Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal. Newer agents targeting the pathogenic mechanisms underlying SSc-ILD, including fibrotic and inflammatory pathways, lymphocytes, cell-cell and cell-extracellular membrane interactions, hold promise for better treatment outcomes, including improved lung function, patient-related outcomes and quality of life. Here we review ongoing trials of established and novel agents that are currently recruiting patients with SSc-ILD

Universal Plant DNA Barcode Loci May Not Work in Complex Groups: A Case Study with Indian Berberis Species

BACKGROUND: The concept of DNA barcoding for species identification has gained considerable momentum in animals because of fairly successful species identification using cytochrome oxidase I (COI). In plants, matK and rbcL have been proposed as standard barcodes. However, barcoding in complex genera is a challenging task. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the species discriminatory power of four reportedly most promising plant DNA barcoding loci (one from nuclear genome--ITS, and three from plastid genome--trnH-psbA, rbcL and matK) in species of Indian Berberis L. (Berberidaceae) and two other genera, Ficus L. (Moraceae) and Gossypium L. (Malvaceae). Berberis species were delineated using morphological characters. These characters resulted in a well resolved species tree. Applying both nucleotide distance and nucleotide character-based approaches, we found that none of the loci, either singly or in combinations, could discriminate the species of Berberis. ITS resolved all the tested species of Ficus and Gossypium and trnH-psbA resolved 82% of the tested species in Ficus. The highly regarded matK and rbcL could not resolve all the species. Finally, we employed amplified fragment length polymorphism test in species of Berberis to determine their relationships. Using ten primer pair combinations in AFLP, the data demonstrated incomplete species resolution. Further, AFLP analysis showed that there was a tendency of the Berberis accessions to cluster according to their geographic origin rather than species affiliation. CONCLUSIONS/SIGNIFICANCE: We reconfirm the earlier reports that the concept of universal barcode in plants may not work in a number of genera. Our results also suggest that the matK and rbcL, recommended as universal barcode loci for plants, may not work in all the genera of land plants. Morphological, geographical and molecular data analyses of Indian species of Berberis suggest probable reticulate evolution and thus barcode markers may not work in this case

Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa.

Guido Bastiaens and colleagues describe barriers to achieving scale-up and appropriate use of rapid diagnostic tests and artemisinin-based combination therapy for malaria in sub-Saharan Africa. Please see later in the article for the Editors' Summary

From fever to anti-malarial: the treatment-seeking process in rural Senegal.

BACKGROUND: Currently less than 15% of children under five with fever receive recommended artemisinin-combination therapy (ACT), far short of the Roll Back Malaria target of 80%. To understand why coverage remains low, it is necessary to examine the treatment pathway from a child getting fever to receiving appropriate treatment and to identify critical blockages. This paper presents the application of such a diagnostic approach to the coverage of prompt and effective treatment of children with fever in rural Senegal. METHODS: A two-stage cluster sample household survey was conducted in August 2008 in Tambacounda, Senegal, to investigate treatment behaviour for children under five with fever in the previous two weeks. The treatment pathway was divided in to five key steps; the proportion of all febrile children reaching each step was calculated. Results were stratified by sector of provider (public, community, and retail). Logistic regression was used to determine predictors of treatment seeking. RESULTS: Overall 61.6% (188) of caretakers sought any advice or treatment and 40.3% (123) sought any treatment promptly within 48 hours. Over 70% of children taken to any provider with fever did not receive an anti-malarial. The proportion of febrile children receiving ACT within 48 hours was 6.2% (19) from any source; inclusion of correct dose and duration reduced this to 1.3%. The proportion of febrile children receiving ACT within 48 hours (not including dose & duration) was 3.0% (9) from a public provider, 3.0% (9) from a community source and 0.3% (1) from the retail sector. Inclusion of confirmed diagnosis within the public sector treatment pathway as per national policy increases the proportion of children receiving appropriate treatment with ACT in this sector from 9.4% (9/96) to an estimated 20.0% (9/45). CONCLUSIONS: Process analysis of the treatment pathway for febrile children must be stratified by sector of treatment-seeking. In Tambacounda, Senegal, interventions are needed to increase prompt care-seeking for fever, improve uptake of rapid diagnostic tests at the public and community levels and increase correct treatment of parasite-positive patients with ACT. Limited impact will be achieved if interventions to improve prompt and effective treatment target only one step in the treatment pathway in any sector

Current challenges in the management of sepsis in ICUs in resource–poor settings and suggestions for the future

Sepsis is a major reason for intensive care unit (ICU) admission, also in resource–poor settings. ICUs in low– and middle–income countries (LMICs) face many challenges that could affect patient outcome. The aim of this review is to describe differences between resource–poor and resource–rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Although many bacterial pathogens causing sepsis in LMICs are similar to those in high–income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Addressing both disease–specific and setting–specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost–effective in LMIC setting, more detailed evaluation at both at a macro– and micro–economy level is necessary. Sepsis management in resource–limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement

Current challenges in the management of sepsis in ICUs in resource–poor settings and suggestions for the future

Sepsis is a major reason for intensive care unit (ICU) admission, also in resource–poor settings. ICUs in low– and middle–income countries (LMICs) face many challenges that could affect patient outcome. The aim of this review is to describe differences between resource–poor and resource–rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Although many bacterial pathogens causing sepsis in LMICs are similar to those in high–income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Addressing both disease–specific and setting–specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost–effective in LMIC setting, more detailed evaluation at both at a macro– and micro–economy level is necessary. Sepsis management in resource–limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement