Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis.

Xpert MTB/RIF is a rapid test to diagnose tuberculosis (TB) and rifampicin-resistant TB. Cost and affordability will influence its uptake. We assessed the cost, globally and in 36 high-burden countries, of two strategies for diagnosing TB and multidrug-resistant (MDR)-TB: Xpert with follow-on diagnostics, and conventional diagnostics. Costs were compared with funding available for TB care and control, and donor investments in HIV prevention and care. Using Xpert to diagnose MDR-TB would cost US$70-90 million per year globally and be lower cost than conventional diagnostics globally and in all high-burden countries. Diagnosing TB in HIV-positive people using Xpert would also cost US$90-101 million per year and be lower cost than conventional diagnostics globally and in 33 out of 36 high-burden countries. Testing everyone with TB signs and symptoms would cost US$434-468 million per year globally, much more than conventional diagnostics. However, in European countries, Brazil and South Africa, the cost would represent <10% of TB funding. Introducing Xpert to diagnose MDR-TB and to diagnose TB in HIV-positive people is warranted in many countries. Using it to test everyone with TB signs and symptoms is affordable in several middle-income countries, but financial viability in low-income countries requires large increases in TB funding and/or further price reductions

Patient- and provider-level risk factors associated with default from tuberculosis treatment, South Africa, 2002: a case-control study

<p>Abstract</p> <p>Background</p> <p>Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa.</p> <p>Methods</p> <p>We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default.</p> <p>Results</p> <p>The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19).</p> <p>Conclusions</p> <p>Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success.</p

Design Aspects for Rehabilitation Games for MS Patients

ABSTRACT Computer-supported rehabilitation can benefit many groups of patients. However, when designing such a therapy, it is important to take the characteristics of the patient population and the wishes of the therapists involved into account. This paper therefore focuses on the requirements of rehabilitation games for Multiple Sclerosis patients. As we have created a system for rehabilitating Multiple Sclerosis, based on a virtual environment with force feedback, we will discuss how these requirements can be met using the rehabilitation system as an example

Safety and Availability of Clofazimine in the Treatment of Multidrug and Extensively Drug-Resistant Tuberculosis: Analysis of Published Guidance and Meta-Analysis of Cohort Studies

Objectives: Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with anti-mycobacterial activity currently used to treat leprosy. Design: Fixed and random effects meta-analysis of cohort studies and systematic review Setting: Electronic and manual searches were combined. Inclusion criteria: Observational studies on treatment of multidrug- and extremely drug- resistant tuberculosis with clofazimine or a clofazimine-containing regimen, and published guidance and documents relating to cost and availability were eligible. Results: Five observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI: [0.0, 0.6%]), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered. Conclusions: While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for MDR-TB patients.Other Research Uni

T2 FLAIR hyperintensity volume Is associated with cognitive function and quality of life in clinically stable patients with lower grade gliomas

Survival outcomes for patients with lower grade gliomas (LrGG) continue to improve. However, damage caused both by tumor growth and by the consequences of treatment often leads to significantly impaired cognitive function and quality of life (QoL). While neuropsychological testing is not routine, serial clinical MRIs are standard of care for patients with LrGG. Thus, having a greater understanding of MRI indicators of cognitive and QoL impairment risk could be beneficial to patients and clinicians. In this work we sought to test the hypothesis that in clinically stable LrGG patients, T2 FLAIR hyperintensity volumes at the time of cognitive assessment are associated with impairments of cognitive function and QoL and could be used to help identify patients for cognitive and QoL assessments and interventions. We performed anatomical MR imaging, cognitive testing and QoL assessments cross-sectionally in 30 clinically stable grade 2 and 3 glioma patients with subjective cognitive concerns who were 6 or more months post-treatment. Larger post-surgical T2 FLAIR volume at testing was significantly associated with lower cognitive performance, while pre-surgical tumor volume was not. Older patients had lower cognitive performance than younger patients, even after accounting for normal age-related declines in performance. Patients with Astrocytoma, IDH mutant LrGGs were more likely to show lower cognitive performance than patients with Oligodendroglioma, IDH mutant 1p19q co-deleted LrGGs. Previous treatment with combined radiation and chemotherapy was associated with poorer self-reported QoL, including self-reported cognitive function. This study demonstrates the importance of appreciating that LrGG patients may experience impairments in cognitive function and QoL over their disease course, including during periods of otherwise sustained clinical stability. Imaging factors can be helpful in identifying vulnerable patients who would benefit from cognitive assessment and rehabilitation

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Tuberculosis Diagnostics and Biomarkers: Needs, Challenges, Recent Advances, and Opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostic

Translational research for tuberculosis elimination: priorities, challenges, and actions

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035

Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda

Frank Cobelens and colleagues outline key research questions that need to be addressed to maximize the impact of programmatic management of drug-resistant tuberculosis