TB and HIV Therapeutics: Pharmacology Research Priorities.
Ontology highlight
ABSTRACT:
SUBMITTER: Dooley KE
PROVIDER: S-EPMC3398575 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
TB and HIV Therapeutics: Pharmacology Research Priorities.
Dooley Kelly E KE Kim Peter S PS Williams Sharon D SD Hafner Richard R
AIDS research and treatment 20120705
An unprecedented number of investigational drugs are in the development pipeline for the treatment of tuberculosis. Among patients with tuberculosis, co-infection with HIV is common, and concurrent treatment of tuberculosis and HIV is now the standard of care. To ensure that combinations of anti-tuberculosis drugs and antiretrovirals are safe and are tested at doses most likely to be effective, selected pharmacokinetic studies based on knowledge of their metabolic pathways and their capacity to ...[more]
Similar Datasets
Project description:To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight the existing gaps and priority areas for future research.A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population.We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps.Adolescent interventions fall into 3 main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, whereas promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group.Adolescents have unique needs with respect to HIV prevention, and, thus, interventions should be designed to most effectively reach out to this population with information and services that will be relevant to them.
| S-EPMC3746811 | biostudies-other
Project description:BackgroundThere are few published reports of research training needs assessments and research training programs. In an effort to expand this nascent field of study and to bridge the gap between research and practice, we sought to systematically assess the research training needs of health care professionals working at Peruvian governmental institutions leading HIV and tuberculosis (TB) control and among senior stakeholders in the field.MethodsSix institutional workshops were conducted with the participation of 161 mid-level health professionals from agencies involved in national HIV and TB control. At each workshop informants completed a structured questionnaire and participated in small and large group discussions. Additional data and institutional commitment was obtained through in-depth interviews from 32 senior managers and researchers from the Ministry of Health, academia and NGOs.ResultsParticipants exhibited an overwhelming receptivity for additional research training, observing a gap between current levels of research training and their perceived importance. Specialized skills in obtaining funding, developing research protocols, particularly in operational, behavioral and prevention research were considered in greatest need. Beyond research training, participants identified broader social, economic and political factors as influential in infectious disease control.ConclusionsThe needs assessment suggests that future training should focus on operational research techniques, rather than on clinical skill building or program implementation only. Strengthening health systems not only requires additional research training, but also adequate financial resources to implement research findings.
| S-EPMC2955044 | biostudies-literature
Project description:Oral sotalol, used in adults for sinus rhythm control, is initiated at 80 mg b.i.d. and titrated to a maximum safe dose. The US Food and Drug Administration recommends monitoring the corrected QT interval (QTc ) for at least 3 days, until steady-state exposure of the drug is reached, before patient discharge, which can significantly impact the total cost of treatment. The objectives of this research were to design an accelerated intravenous sotalol loading and maintenance therapy that will reduce the hospital length of stay and to also evaluate the pharmacoeconomic impact in a hospital setting. Pharmacokinetic simulations of sotalol plasma concentrations vs. times profiles were performed to determine the optimal intravenous/oral transition regimen. A cost minimization analysis from the health sector perspective was conducted to assess the cost savings for these proposed accelerated regimens. For a chosen target dose of 120 mg b.i.d., two infusions of 40 mg over 1 hour and 20 mg over 0.5 hour, each followed up by an evaluation of QTc , can be administered followed immediately by the target oral maintenance dose of 120 mg at the end of the second infusion. Consequently, steady-state exposure and, therefore, steady-state QTc are obtained on the first day of therapy, facilitating an earlier hospital discharge. Two and 1-day mean total cost of -$3,123 (95% confidence interval (CI), -$3,640, -$2,607) -$4,820 (95% CI, -$5,352, -$4,288) were observed for this strategy, respectively. We are proposing an intravenous to oral transition strategy for sotalol that has the potential to significantly reduce cost and increase patient convenience.
| S-EPMC6853149 | biostudies-literature
Project description:The multifunctional protein - tissue inhibitor of metalloproteinases-1 (TIMP-1) - has been associated with poor prognosis in several types of cancers including glioblastomas. Glioblastomas are the most common and malignant primary brain tumor known for being highly invasive and resistant to therapy. New treatment strategies are continuously being explored and currently vascular endothelial growth factor (VEGF) inhibitors administered in combination with Irinotecan is the most promising second line treatment. TIMP-1 has been associated with decreased response to chemotherapy in breast and colorectal cancer and especially the family of topoisomerase (TOP) inhibitors, such as Irinotecan, has been suggested to be affected by TIMP-1. In the present study, we investigated whether a high TIMP-1 expression in glioblastoma cells played a role in TOP inhibitor resistance. We established two TIMP-1 over-expressing cell lines and evaluated the sensitivity towards the TOP1 inhibitor SN-38 and the TOP2 inhibitor Epirubicin using a viability and a cytotoxicity assay. In addition, we investigated the invasive features of the cells in a brain slice culture model as well as in an orthotopic xenograft model. The results showed that TIMP-1 over-expressing U87MG cell line sub-clones were significantly more resistant than the controls when exposed to SN-38 and Epirubicin. The same tendency was seen for the TIMP-1 over-expressing A172 sub-clones. No significant differences in invasion patterns were observed for TIMP-1 over-expressing sub-clones when compared to controls. In conclusion, the present study suggests that TIMP-1 over-expression reduces the effect of TOP inhibitors in the glioblastoma cell line U87MG. There was no significant effect of TIMP-1 over-expression on tumor cell invasion. The association found between TIMP-1 cellular levels and the effect of TOP inhibitors needs to be validated in clinical patient material.
| S-EPMC3823891 | biostudies-literature
Project description:IntroductionDegenerative cervical myelopathy (DCM) is a progressive neurodegenerative disorder. DCM is common (estimated prevalence, 2% of adults) and significantly impacts quality of life. The AO Spine RECODE-DCM (Research Objectives and Common Data Elements in DCM) project has recently established the top research priorities for DCM. This article examines the extent to which existing research activity aligns with the established research priorities.MethodsA systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and August 08, 2020 were considered eligible. Extracted data for each study included authors, journal, year of publication, location, sample size and study design. Each study was then analysed for alignment to the established research priorities.ResultsIn total, 2261 papers with a total of 1,323,979 patients were included. Japan published more papers (625) than any other country. Moreover, 2005 (89%) of 2261 papers were aligned to at least one research priority. The alignment of papers to the different research priorities was unequal, with 1060 papers on the most researched priority alone (#15, predictors of outcome after treatment), but only 64 total papers on the least-researched 10 priorities. The comparative growth of research in the different priorities was also unequal, with some priorities growing and others plateauing over the past 5 years.DiscussionResearch activity in DCM continues to grow, and the focus of this research remains on surgery. The established research priorities therefore represent a new direction for the field.
| S-EPMC8116279 | biostudies-literature
Project description:There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.
| S-EPMC3531820 | biostudies-other
Project description:Microbiome research has increased dramatically in recent years, driven by advances in technology and significant reductions in the cost of analysis. Such research has unlocked a wealth of data, which has yielded tremendous insight into the nature of the microbial communities, including their interactions and effects, both within a host and in an external environment as part of an ecological community. Understanding the role of microbiota, including their dynamic interactions with their hosts and other microbes, can enable the engineering of new diagnostic techniques and interventional strategies that can be used in a diverse spectrum of fields, spanning from ecology and agriculture to medicine and from forensics to exobiology. From June 19-23 in 2017, the NIH and NSF jointly held an Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome. This review is inspired by some of the topics that arose as priority areas from this unique, interactive workshop. The goal of this review is to summarize the Innovation Lab's findings by introducing the reader to emerging challenges, exciting potential, and current directions in microbiome research. The review is broken into five key topic areas: (1) interactions between microbes and the human body, (2) evolution and ecology of microbes, including the role played by the environment and microbe-microbe interactions, (3) analytical and mathematical methods currently used in microbiome research, (4) leveraging knowledge of microbial composition and interactions to develop engineering solutions, and (5) interventional approaches and engineered microbiota that may be enabled by selectively altering microbial composition. As such, this review seeks to arm the reader with a broad understanding of the priorities and challenges in microbiome research today and provide inspiration for future investigation and multi-disciplinary collaboration.
| S-EPMC7042322 | biostudies-literature
Project description:OBJECTIVE:To identify research priorities to increase understanding of the pathogenesis, diagnosis, and improved treatment of spasmodic dysphonia. STUDY DESIGN AND SETTING:A multidisciplinary working group was formed that included both scientists and clinicians from multiple disciplines (otolaryngology, neurology, speech pathology, genetics, and neuroscience) to review currently available information on spasmodic dysphonia and to identify research priorities. RESULTS:Operational definitions for spasmodic dysphonia at different levels of certainty were recommended for diagnosis and recommendations made for a multicenter multidisciplinary validation study. CONCLUSIONS:The highest priority is to characterize the disorder and identify risk factors that may contribute to its onset. Future research should compare and contrast spasmodic dysphonia with other forms of focal dystonia. Development of animal models is recommended to explore hypotheses related to pathogenesis. Improved understanding of the pathophysiology of spasmodic dysphonia should provide the basis for developing new treatment options and exploratory clinical trials. SIGNIFICANCE:This document should foster future research to improve the care of patients with this chronic debilitating voice and speech disorder by otolaryngology, neurology, and speech pathology.
| S-EPMC2643054 | biostudies-literature
Project description:The clinical variability in patients with sarcomeric cardiomyopathies is striking: a mutation causes cardiomyopathy in one individual, while the identical mutation is harmless in a family member. Moreover, the clinical phenotype varies ranging from asymmetric hypertrophy to severe dilatation of the heart. Identification of a single phenotype-associated disease mechanism would facilitate the design of targeted treatments for patient groups with different clinical phenotypes. However, evidence from both the clinic and basic knowledge of functional and structural properties of the sarcomere argues against a 'one size fits all' therapy for treatment of one clinical phenotype. Meticulous clinical and basic studies are needed to unravel the initial and progressive changes initiated by sarcomere mutations to better understand why mutations in the same gene can lead to such opposing phenotypes. Ultimately, we need to design an 'integrative physiology' approach to fully realize patient/gene-tailored therapy. Expertise within different research fields (cardiology, genetics, cellular biology, physiology, and pharmacology) must be joined to link longitudinal clinical studies with mechanistic insights obtained from molecular and functional studies in novel cardiac muscle systems. New animal models, which reflect both initial and more advanced stages of sarcomeric cardiomyopathy, will also aid in achieving these goals. Here, we discuss current priorities in clinical and preclinical investigation aimed at increasing our understanding of pathophysiological mechanisms leading from mutation to disease. Such information will provide the basis to improve risk stratification and to develop therapies to prevent/rescue cardiac dysfunction and remodelling caused by sarcomere mutations.
| S-EPMC4375392 | biostudies-literature
Project description:Operational research (OR) is the discipline of using models, either quantitative or qualitative, to aid decision-making in complex implementation problems. The methods of OR have been used in healthcare since the 1950s in diverse areas such as emergency medicine and the interface between acute and community care; hospital performance; scheduling and management of patient home visits; scheduling of patient appointments; and many other complex implementation problems of an operational or logistical nature.To date, there has been limited debate about the role that operational research should take within implementation science. I detail three such roles for OR all grounded in upfront system thinking: structuring implementation problems, prospective evaluation of improvement interventions, and strategic reconfiguration. Case studies from mental health, emergency medicine, and stroke care are used to illustrate each role. I then describe the challenges for applied OR within implementation science at the organisational, interventional, and disciplinary levels. Two key challenges include the difficulty faced in achieving a position of mutual understanding between implementation scientists and research users and a stark lack of evaluation of OR interventions. To address these challenges, I propose a research agenda to evaluate applied OR through the lens of implementation science, the liberation of OR from the specialist research and consultancy environment, and co-design of models with service users. Operational research is a mature discipline that has developed a significant volume of methodology to improve health services. OR offers implementation scientists the opportunity to do more upfront system thinking before committing resources or taking risks. OR has three roles within implementation science: structuring an implementation problem, prospective evaluation of implementation problems, and a tool for strategic reconfiguration of health services. Challenges facing OR as implementation science include limited evidence and evaluation of impact, limited service user involvement, a lack of managerial awareness, effective communication between research users and OR modellers, and availability of healthcare data. To progress the science, a focus is needed in three key areas: evaluation of OR interventions, embedding the knowledge of OR in health services, and educating OR modellers about the aims and benefits of service user involvement.
| S-EPMC4895878 | biostudies-other