART) in South Africa.
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Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study.
Lancet Infect Dis
PUBLISHED: 05-11-2011
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The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C.
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Cytomegalovirus viremia as a risk factor for mortality prior to antiretroviral therapy among HIV-infected gold miners in South Africa.
PLoS ONE
PUBLISHED: 03-22-2011
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Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV.
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A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).
PLoS ONE
PUBLISHED: 03-01-2011
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The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
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Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.
PLoS Med.
PUBLISHED: 01-18-2011
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The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.
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Contrasting reasons for discontinuation of antiretroviral therapy in workplace and public-sector HIV programs in South Africa.
AIDS Patient Care STDS
PUBLISHED: 01-11-2011
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Abstract We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient-provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition.
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Twelve-monthly versus six-monthly radiological screening for active case-finding of tuberculosis: a randomised controlled trial.
Thorax
PUBLISHED: 11-23-2010
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The incidence of tuberculosis has increased among South African gold miners despite comprehensive control programmes, including a radiological screening programme. No data are available as to the optimal frequency of screening. The aim of this study was to compare 6-monthly and 12-monthly radiological screening for active tuberculosis case-finding.
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Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme.
AIDS
PUBLISHED: 11-17-2010
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To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis (TB) incidence is very high.
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Barriers to implementation of isoniazid preventive therapy in HIV clinics: a qualitative study.
AIDS
PUBLISHED: 11-17-2010
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Despite good evidence that isoniazid preventive therapy (IPT) reduces incidence of tuberculosis among people with HIV infection, implementation of IPT is low. This study aimed to describe barriers to IPT implementation from healthcare provider and patient perspectives in a donor-funded HIV care programme in Gauteng province, South Africa, in which IPT is recommended, but delivery is variable.
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Team up against TB: promoting involvement in Thibela TB, a trial of community-wide tuberculosis preventive therapy.
AIDS
PUBLISHED: 11-17-2010
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To describe a programme of community education and mobilization to promote uptake in a cluster-randomized trial of tuberculosis preventive therapy offered to all members of intervention clusters.
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Adverse events with isoniazid preventive therapy: experience from a large trial.
AIDS
PUBLISHED: 11-17-2010
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We describe isoniazid-related adverse events in Thibela TB, a cluster-randomized study of community-wide isoniazid preventive therapy (IPT) among gold miners in South Africa, where HIV prevalence is estimated at 30%.
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Symptom and chest radiographic screening for infectious tuberculosis prior to starting isoniazid preventive therapy: yield and proportion missed at screening.
AIDS
PUBLISHED: 11-17-2010
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This analysis describes the prevalence of and risk factors for tuberculosis at screening prior to isoniazid preventive therapy (IPT); the additional yield of tuberculosis using chest radiography versus symptoms alone, and risk factors for tuberculosis missed by screening.
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Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial.
Lancet
PUBLISHED: 10-07-2010
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Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission.
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Thibela TB: design and methods of a cluster randomised trial of the effect of community-wide isoniazid preventive therapy on tuberculosis amongst gold miners in South Africa.
Contemp Clin Trials
PUBLISHED: 08-05-2010
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South Africa has the third highest annual number of new tuberculosis (TB) cases globally. The resurgence of TB which has particularly affected gold miners in South Africa, is attributed to occupational risk factors for TB including silica dust exposure and high HIV prevalence. Isoniazid preventive therapy (IPT) is recommended for individuals at high risk to prevent both HIV-related TB and silicotuberculosis, but global uptake has been poor. We describe the design of a cluster randomised study, "Thibela TB", which compares routine IPT targeted to those identified as at higher risk of TB (due to HIV infection or silicosis) against a "community-wide" approach in which IPT is offered to all employees. The trial is registered with the Current Controlled Trials: Registration number ISRCTN63327174.
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Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study.
BMC Public Health
PUBLISHED: 07-23-2010
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Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa.
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Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study.
BMC Public Health
PUBLISHED: 07-22-2010
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Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence.
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Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources.
Lancet Infect Dis
PUBLISHED: 07-09-2010
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Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy.
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Reducing mortality with cotrimoxazole preventive therapy at initiation of antiretroviral therapy in South Africa.
AIDS
PUBLISHED: 05-25-2010
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To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy (cART).
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Scale-up of services and research priorities for diagnosis, management, and control of tuberculosis: a call to action.
