Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines.

PubMed

Schito, Marco; Migliori, Giovanni Battista; Fletcher, Helen A; McNerney, Ruth; Centis, Rosella; D'Ambrosio, Lia; Bates, Matthew; Kibiki, Gibson; Kapata, Nathan; Corrah, Tumena; Bomanji, Jamshed; Vilaplana, Cris; Johnson, Daniel; Mwaba, Peter; Maeurer, Markus; Zumla, Alimuddin

2015-10-15

Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Advances in animal models of drug addiction.

PubMed

Heidbreder, Christian

2011-01-01

Drug addiction is a syndrome of impaired response inhibition and salience attribution, which involves a complex neurocircuitry underlying drug reinforcement, drug craving, and compulsive drug-seeking and drug-taking behaviors despite adverse consequences. The concept of disease stages with transitions from acute rewarding effects to early- and end-stage addiction has had an important impact on the design of nonclinical animal models. This chapter reviews the main advances in nonclinical paradigms that aim to at model (1) positive and negative reinforcing effects of addictive drugs; (2) relapse to drug-seeking behavior; (3) reconsolidation of drug cue memories, and (4) compulsive/impulsive drug intake. In addition, recent small animal neuroimaging studies and invertebrate models will be briefly discussed (see also Bifone and Gozzi, Animal models of ADHD, 2011). Continuous improvement in modeling drug intake, craving, withdrawal symptoms, relapse, and comorbid psychiatric associations is a necessary step to better understand the etiology of the disease and to ultimately foster the discovery, validation and optimization of new efficacious pharmacotherapeutic approaches. The modeling of specific subprocesses or constructs that address clinically defined criteria will ultimately increase our understanding of the disease as a whole. Future research will have to address the questions of whether some of these constructs can be reliably used as outcome measures to assess the effects of a treatment in clinical settings, whether changes in those measures can be a target of therapeutic efforts, and whether they relate to biological markers of traits such as impulsivity, which contribute to increased drug-seeking and may predict binge-like patterns of drug intake.

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook.

PubMed

Song, Yuanhui; Li, Yihong; Xu, Qien; Liu, Zhe

With the development of nanotechnology, the application of nanomaterials in the field of drug delivery has attracted much attention in the past decades. Mesoporous silica nanoparticles as promising drug nanocarriers have become a new area of interest in recent years due to their unique properties and capabilities to efficiently entrap cargo molecules. This review describes the latest advances on the application of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled release systems that are able to respond to intracellular environmental changes, such as pH, ATP, GSH, enzyme, glucose, and H 2 O 2 . Moreover, drug delivery induced by exogenous stimuli including temperature, light, magnetic field, ultrasound, and electricity is also summarized. These advanced technologies demonstrate current challenges, and provide a bright future for precision diagnosis and treatment.

Advanced systems biology methods in drug discovery and translational biomedicine.

PubMed

Zou, Jun; Zheng, Ming-Wu; Li, Gen; Su, Zhi-Guang

2013-01-01

Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease

PubMed Central

Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

2014-01-01

Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

PubMed

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

Protein Innovations Advance Drug Treatments, Skin Care

NASA Technical Reports Server (NTRS)

2012-01-01

Dan Carter carefully layered the sheets of tracing paper on the light box. On each sheet were renderings of the atomic components of an essential human protein, one whose structure had long been a mystery. With each layer Carter laid down, a never-before-seen image became clearer. Carter joined NASA s Marshall Space Flight Center in 1985 and began exploring processes of protein crystal growth in space. By bouncing intense X-rays off the crystals, researchers can determine the electron densities around the thousands of atoms forming the protein molecules, unveiling their atomic structures. Cultivating crystals of sufficient quality on Earth was problematic; the microgravity conditions of space were far more accommodating. At the time, only a few hundred protein structures had been mapped, and the methods were time consuming and tedious. Carter hoped his work would help reveal the structure of human serum albumin, a major protein in the human circulatory system responsible for ferrying numerous small molecules in the blood. More was at stake than scientific curiosity. Albumin has a high affinity for most of the world s pharmaceuticals, Carter explains, and its interaction with drugs can change their safety and efficacy. When a medication enters the bloodstream a cancer chemotherapy drug, for example a majority of it can bind with albumin, leaving only a small percentage active for treatment. How a drug interacts with albumin can influence considerations like the necessary effective dosage, playing a significant role in the design and application of therapeutic measures. In spite of numerous difficulties, including having no access to microgravity following the 1986 Space Shuttle Challenger disaster, the image Carter had hoped to see was finally clarifying. In 1988, his lab had acquired specialized X-ray and detection equipment a tipping point. Carter and his colleagues began to piece together albumin s portrait, the formation of its electron densities coalescing on

Update on Nanotechnology-based Drug Delivery Systems in Cancer Treatment.

PubMed

Ho, Benjamin N; Pfeffer, Claire M; Singh, Amareshwar T K

2017-11-01

The emerging field of nanotechnology meets the demands for innovative approaches in the diagnosis and treatment of cancer. The nanoparticles are biocompatible and biodegradable and are made of a core, a particle that acts as a carrier, and one or more functional groups on the core which target specific sites. Nanotech in drug delivery includes nanodisks, High Density Lipoprotein nanostructures, liposomes, and gold nanoparticles. The fundamental advantages of nanoparticles are: improved delivery of water-insoluble drugs, targeted delivery, co-delivery of two or more drugs for combination therapy, and visualization of the drug delivery site by combining imaging system and a therapeutic drug. One of the potential applications of nanotechnology is in the treatment of cancer. Conventional methods for cancer treatments have included chemotherapy, surgery, or radiation. Early recognition and treatment of cancer with these approaches is still challenging. Innovative technologies are needed to overcome multidrug resistance, and increase drug localization and efficacy. Application of nanotechnology to cancer biology has brought in a new hope for developing treatment strategies on cancer. In this study, we present a review on the recent advances in nanotechnology-based approaches in cancer treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Recent advancements in drug treatment of obesity.

PubMed

Carter, Rebeca; Mouralidarane, Angelina; Ray, Shuvra; Soeda, Junpei; Oben, Jude

2012-10-01

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

PubMed Central

Song, Yuanhui; Li, Yihong; Xu, Qien; Liu, Zhe

2017-01-01

With the development of nanotechnology, the application of nanomaterials in the field of drug delivery has attracted much attention in the past decades. Mesoporous silica nanoparticles as promising drug nanocarriers have become a new area of interest in recent years due to their unique properties and capabilities to efficiently entrap cargo molecules. This review describes the latest advances on the application of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled release systems that are able to respond to intracellular environmental changes, such as pH, ATP, GSH, enzyme, glucose, and H2O2. Moreover, drug delivery induced by exogenous stimuli including temperature, light, magnetic field, ultrasound, and electricity is also summarized. These advanced technologies demonstrate current challenges, and provide a bright future for precision diagnosis and treatment. PMID:28053526

Bevacizumab Treatment for Advanced Breast Cancer

PubMed Central

Guarneri, Valentina; Icli, Fikri; Johnston, Stephen; Khayat, David; Loibl, Sibylle; Martin, Miguel; Zielinski, Christoph; Conte, PierFranco; Hortobagyi, Gabriel N.

2011-01-01

Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured. PMID:21976315

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

PubMed

Burke, Erin E; Zager, Jonathan S

2018-04-01

Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

Advances in bioresponsive closed-loop drug delivery systems.

PubMed

Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

2017-11-27

Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug treatment on demand--not.

PubMed

Wenger, L D; Rosenbaum, M

1994-01-01

Drug treatment on demand, appropriate and affordable drug treatment for injection drug users who are "ready" to enter a program, is a humane approach to drug treatment services and an important mechanism to halt the spread of HIV. However, drug treatment on demand is not a reality in the United States. In fact, due to funding cuts at federal, state, and local levels, entry into drug treatment programs has become increasingly more difficult over the past decade. In a NIDA-funded ethnographic study of methadone maintenance, i.v. drug use and AIDS, 70 heroin addicts who were out of treatment and actively seeking methadone maintenance were interviewed. In life-history interviews, the drug users described barriers to treatment, waiting-list experiences, and the impact of these experiences on their drug use, drug-using behavior, and emotional well-being. Respondents used many mechanisms to cope with the lack of availability of drug treatment slots, some of which have increased their risk of exposure to and spread of HIV. These findings indicate the need for an increase in the availability of subsidized methadone maintenance treatment slots "on demand" if individuals are to decrease their drug use and their high-risk behaviors. Drug treatment on demand is more than politically correct rhetoric. It is a necessary ingredient in reducing the harm caused by the use of illegal drugs.

Advanced biotherapy for the treatment of sulfur mustard poisoning.

