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Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis

Lan, Zhiyi ; Ahmad, Nafees ; Baghaei, Parvaneh ; [et al.]

Elsevier BV ; 2020

In: The Lancet Respiratory Medicine Vol. 8, No. 4 ( 2020-04), p. 383-394

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In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 8, No. 4 ( 2020-04), p. 383-394

Type of Medium: Online Resource

ISSN: 2213-2600

URL: Article

DOI: 10.1016/S2213-2600(20)30047-3

Language: English

Publisher: Elsevier BV

Publication Date: 2020

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Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Ahmad, Nafees ; Ahuja, Shama D ; Akkerman, Onno W ; [et al.]

Elsevier BV ; 2018

In: The Lancet Vol. 392, No. 10150 ( 2018-09), p. 821-834

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In: The Lancet, Elsevier BV, Vol. 392, No. 10150 ( 2018-09), p. 821-834

Type of Medium: Online Resource

ISSN: 0140-6736

URL: Article

DOI: 10.1016/S0140-6736(18)31644-1

RVK:

XA 10000

Language: English

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2067452-1

detail.hit.zdb_id: 3306-6

detail.hit.zdb_id: 1476593-7

SSG: 5,21

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Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa

Nelson, Kristin N ; Gandhi, Neel R ; Mathema, Barun ; [et al.]

Oxford University Press (OUP) ; 2020

In: American Journal of Epidemiology Vol. 189, No. 7 ( 2020-07-01), p. 735-745

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In: American Journal of Epidemiology, Oxford University Press (OUP), Vol. 189, No. 7 ( 2020-07-01), p. 735-745

Abstract: Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011–2014. We tested scenarios in which cases were missing at random, missing differentially by clinical characteristics, or missing differentially by transmission (i.e., cases with many links were under- or oversampled). Under the assumption that cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases, and models provided evidence for super-spreading. To our knowledge, this is the first analysis to have assessed support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving super-spreading.

Type of Medium: Online Resource

ISSN: 0002-9262 , 1476-6256

URL: Article

DOI: 10.1093/aje/kwaa028

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

detail.hit.zdb_id: 2030043-8

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Management of active tuberculosis in adults with HIV

Meintjes, Graeme ; Brust, James C M ; Nuttall, James ; [et al.]

Elsevier BV ; 2019

In: The Lancet HIV Vol. 6, No. 7 ( 2019-07), p. e463-e474

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In: The Lancet HIV, Elsevier BV, Vol. 6, No. 7 ( 2019-07), p. e463-e474

Type of Medium: Online Resource

ISSN: 2352-3018

URL: Article

DOI: 10.1016/S2352-3018(19)30154-7

Language: English

Publisher: Elsevier BV

Publication Date: 2019

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TCA cycle remodeling drives proinflammatory signaling in humans with pulmonary tuberculosis

Collins, Jeffrey M. ; Jones, Dean P. ; Sharma, Ashish ; [et al.]

Public Library of Science (PLoS) ; 2021

In: PLOS Pathogens Vol. 17, No. 9 ( 2021-9-24), p. e1009941-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-24), p. e1009941-

Abstract: The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods in plasma high-resolution metabolomics, lipidomics and cytokine profiling from a multicohort study of humans with pulmonary TB disease, we discovered that IL-1β-mediated inflammatory signaling was closely associated with TCA cycle remodeling, characterized by accumulation of the proinflammatory metabolite succinate and decreased concentrations of the anti-inflammatory metabolite itaconate. This inflammatory metabolic response was particularly active in persons with multidrug-resistant (MDR)-TB that received at least 2 months of ineffective treatment and was only reversed after 1 year of appropriate anti-TB chemotherapy. Both succinate and IL-1β were significantly associated with proinflammatory lipid signaling, including increases in the products of phospholipase A2, increased arachidonic acid formation, and metabolism of arachidonic acid to proinflammatory eicosanoids. Together, these results indicate that decreased itaconate and accumulation of succinate and other TCA cycle intermediates is associated with IL-1β-mediated proinflammatory eicosanoid signaling in pulmonary TB disease. These findings support host metabolic remodeling as a key driver of pathologic inflammation in human TB disease.

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1009941

DOI: 10.1371/journal.ppat.1009941.g001

DOI: 10.1371/journal.ppat.1009941.g002

DOI: 10.1371/journal.ppat.1009941.g003

DOI: 10.1371/journal.ppat.1009941.g004

DOI: 10.1371/journal.ppat.1009941.g005

DOI: 10.1371/journal.ppat.1009941.g006

DOI: 10.1371/journal.ppat.1009941.t001

DOI: 10.1371/journal.ppat.1009941.s001

DOI: 10.1371/journal.ppat.1009941.s002

DOI: 10.1371/journal.ppat.1009941.s003

DOI: 10.1371/journal.ppat.1009941.s004

DOI: 10.1371/journal.ppat.1009941.s005

DOI: 10.1371/journal.ppat.1009941.s006

DOI: 10.1371/journal.ppat.1009941.s007

DOI: 10.1371/journal.ppat.1009941.s008

DOI: 10.1371/journal.ppat.1009941.s009

DOI: 10.1371/journal.ppat.1009941.s010

DOI: 10.1371/journal.ppat.1009941.s011

DOI: 10.1371/journal.ppat.1009941.s012

DOI: 10.1371/journal.ppat.1009941.s013

DOI: 10.1371/journal.ppat.1009941.s014

DOI: 10.1371/journal.ppat.1009941.r001

DOI: 10.1371/journal.ppat.1009941.r002

DOI: 10.1371/journal.ppat.1009941.r003

DOI: 10.1371/journal.ppat.1009941.r004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2021

detail.hit.zdb_id: 2205412-1

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Social Mixing and Clinical Features Linked With Transmission in a Network of Extensively Drug-resistant Tuberculosis Cases in KwaZulu-Natal, South Africa

Nelson, Kristin N ; Jenness, Samuel M ; Mathema, Barun ; [et al.]