Lancet
PUBLISHED: 05-18-2010
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The Millennium Development Goal target for tuberculosis control is to halt the spread of tuberculosis by 2015, and begin to reverse the worldwide incidence. After the introduction of standard control practices in 1995, 36 million people were cured and about 6 million deaths were averted. However, substantial scientific advances and innovative solutions are urgently needed together with creative new strategies. Strong international and national political commitment is essential. Urgent action is needed by national governments to fund their own programmes, and for the G8 countries and other donor governments and organisations to support governmental and non-governmental efforts. To foster the global need for urgent action to control the tuberculosis epidemic, The Lancet, in collaboration with the Stop TB Partnership, WHO, Global Fund to Fight AIDS, Tuberculosis and Malaria, and the experts participating in this Series, is launching The Lancet TB Observatory, which will assess and monitor progress in tuberculosis control and research, assess domestic and global financing, regularly disseminate information, and advocate for intensified efforts with stakeholders at all levels.
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Provider-initiated symptom screening for tuberculosis in Zimbabwe: diagnostic value and the effect of HIV status.
Bull. World Health Organ.
PUBLISHED: 04-30-2010
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To assess the diagnostic value of provider-initiated symptom screening for tuberculosis (TB) and how HIV status affects it.
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Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting.
AIDS
PUBLISHED: 03-20-2010
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Despite World Health Organization recommendations, concerns about promoting resistance have impeded implementation of isoniazid preventive therapy (IPT) for tuberculosis (TB). We describe characteristics of TB in individuals previously exposed to IPT as part of Thibela TB, a cluster-randomized trial of community-wide IPT in gold miners in South Africa.
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Advances in immunotherapy for tuberculosis treatment.
Clin. Chest Med.
PUBLISHED: 11-21-2009
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Immunotherapies have the potential to improve the outcome in all patients with tuberculosis (TB) including those with multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB. Immunotherapy for TB may shorten duration of treatment and reduce pathology in individuals cured by chemotherapy, potentially preventing recurrence. Currently none of the available candidate agents have proof of efficacy for use in MDR-TB or XDR-TB. Further development and evaluation of existing immunotherapeutic agents is required to identify an effective agent that can be used adjunctively with chemotherapy to improve treatment outcomes for drug-susceptible TB, MDR-TB, and XDR-TB. With a range of potential immunotherapeutics, some of which have been produced to good manufacturing practice (GMP) standards and are registered for other indications in humans, the immunotherapy option should no longer be ignored.
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Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa.
Clin. Infect. Dis.
PUBLISHED: 11-17-2009
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Episodes of viremia are common in African antiretroviral therapy (ART) programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination ART (cART) in South Africa.
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Incidence of tuberculosis and HIV and progression of silicosis and lung function impairment among former Basotho gold miners.
Am. J. Ind. Med.
PUBLISHED: 11-03-2009
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Pulmonary tuberculosis and HIV incidence, mortality, and the progression of silicosis and lung function impairment are described over a 1-year period in migrant ex-gold miners from Lesotho.
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HIV infection does not affect active case finding of tuberculosis in South African gold miners.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-10-2009
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Gold miners in South Africa undergo annual radiological screening for tuberculosis in an occupational health center of a gold mining company, but the optimal screening algorithm is unclear.
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Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T polymorphism on efavirenz concentrations in adults in South Africa.
Antivir. Ther. (Lond.)
PUBLISHED: 08-26-2009
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Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 (CYP2B6), which metabolizes efavirenz. The CYP2B6 516G>T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than in Caucasians. We explored the effect of rifampicin-based antitubercular therapy and the 516G>T polymorphism on efavirenz concentrations in HIV-infected patients in South Africa.
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Achieving the health Millennium Development Goals for South Africa: challenges and priorities.
Lancet
PUBLISHED: 08-24-2009
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15 years after liberation from apartheid, South Africans are facing new challenges for which the highest calibre of leadership, vision, and commitment is needed. The effect of the unprecedented HIV/AIDS epidemic has been immense. Substantial increases in mortality and morbidity are threatening to overwhelm the health system and undermine the potential of South Africa to attain the Millennium Development Goals (MDGs). However The Lancets Series on South Africa has identified several examples of leadership and innovation that point towards a different future scenario. We discuss the type of vision, leadership, and priority actions needed to achieve such a change. We still have time to change the health trajectory of the country, and even meet the MDGs. The South African Government, installed in April, 2009, has the mandate and potential to address the public health emergencies facing the country--will they do so or will another opportunity and many more lives be lost?
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HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response.
Lancet
PUBLISHED: 08-24-2009
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One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0.7% of the worlds population, had 17% of the global burden of HIV infection, and one of the worlds worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Governments response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.
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Epidemiology of HIV-associated tuberculosis.
Curr Opin HIV AIDS
PUBLISHED: 06-18-2009
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We review literature concerning the epidemiology of HIV-associated tuberculosis (HIV-TB), focusing on articles published between 2007 and 2008.
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The diarylquinoline TMC207 for multidrug-resistant tuberculosis.
N. Engl. J. Med.
PUBLISHED: 06-05-2009
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The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis.
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HIV suppression with stavudine 30 mg versus 40 mg in adults over 60 kg on antiretroviral therapy in South Africa.
AIDS
PUBLISHED: 06-04-2009
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In 2007, the WHO recommended a maximum stavudine dose of 30 mg. We compared virologic suppression among patients weighing more than 60 kg and receiving stavudine 30 mg (n = 110) versus 40 mg (n = 508) in community HIV clinics in South Africa, before and after guidelines changed. At 6 months, HIV RNA less than 400 copies/ml was achieved in 79% and 81% receiving 30 and 40 mg stavudine, respectively (chi2, P = 0.6). In regression modeling, including baseline HIV RNA and nonnucleoside reverse transcriptase inhibitor agent, stavudine dose remained unassociated with suppression.
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"Proof-of-concept" evaluation of an automated sputum smear microscopy system for tuberculosis diagnosis.
PLoS ONE
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"TBDx" is an innovative smear microscopy system that automatically loads slides onto a microscope, focuses and digitally captures images and then classifies smears as positive or negative using computerised algorithms.
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Performance characteristics of the Cepheid Xpert MTB/RIF test in a tuberculosis prevalence survey.
PLoS ONE
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Xpert MTB/RIF ("Xpert") is a molecular test for detection of Mycobacterium tuberculosis (MTB) in sputum. Performance characteristics have been established for its use during passive tuberculosis (TB) case detection in symptomatic TB suspects, but Xpert performance has not been assessed in other settings. Objectives were to determine Xpert performance and costs in the context of a TB prevalence survey.
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Outcomes following virological failure and predictors of switching to second-line antiretroviral therapy in a South African treatment program.
J. Acquir. Immune Defic. Syndr.
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Without resistance tests, deciding which patients with virological failure should switch to second-line antiretroviral therapy (ART) is difficult. The factors influencing this decision are poorly understood. We assess predictors of switching regimens after virological failure.
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Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.
PLoS ONE
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As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART.
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Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control.
J. Acquir. Immune Defic. Syndr.
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Initiation of antiretroviral therapy (ART) and the 3Is are strategies to prevent HIV-associated tuberculosis (TB). We describe factors associated with undiagnosed TB among HIV-infected patients attending an HIV clinic in South Africa and discuss implications for the 3 Is.
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Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women.
PLoS ONE
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HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy.
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A novel HIV treatment model using private practitioners in South Africa.
Sex Transm Infect
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The extent of the HIV epidemic in South Africa may render the public sector capacity inadequate to manage all patients requiring antiretroviral treatment (ART). Private practitioners are an underutilised resource.
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Genotype MTBDRplus for direct detection of Mycobacterium tuberculosis and drug resistance in strains from gold miners in South Africa.
J. Clin. Microbiol.
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GenoType MTBDRplus is a molecular assay for detection of Mycobacterium tuberculosis and drug resistance. Assay performance as applied directly to consecutive unselected sputum samples has not been established. The objective of this study was to determine the accuracy of the MTBDRplus test for direct detection of M. tuberculosis (in sputum) and for drug resistance in consecutively submitted sputum samples. In this cross-sectional study in South Africa, one sputum specimen from each person suspected of having pulmonary tuberculosis was tested by smear microscopy, direct MTBDRplus, and Mycobacterial Growth Indicator Tube (MGIT) culture with MGIT drug susceptibility testing. MGIT results were the reference standard. We tested 2,510 sputum samples, and 529 (21.1%) were positive for M. tuberculosis by MGIT. Direct MTBDRplus identified M. tuberculosis in 256 of 529 specimens (sensitivity, 48.4%; 95% confidence interval [CI], 44.1, 52.7). The sensitivity of MTBDRplus for M. tuberculosis detection by sputum smear status was as follows: smear negative, 13.7% (95% CI, 9.8, 18.4); smear scanty, 46.2% (95% CI, 19.2, 74.9); smear 1+, 69.1% (95% CI, 55.2, 80.9); smear 2+, 86.3% (95% CI, 73.7, 94.3); smear 3+, 89.8% (95% CI, 83.7, 94.2). Direct MTBDRplus testing was negative for 1,594/1,612 sputum samples that were culture negative for M. tuberculosis (specificity, 98.9%; 95% CI, 98.2, 99.3). For specimens positive for M. tuberculosis by MTBDRplus, this assays sensitivity and specificity for rifampin resistance were 85.7% (95% CI, 57.2, 98.2) and 96.6% (95% CI, 93.2, 98.6) and for isoniazid resistance they were 62.1% (95% CI, 42.3, 79.3) and 97.9% (95% CI, 94.8, 99.4). For sputum testing, the sensitivity of MTBDRplus is directly related to the specimens bacillary burden. Our results support recommendations that the MTBDRplus test not be used for direct testing of smear-negative or paucibacillary sputum samples.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.