PubMed

Sun, Mingxue; Yang, Yuyan; Meng, Wenqi; Xu, Qingqiang; Lin, Fengwu; Chen, Yongchun; Zhao, Jie; Xiao, Kai

2018-04-25

Sulfur mustard (SM), a bifunctional alkylating agent, can react with a variety of biochemical molecules (DNA, RNA, proteins and other cell components) to cause a series of serious health issues or even death. Although a plethora of research has been done, the pathogenesis of SM poisoning has yet to be fully understood due to its high complexity. As a consequence, a specific antidote has not yet been developed and the treatment of SM poisoning remains a medical challenge. In recent years, various biological products and cell transplantation in the treatment of SM poisoning offered a significant clinical treatment progress. By highlighting these and other research studies, we hereby summarize the progress in this field in an effort to provide useful information on the clinical treatment of SM poisoning. This review summarizes the major advances of SM poisoning therapy by means of biological products (peptide and protein drugs, polysaccharides drugs, nucleic acid drugs, etc.), and cell transplantation (e.g., bone marrow, limbal stem cells, mesenchymal stem cells), as well as other relevant biotherapeutic approaches. We searched the database PubMed for published domestic and international articles using web based resources for information on histological, immunochemical, ultrastructural, and treatment features of SM-induced manifestations in both animal models and human tissues. To this end, we applied keywords containing mustard gas, chemical warfare, SM, eye, lung and skin. Our review provides a comprehensive understanding of the advances of available biotherapies in SM poisoning, and its potential for the treatment of SM-induced injuries. Potentially, our review will provide new insights for future research studies in this field. Copyright © 2018. Published by Elsevier B.V.

Advancing Drug Discovery through Enhanced Free Energy Calculations.

PubMed

Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A

2017-07-18

A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates

The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer.

PubMed

Soekmadji, Carolina; Nelson, Colleen C

2015-01-01

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Drug-Induced Liver Injury: Advances in Mechanistic Understanding that will Inform Risk Management

PubMed Central

Mosedale, Merrie; Watkins, Paul B.

2016-01-01

Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie most hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis. However, in some cases, hepatocyte stress promotes an immune response that results in clinically important idiosyncratic DILI. This review discusses recent advances in our understanding of the pathogenesis of both intrinsic and idiosyncratic DILI as well as emerging tools and techniques that will likely improve DILI risk identification and management. PMID:27861792

New Targeted Treatment May Slow Disease in Patients with Advanced GIST

Cancer.gov

A new oral drug, regorafenib (Stivarga®), may delay the progression of advanced gastrointestinal stromal tumors (GIST) that are resistant to treatment, according to results from an international clinical trial published November 22, 2012, in The Lancet.

Comparative trial of endocrine versus cytotoxic treatment in advanced breast cancer.

PubMed Central

Priestman, T; Baum, M; Jones, V; Forbes, J

1977-01-01

Ninety-two women with advanced breast cancer were allocated at random to receive either cytotoxic or endocrine treatment. Out of 45 women included in the cytotoxic treatment group, 22 (49%) achieved complete or partial remission of their disease, whereas of the 47 included in the endocrine treatment group, only 10 (21%) achieved such remission. Significantly longer survival times in the cytotoxic treatment group were most apparent among premenopausal women, 75% of such patients responding to cytotoxic drugs (median survival 46 weeks) compared with only 11% benefiting from ovarian ablation (median survival 12 weeks). In postmenopausal women with predominantly soft-tissue disease, however, additive hormonal treatment with tamoxifen produced remission rates and survival times equivalent to those produced by cytotoxic drugs. PMID:324570

A network meta-analysis on the efficacy of sixteen targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer

PubMed Central

Ba-Sang, Dan-Zeng; Long, Zi-Wen; Teng, Hao; Zhao, Xu-Peng; Qiu, Jian; Li, Ming-Shan

2016-01-01

Objective A network meta-analysis was conducted comparing the short-term efficacies of 16 targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer (CRC). Results Twenty-seven RCTs were ultimately incorporated into this network meta-analysis. Compared with chemotherapy alone, bevacizumab + chemotherapy, panitumumab + chemotherapy and conatumumab + chemotherapy had higher PR rate. Bevacizumab + chemotherapy, cetuximab + chemotherapy, panitumumab + chemotherapy, trebananib + chemotherapy and conatumumab + chemotherapy had higher ORR rate in comparison to chemotherapy alone. Furthermore, bevacizumab + chemotherapy had higher DCR rate than chemotherapy alone. The results of our cluster analysis showed that chemotherapy combined with bevacizumab, cetuximab, panitumumab, conatumumab, ganitumab, or brivanib + cetuximab had better efficacies for the treatment of advanced/metastatic CRC in comparison to chemotherapy alone. Materials and Methods Electronic databases were comprehensively searched for potential and related randomized controlled trials (RCTs). Direct and indirect evidence were incorporated for evaluation of stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR) and overall response ratio (ORR) by calculating odds ratio (OR) and 95% confidence intervals (CI), and using the surface under the cumulative ranking curve (SUCRA). Conclusions These results indicated that bevacizumab + chemotherapy, panitumumab + chemotherapy, conatumumab + chemotherapy and brivanib + cetuximab + chemotherapy may have better efficacies for the treatment of advanced/metastatic CRC. PMID:27806321

Chinese Herbal Medicine for the Treatment of Drug Addiction.

PubMed

Zhu, Weili; Zhang, Yinan; Huang, Yingjie; Lu, Lin

2017-01-01

This chapter summarizes recent developments in preclinical and clinical research on Chinese herbal medicines and their neurochemical mechanism of action for the treatment of drug addiction. We searched Chinese and English scientific literature and selected several kinds of Chinese herbal medicines that have beneficial effects on drug addiction. Ginseng (Renshen) may be clinically useful for the prevention of opioid abuse and dependence. Rhizoma Corydalis (Yanhusuo) may be used to prevent relapse to chronic drug dependence. Alkaloids of Uncaria rhynchophylla (Gouteng) appear to have positive effects on methamphetamine and ketamine addiction. Both Salvia miltiorrhiza (Danshen) and Radix Pueraiae (Gegen) have beneficial inhibitory effects on alcohol intake. Sinomenine has been shown to have preventive and curative effects on opioid dependence. l-Stepholidine, an alkaloid extract of the Chinese herb Stephania intermedia (Rulan), attenuated the acquisition, maintenance, and reacquisition of morphine-induced conditioned place preference and antagonized the heroin-induced reinstatement of heroin seeking. Traditional Chinese herbal medicines may be used to complement current treatments for drug addiction, including withdrawal and relapse. As the molecular mechanisms of action of traditional Chinese herbal medicines are elucidated, further advances in their use for the treatment of drug addiction are promising. © 2017 Elsevier Inc. All rights reserved.

Emerging drug treatments for solid tumours.

PubMed

Schellens, J H; Pronk, L C; Verweij, J

1996-01-01

A number of novel anticancer agents have emerged during the past few decades, which show high activity in preclinical tumour models and promising activity in early trials in patients with solid tumours. Most of the agents have novel and unique mechanisms of action, and show activity against a variety of malignancies, including tumours which are notoriously resistant to systemic treatment. Recently, our understanding of the molecular basis of cancer has increased considerably. This is reflected in the development of agents that are directed at well defined molecular targets, such as the mitotic tubulin/microtubuli system (taxoids), nuclear enzymes (topoisomerase I inhibitors) and cell signal transduction pathways (protein kinase C inhibitors). In addition, significant advances have been made in our understanding of mechanisms of toxicity, especially of cisplatin. This has resulted in the development of agents modulating cisplatin toxicity, among which amifostine (WR-2721) is one of the most promising. The outlined emerging drug therapies with novel anticancer agents and treatment modalities will, it is hoped, result in increased response rates of advanced tumours, longer disease-free and total survival and better palliative care.

In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

PubMed

Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

2014-08-01

The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI < 1), additive (CI ~ 1), and predominantly antagonistic (CI > 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI < 1) at higher growth inhibition levels. Our in vitro data warrant further investigation and may provide the basis for nilotinib-supplemented conditioning regimens for allo-SCT in advanced-phase CML.

PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

PubMed Central

Das, Sreemanti; Khuda-Bukhsh, Anisur Rahman

2016-01-01

Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review. PMID:27934796

Advances in the treatment of gastric cancer.

PubMed

Ilson, David H

2017-11-01

To review recent studies in esophagogastric cancer. Positive emission tomography (PET) scan in follow-up after curative treatment of esophagogastric cancer did not lead to improved survival. In the preoperative treatment of esophagogastric cancer, the addition of the antivascular endothelial growth factor agent bevacizumab to perioperative chemotherapy with combination epirubicin, cisplatinum, and 5-fluorouracil (5-FU; ECF) failed to improve survival compared with chemotherapy alone. In a head-to-head comparison of preoperative chemotherapy for locally advanced gastric and esophagogastric adenocarcinoma, FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved overall survival compared with ECF. Assessing response to induction chemotherapy prior to combined preoperative chemoradiotherapy in PET nonresponding patients allowed a change in chemotherapy during subsequent radiotherapy with improved rates of pathologic complete response. In human epidermal growth factor receptor-2-positive advanced esophagogastric adenocarcinoma, second-line treatment with the chemotherapy/trastuzumab drug conjugate emtansine/trastuzumab failed to improve response or overall survival compared with treatment using paclitaxel chemotherapy. The immune checkpoint inhibitor, nivolumab, improved survival in refractory gastric cancer. Recent studies in gastric cancer clarify the optimal preoperative chemotherapy regimen and the use of PET scan as a response measure of preoperative therapy in esophagogastric cancer, and the role of targeted agents and immune checkpoint inhibitors in metastatic disease.

New drugs for pain management in advanced cancer patients.

PubMed

Mercadante, Sebastiano

2017-04-01

Advanced cancer patients represent a frail population, often requiring aggressive pain management, particularly in the late stage of disease, when untreated pain is one the most important causes of suffering. Areas covered: In the last decade, a series of new analgesics have been introduced in the market to offer additional options amongst existent drugs. The characteristics of these drugs, their efficacy and tolerability are examined on the basis of existent studies. Expert opinion: Although new analgesic preparations have been developed in recent years, no specific drug has provided a better analgesic performance in comparison with others. Some technologies have been developed to increase the safety or decrease the opioid-related adverse effects, with some molecules providing extra-opioid analgesia. However, existing studies did not present relevant advantages over traditional opioids. The new formulations developed to provide a rapid and non-invasive analgesia for breakthrough pain have really changed the approach to this phenomenon, characterized by a specific temporal pattern requiring a short onset, and duration of the analgesic effect. The availability of new drugs, indeed, may enlarge the possibilities of individualizing treatment, according to specific clinical needs and individual response.

Improving drug addiction treatment in China.

PubMed

Tang, Yi-Lang; Hao, Wei

2007-07-01

To illustrate the current situation and problems of drug addiction in treatment China and propose suggestions. A descriptive study based on literature searched from Medline and the China National Knowledge Infrastructure database (1996-2007) and hand-picked references. Since the re-emergence of drug addiction in China in the early 1990s, there has been tremendous progress in drug addiction treatments in China, especially treatments for opiate addiction. However, many problems and challenges remain for improvement, including widespread negative attitudes towards drug abuse and drug-dependent individuals, the lack of evidence-based data on the efficacy of Chinese traditional medicine and the lack of a comprehensive and integrated system to organize all treatment resources and monitor treatment progress. The authors discuss the challenges that impede effective treatments of drug addiction and some suggestions are proposed. Implementing these suggestions can improve the outcome of treatment of drug-dependent individuals and benefit the whole society. China faces substantial drug addiction problems that appear to be worsening with time. Although much progress in drug addiction treatment has been made, improvement in many aspects is needed urgently.

Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer.

PubMed

Kaur, Paranjeet; Khatik, Gopal L

2016-01-01

Prostate cancer (PCa) is a leading cause of death in men worldwide. The main reason for the progression of prostate cancer is identified as over activation of androgen receptor (AR) through androgens. Its development can be diagnosed by monitoring the prostate specific antigen (PSA). Treatment of PCa includes prostatectomy, radiotherapy, and chemotherapy, among them chemotherapy is normally employed in early and advanced prostate cancer. Chemotherapy mainly includes two classes of drugs which are steroidal and non-steroidal antiandrogens. The non-steroidal classes of compounds are preferred over steroidal because they are relatively safe, cost effective and diverse. Non-steroidal drugs are commonly used for the treatment of PCa, however these drugs are associated with serious side effects and acquired resistance. So researchers are working in the direction to develop better analogue which can address the issue related to resistant type of prostate cancer. This review discusses the advancement in the non-steroidal antiandrogens which offers a better potential in the treatment of prostate cancer.

Illegal drugs in Grenada: arrests and drug treatment from 2001-2009.

PubMed

Fagorala, A

2013-09-01

Illegal drug use and abuse has increased in the Caribbean since the 1990s. In Grenada, statistical indicators such as admission rates to treatment facilities and drug arrests have provided evidence for the increased rates of illegal drug use and abuse. This study reviewed these statistical indicators and explored drug treatment options in Grenada from 2001 to 2009. A search of statistical records from the Drug Control Secretariat and the Grenada Drug Information Network/National Observatory on Drugs (GRENDIN/NOD) was performed. Literature review of relevant articles from search engines was used to support findings. Additionally, semi-structured interviews of key stakeholders from government and health agencies involved in drug prevention in Grenada were conducted to obtain information on recent developments surrounding drug arrests and treatments in Grenada. From 2001 to 2009, there were a 118% and a 23% increase in the arrest rate for males and females,respectively. There was also an increase in demand for drug treatment at the sole drug treatment facility. Preventive measures in schools and several forms of media programmes have raised awareness. However,drug use/abuse/activities still persist at a significant rate. Programmes that target improvement of treatment facilities and increased inter-agency collaboration may be successful in enhancing drug arrests and treatments.

Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments

PubMed Central

Carroll, Marilyn E.; Smethells, John R.

2016-01-01

The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments. PMID:26903885

Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments.

PubMed

Carroll, Marilyn E; Smethells, John R

2015-01-01

The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.

Management of treatment-related toxicities in advanced medullary thyroid cancer.

PubMed

Brose, Marcia S; Bible, Keith C; Chow, Laura Q M; Gilbert, Jill; Grande, Carolyn; Worden, Francis; Haddad, Robert

2018-05-01

Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team. Copyright © 2018. Published by Elsevier Ltd.

Episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery - recent research advances and patents.

PubMed

Gilger, Brian C; Mandal, Abhirup; Shah, Sujay; Mitra, Ashim K

2014-01-01

Subconjunctival/episcleral, intrascleral, and suprachoroidal routes of drug delivery for treatment of posterior segment eye diseases have become more feasible and popular in the past few years. These routes have the advantage of bypassing the main barriers to topical drug penetration, the ocular surface epithelium, the conjunctivallymphatics, and in the case of deep intrascleral and suprachoroidial delivery, the sclera barrier. Many ocular drug delivery application devices, drug delivery methods, and therapeutics that have been developed for intravitreal use can also be used subconjunctivally, intrasclerally, and in the suprachoroidal space. Alternatively, site-specific devices, such microneedles, and therapeutics, such as hydrogel matrices, have been developed to enhance ocular drug delivery. This manuscript will review the recent research advances and patents on episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery.

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

PubMed

Sharpe, Martyn A; Livingston, Andrew D; Gist, Taylor L; Ghosh, Pardip; Han, Junyan; Baskin, David S

2015-09-01

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

PubMed Central

Sharpe, Martyn A.; Livingston, Andrew D.; Gist, Taylor L.; Ghosh, Pardip; Han, Junyan; Baskin, David S.

2015-01-01

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P+-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models. PMID:26501110

Drug Abuse Treatment in Prisons. Treatment Research Report.

ERIC Educational Resources Information Center

National Inst. for Advanced Studies, Washington, DC.

This report, based on a 1979 national survey of drug abuse treatment programs in the prisons of the 50 states and the District of Columbia, presents data on 160 operational programs. Descriptive information on the identification of drug-dependent inmates and the provision of drug abuse treatment by state adult correctional institutions is…

Potential drug therapies for the treatment of fibromyalgia.

PubMed

Lawson, Kim

2016-09-01

Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

Pharmacokinetic drug evaluation of pazopanib for the treatment of uterine leiomyosarcomas.

PubMed

Ferrero, Simone; Leone Roberti Maggiore, Umberto; Aiello, Nicoletta; Barra, Fabio; Ditto, Antonino; Bogani, Giorgio; Raspagliesi, Francesco; Lorusso, Domenica

2017-08-01

Uterine leiomyosarcomas (ULMS) represent 1.3% of all uterine malignant tumors. Surgery is the curative treatment for patients with early stage disease. In case of advanced, persistent or recurrent tumor, chemotherapy represents the standard of care, but these patients have a poor prognosis. As the results with available therapies are far from being satisfactory, research is focusing on identification of new compounds. In 2012 the Food and Drug Administration (FDA) licensed pazopanib for the treatment of advanced soft-tissue sarcomas failing previous chemotherapy. Areas covered: The aim of this article is to review the literature on the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of the tyrosine kinase inhibitor (TKI), pazopanib in the treatment of ULMS. Expert opinion: The discovery of some relevant signalling pathways in LMS cells led to the development of new targeted drugs with promising results in the management of these tumors. Pazopanib is a multi-target second-generation TKI with activity against growth factors involved in angiogenesis. It has shown promising results both in terms of efficacy and safety, as shown in the EORTC 62043 Study and the PALETTE trial. Further studies are awaited to evaluate its efficacy in uterine leiomyosarcomas.

Current challenges and emerging drug delivery strategies for the treatment of psoriasis.

PubMed

Hoffman, Melissa B; Hill, Dane; Feldman, Steven R

2016-10-01

Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.

40 CFR 35.2101 - Advanced treatment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Advanced treatment. 35.2101 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2101 Advanced treatment. Projects proposing advanced treatment shall be awarded grant assistance only after the project has been...

Advances in phage display technology for drug discovery.

PubMed

Omidfar, Kobra; Daneshpour, Maryam

2015-06-01

Over the past decade, several library-based methods have been developed to discover ligands with strong binding affinities for their targets. These methods mimic the natural evolution for screening and identifying ligand-target interactions with specific functional properties. Phage display technology is a well-established method that has been applied to many technological challenges including novel drug discovery. This review describes the recent advances in the use of phage display technology for discovering novel bioactive compounds. Furthermore, it discusses the application of this technology to produce proteins and peptides as well as minimize the use of antibodies, such as antigen-binding fragment, single-chain fragment variable or single-domain antibody fragments like VHHs. Advances in screening, manufacturing and humanization technologies demonstrate that phage display derived products can play a significant role in the diagnosis and treatment of disease. The effects of this technology are inevitable in the development pipeline for bringing therapeutics into the market, and this number is expected to rise significantly in the future as new advances continue to take place in display methods. Furthermore, a widespread application of this methodology is predicted in different medical technological areas, including biosensing, monitoring, molecular imaging, gene therapy, vaccine development and nanotechnology.

Recent advances in light-responsive on-demand drug-delivery systems.

PubMed

Linsley, Chase S; Wu, Benjamin M

2017-02-01

The convergence of wearable sensors and personalized medicine enhance the ability to sense and control the drug composition and dosage, as well as location and timing of administration. To date, numerous stimuli-triggered smart drug-delivery systems have been developed to detect changes in light, pH, temperature, biomolecules, electric field, magnetic field, ultrasound and mechanical forces. This review examines the major advances within the last 5 years for the three most common light-responsive drug delivery-on-demand strategies: photochemical, photoisomerization and photothermal. Examples are highlighted to illustrate progress of each strategy in drug delivery applications, and key limitations are identified to motivate future research to advance this important field.

The state of support for research on the epidemiology, prevention, and treatment of drug use and drug use disorders in the USA.

PubMed

Sloboda, Zili

2012-01-01

This article describes the challenge of sustaining a balanced agenda for drug use research in the USA to advance understanding of the nature and extent of drug use and drug use disorders in a population; the processes and mechanisms that underlie onset, continuing, and stopping drug dependence; how to effectively prevent the onset of and early drug use as well as the social and health consequences of such use; and how to treat and maintain those with drug use disorders. This review concludes with recommendations to achieve sustained stability of funding for and to promote the progress of epidemiologic, prevention, and treatment policy research.

Stigma, discrimination, treatment effectiveness, and policy: public views about drug addiction and mental illness.

PubMed

Barry, Colleen L; McGinty, Emma E; Pescosolido, Bernice A; Goldman, Howard H

2014-10-01

Public attitudes about drug addiction and mental illness were compared. A Web-based national survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support in regard to drug addiction and mental illness. Respondents held significantly more negative views toward persons with drug addiction. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them. Respondents were more willing to accept discriminatory practices against persons with drug addiction, more skeptical about the effectiveness of treatments, and more likely to oppose policies aimed at helping them. Drug addiction is often treated as a subcategory of mental illness, and insurance plans group them together under the rubric of "behavioral health." Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches to reducing stigma and advancing public policy.

Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

PubMed

Patel, Mayur M; Patel, Bhoomika M

2017-02-01

CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

Drugs in development for toxoplasmosis: advances, challenges, and current status.

PubMed

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

Drugs in development for toxoplasmosis: advances, challenges, and current status

PubMed Central

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

Multiple treatment comparison of seven new drugs for patients with advanced malignant melanoma: a systematic review and health economic decision model in a Norwegian setting

PubMed Central

Pike, Eva; Hamidi, Vida; Saeterdal, Ingvil; Odgaard-Jensen, Jan; Klemp, Marianne

2017-01-01

Objective To assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting. Design A multiple technology assessment. Patients Patients with advanced malignant melanoma aged 18 or older. Data sources A systematic search for randomised controlled trials in relevant bibliographic databases. Methods We performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation. Results Monotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors. PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy. BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost. Conclusions None of the drugs investigated can be considered cost-effective at what

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Carrier-Based Drug Delivery System for Treatment of Acne

PubMed Central

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment.

PubMed

Ding, Chendi; Tong, Ling; Feng, Jing; Fu, Jiajun

2016-12-20

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

Recent advances in the treatment of hepatitis C.

PubMed

Dhingra, Abhinav; Kapoor, Saloni; Alqahtani, Saleh A

2014-10-01

Hepatitis C virus (HCV) therapeutics is amidst a revolution. With the recent approval of sofosbuvir (Sovaldi) and simeprevir (Olysio), clinicians and patients started to recognize that for the first time in the history, hepatitis C can be cured in a majority of patients without interferon. These new regimens are safe, and have excellent efficacy and minimal adverse events. Sofosbuvir, a nucleotide analogue (NS5B polymerase inhibitor), is a potent drug with excellent tolerability and pan-genotypic activity with a high barrier to resistance. Simeprevir, a second-generation protease inhibitor which inhibits the initial cleavage of the HCV poly-protein by the NS3/4A protease. Simeprevir has been evaluated in clinical trials in combination with interferon and ribavirin based therapy and also in the COSMO trial in combination with sofosbuvir. More directly acting antiviral therapy drugs are in the pipeline with several drugs being expected to be approved by the FDA in late 2014. Although these drugs have excellent efficacy, they are more costly. The price of these drugs limits treatments of many patients in the world especially in countries with limited economic resources. However, with the availability of a variety of excellent directly acting antivirals (DAAs) in the near future, hopefully many patients would be able to afford the treatment. The future in HCV therapy will focus on special groups of patients who were excluded from initial HCV clinical trials such as post-liver transplant HCV recurrence, patients with HCV/HIV co-infection, and patients with advanced cirrhosis.