Oxford University Press (OUP) ; 2020

In: Clinical Infectious Diseases Vol. 70, No. 11 ( 2020-05-23), p. 2396-2402

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 70, No. 11 ( 2020-05-23), p. 2396-2402

Abstract: Tuberculosis (TB) is the leading infectious cause of death globally, and drug-resistant TB strains pose a serious threat to controlling the global TB epidemic. The clinical features, locations, and social factors driving transmission in settings with high incidences of drug-resistant TB are poorly understood. Methods We measured a network of genomic links using Mycobacterium tuberculosis whole-genome sequences. Results Patients with 2–3 months of cough or who spent time in urban locations were more likely to be linked in the network, while patients with sputum smear–positive disease were less likely to be linked than those with smear-negative disease. Associations persisted using different thresholds to define genomic links and irrespective of assumptions about the direction of transmission. Conclusions Identifying factors that lead to many transmissions, including contact with urban areas, can suggest settings instrumental in transmission and indicate optimal locations and groups to target with interventions.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciz636

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

detail.hit.zdb_id: 2002229-3

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Five cases of bacteraemia due to Gordonia species

Brust, James C. M. ; Whittier, Susan ; Scully, Brian E. ; [et al.]

Microbiology Society ; 2009

In: Journal of Medical Microbiology Vol. 58, No. 10 ( 2009-10-01), p. 1376-1378

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In: Journal of Medical Microbiology, Microbiology Society, Vol. 58, No. 10 ( 2009-10-01), p. 1376-1378

Abstract: Gordonia species are aerobic Gram-positive bacilli and a rare cause of human disease. To our knowledge, there are only two cases of human infection with Gordonia sputi reported in the literature. We report five cases of bacteraemia due to Gordonia species at our institution since 2005, including four caused by G. sputi . Three of these cases were likely related to chronic indwelling central venous catheters.

Type of Medium: Online Resource

ISSN: 0022-2615 , 1473-5644

URL: Article

DOI: 10.1099/jmm.0.010272-0

RVK:

XA 55020

Language: English

Publisher: Microbiology Society

Publication Date: 2009

detail.hit.zdb_id: 2083944-3

SSG: 12

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Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment

van Beek, Stijn W ; Tanneau, Lénaïg ; Meintjes, Graeme ; [et al.]

Oxford University Press (OUP) ; 2022

In: Open Forum Infectious Diseases Vol. 9, No. 8 ( 2022-08-02)

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In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 8 ( 2022-08-02)

Abstract: The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment. Methods Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monitoring strategies to identify patients who need to interrupt treatment (QTcF & gt; 500 ms) were explored. Results One hundred seventy patients were included, providing 1131 bedaquiline/M2 plasma concentrations and 1702 QTcF measurements; 2.1% of virtual patients receiving concomitant clofazimine had QTcF & gt; 500 ms at any point during treatment (0.7% without concomitant clofazimine). With monthly monitoring, almost all patients with QTcF & gt; 500 ms were identified by week 12; after week 12, patients were predominantly falsely identified as QTcF & gt; 500 ms due to stochastic measurement error. Following a strategy with monitoring before treatment and at weeks 2, 4, 8, and 12 in simulations with concomitant clofazimine, 93.8% of all patients who should interrupt treatment were identified, and 26.4% of all interruptions were unnecessary (92.1% and 32.2%, respectively, without concomitant clofazimine). Conclusions Our simulations enable an informed decision for a suitable ECG monitoring strategy by weighing the risk of missing patients with QTcF & gt; 500 ms and that of interrupting bedaquiline treatment unnecessarily. We propose ECG monitoring before treatment and at weeks 2, 4, 8, and 12 after starting bedaquiline treatment.

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofac372

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2757767-3

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Clofazimine pharmacokinetics in patients with TB: dosing implications

Abdelwahab, Mahmoud Tareq ; Wasserman, Sean ; Brust, James C M ; [et al.]

Oxford University Press (OUP) ; 2020

In: Journal of Antimicrobial Chemotherapy Vol. 75, No. 11 ( 2020-11-01), p. 3269-3277

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In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 75, No. 11 ( 2020-11-01), p. 3269-3277

Abstract: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. Objectives To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. Patients and methods Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. Plasma concentrations were measured by LC-MS/MS and interpreted with non-linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25 mg/L. Results We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5 L/h and peripheral volume 10 500 L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a loading dose of 200 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. Conclusions Clofazimine was widely distributed with a long elimination half-life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.

Type of Medium: Online Resource

ISSN: 0305-7453 , 1460-2091

URL: Article

DOI: 10.1093/jac/dkaa310

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

detail.hit.zdb_id: 1467478-6

SSG: 15,3

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Polymorphisms in the vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa

Magee, Matthew J. ; Sun, Yan V. ; Brust, James C. M. ; [et al.]

Public Library of Science (PLoS) ; 2017

In: PLOS ONE Vol. 12, No. 7 ( 2017-7-10), p. e0180916-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 12, No. 7 ( 2017-7-10), p. e0180916-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0180916

DOI: 10.1371/journal.pone.0180916.g001

DOI: 10.1371/journal.pone.0180916.t001

DOI: 10.1371/journal.pone.0180916.t002

DOI: 10.1371/journal.pone.0180916.t003

DOI: 10.1371/journal.pone.0180916.s001

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2017

detail.hit.zdb_id: 2267670-3

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