Challenges of loss to follow-up in tuberculosis research

Background

In studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and reasons for not attending were examined.

Methods

In 160 children who attended and 102 children who did not attend scheduled 2-month follow-up baseline health characteristics, demographic data and risk factors for not attending follow-up were determined. Qualitative interviews were used to understand patient and caretakers reasons for not returning for scheduled follow-up.

Results

Being treated for active TB in the DOTS program (OR: 4.14; 95% CI:1.99–8.62;p-value<0.001) and receiving money for the bus fare (OR:129; 95% CI 16->100;P-value<0.001) were positive predictors for attending follow-up at 2 months, and 21/85(25%) of children not attending scheduled follow-up had died. Interviews revealed that limited financial resources, i.e. lack of money for transportation and poor communication, were related to non-adherence.

Conclusion

Patients lost to follow-up is a potential problem for TB research. Receiving money for transportation to the hospital and communication is crucial for adherence to follow-up conducted at a study facility. Strategies to ensure follow-up should be part of any study protocol.     

Challenges facing drug development for malaria

Malaria is a significant cause of morbidity and mortality in the developing world. Until recently malaria was winning but with increase in funding particularly from philanthropic groups the ability to control malaria is again possible. There are still many challenges to developing the next generations of anti-malarials. This article will briefly discuss the challenges and the advance that are being made.     

Metabolomics for phytomedicine research and drug development

Metabolomics, including both targeted and global metabolite profiling strategies, is fast becoming the approach of choice across a broad range of sciences including systems biology, drug discovery, molecular and cell biology, and other medical and agricultural sciences. New analytical and bioinformatics technologies and techniques are continually being created or optimized, significantly increasing the crossdisciplinary capabilities of this new biology. The metabolomes of medicinal plants are particularly a valuable natural resource for the evidence-based development of new phytotherapeutics and nutraceuticals. Comparative metabolomics platforms are evolving into novel technologies for monitoring disease development, drug metabolism, and chemical toxicology. An efficient multidisciplinary marriage of these emerging metabolomics techniques with agricultural biotechnology will greatly benefit both basic and applied medical research.     

对研发新型结核病疫苗的分析和展望

结核病是公共卫生当前面临的重要问题。由于BCG预防效果不佳,研究和开发新型结核病疫苗显得必须且急迫。新型结核病疫苗的研究开发路径和观念也经历了变迁,当前主流的研发路径有重组BCG或重组结核菌、重组痘病毒或重组腺病毒载体疫苗、蛋白质亚单位或重组融合蛋白质亚单位疫苗三类,它们在疫苗效力前景,抗原选型、配方、剂型,免疫应答,疫苗生产,疫苗质量控制,临床前研究动物试验,临床试验和使用,对结核病公共卫生政策的影响等方面各有优劣。新型结核病疫苗的成功研发,还需要病原学、发病机制、免疫学和疫苗研发科学的进一步努力。     

Multi-target drugs: the trend of drug research and development

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.     

从文献计量看海洋药物研发趋势的变化

本文对Science Citation Index Expanded （SCI-E）以及Medline数据库1998—2007年收录的海洋药物相关文章进行文献讨一量分析,统计了发文量居前10位的国家或地区、研究机构、作者以及他们各自对应文章的总被引频次和平均被引频次等数据,数据库中所收录的文献的附加关键词和主题词分布等,以反映近年来海洋药物研发趋势的变化。     

Challenges,achievements and opportunities in allelopathy research

Abstract

Allelopathy is defined as the suppression of any aspect of growth and/or development of one plant by another through the release of chemical compounds. Although allelopathic interference has been demonstrated many times using in vitro experiments, few studies have clearly demonstrated allelopathy in natural settings. This difficulty reflects the complexity in examining and demonstrating allelopathic interactions under field conditions. In this paper we address a number of issues related to the complexity of allelopathic interference in higher plants: These are: (i) is a demonstrated pattern or zone of inhibition important in documenting allelopathy? (ii) is it ecologically relevant to explain the allelopathic potential of a species based on a single bioactive chemical? (iii) what is the significance of the various modes of allelochemical release from the plant into the environment? (iv) do soil characteristics clearly influence allelopathic activity? (v) is it necessary to exclude other plant interference mechanisms?, and (vi) how can new achievements in allelopathy research aid in solving problems related to relevant ecological issues encountered in research conducted upon natural systems and agroecosystems? A greater knowledge of plant interactions in ecologically relevant environments, as well as the study of biochemical pathways, will enhance our understanding of the role of allelopathy in agricultural and natural settings. In addition, novel findings related to the relevant enzymes and genes involved in production of putative allelochemicals, allelochemical persistence in the rhizosphere, the molecular target sites of allelochemicals in sensitive plant species and the influence of allelochemicals upon other organisms will likely lead to enhanced utilization of natural products for pest management or as pharmaceuticals and nutraceuticals. This review will address these recent findings, as well as the major challenges which continue to influence the outcomes of allelopathy research.     

Challenges in microbial fuel cell development and operation

A microbial fuel cell (MFC) is a device that converts chemical energy into electricity through the catalytic activities of microorganisms. Although there is great potential of MFCs as an alternative energy source, novel wastewater treatment process, and biosensor for oxygen and pollutants, extensive optimization is required to exploit the maximum microbial potential. In this article, the main limiting factors of MFC operation are identified and suggestions are made to improve performance.     

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Rational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s when theoretical knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent.     

Adjuvants in tuberculosis vaccine development

Tuberculosis remains a major public health problem around the world. Because the Mycobacterium bovis Bacilli–Calmette–Guerin (BCG) vaccine fails to protect adults from pulmonary tuberculosis, there is an urgent need for improved vaccine formulations. Unlike BCG, recombinant vaccines purified from bacterial expression vectors, as well as naked DNA, require an additional adjuvant. Recent improvements in our understanding of disease immunopathology, together with advances in biochemical and molecular techniques, have permitted the successful development of promising tuberculosis vaccine delivery and adjuvant combinations for human use. Here, we summarize the current state of adjuvant development and its impact on tuberculosis vaccine progress.     

Pharmacogenetics in drug development

Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insights into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenetics (PGx-the use of genetic information to impact drug choice) has been limited to comparatively simple phenotypes such as plasma drug levels. Progress in genetics technologies has broadened the scope of PGx efficacy and safety studies that can be implemented, impacting on a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to affect both the approach to clinical development and the probability of success--the latter being an important aspect for pharmaceutical companies and for the patients who will benefit from these new medicines.     

Positron emission tomography neuroreceptor imaging as a tool in drug discovery, research and development.

Improved communication and cooperation between research-driven drug companies and academic positron emission tomography (PET) centers, coupled with improvements in PET camera resolution, the availability of small animal PET cameras and a growing list of neuroreceptor-specific PET tracers, have all contributed to a substantial increase in the use and value of PET as a tool in central nervous system drug discovery and development.