Refining the treatment of advanced nonsmall cell lung cancer

PubMed Central

Ogita, Shin; Wozniak, Antoinette J

2010-01-01

Metastatic nonsmall cell lung cancer (NSCLC) is a debilitating and deadly disease with virtually no chance for long-term survival. Chemotherapy has improved both survival and quality of life for patients with advanced disease. Overall survival of patients with metastatic NSCLC has gradually increased from 8 to 12 months over the past three decades with the introduction of new chemotherapeutic drugs and agents directed at novel targets in the cancer cell. Epidermal growth factor receptor and vascular endothelial growth factor are two such targets. Recent developments also include treatment based on histology and the use of maintenance therapy. It has been recognized that lung cancer is a very complex disease. It is common practice to include a number of scientific correlative studies in the design of clinical trials in order to determine predictive markers of benefit from treatment. This article will review the current approach to the treatment of advanced NSCLC including the use of chemotherapy and molecularly targeted agents. Future directions including the use of potentially predictive biomarkers and innovative clinical trials aimed at a more individualized approach to treatment will also be discussed. PMID:28210103

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright �

Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran

PubMed Central

2012-01-01

Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557

Recent advances in light-responsive on-demand drug-delivery systems

PubMed Central

Linsley, Chase S; Wu, Benjamin M

2017-01-01

The convergence of wearable sensors and personalized medicine enhance the ability to sense and control the drug composition and dosage, as well as location and timing of administration. To date, numerous stimuli-triggered smart drug-delivery systems have been developed to detect changes in light, pH, temperature, biomolecules, electric field, magnetic field, ultrasound and mechanical forces. This review examines the major advances within the last 5 years for the three most common light-responsive drug delivery-on-demand strategies: photochemical, photoisomerization and photothermal. Examples are highlighted to illustrate progress of each strategy in drug delivery applications, and key limitations are identified to motivate future research to advance this important field. PMID:28088880

A comparison of drug resistances of targeted drugs for advanced renal cell cancer approved by the Food and Drug Administration: A meta-analysis of randomized clinical trials.

PubMed

Guo, Ming; Cao, Yunsong; Yang, Jingzhe; Zhang, Jingfeng

2016-10-01

The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis. For overall present, the mean 6-month progression-free survival rates were 65.4%, 49.3%, 60.6%, 70.3%, 62.6%, 41.6%, 38.2%, 66.1%, 43.1%, and 17.9% for sunitinib, sorafenib, pazopanib, axitinib, bevacizumab plus interferon (IFN)-a, everolimus, temsirolimus, temsirolimus plus bevacizumab, IFN-a, and placebo, respectively. For indirect comparison, two combined therapies (bevacizumab plus IFN-a and temsirolimus plus bevacizumab) and sunitinib were of less ability of drug resistance. The risk ratio of sunitinib therapy was 3.64 (95% confidence interval [CI] [3.12, 4.25]), the risk ratio of temsirolimus plus bevacizumab therapy was 3.68 (95% CI [3.14, 4.33]), and the risk ratio of bevacizumab plus IFN-a therapy was 3.49 (95% CI [2.99, 4.06]). Our results support that combination of targeted therapies might be a novel strategy against advanced renal cell carcinomas.

Factors related to Psychosocial Barriers to Drug Treatment among Chinese Drug Users

PubMed Central

Kelly, Brian C; Liu, Tieqiao; Zhang, Guanbai; Hao, Wei; Wang, Jichuan

2014-01-01

Although substance abuse treatment has been considerably scaled up in China, impediments to accessing these services remain among drug users. The authors examine the primary psychosocial barriers to drug treatment in this population and evaluate factors associated with these barriers. Barriers to accessing drug treatment were measured using the Barriers to Treatment Inventory (BTI). A Structural Equation Model was used to examine whether the internal barriers were associated with treatment history and frequent methamphetamine use as well as how demographic characteristics influence such barriers. We found four primary factors of internal barriers to drug treatment – absence of problem, negative social support, fear of treatment, and privacy concerns – to fit well. Demographic factors, notably age and employment status, indirectly influence barriers to treatment via other factors. Frequency of methamphetamine use and drug treatment history are directly associated with the absence of problem and negative social support dimensions of the BTI, and it is through these pathways that demographic factors such as age and employment status shape barriers to treatment. The findings indicate that perceived absence of a problem and negative social support are the barriers most influenced by the personal domains of Chinese drug users’ lives. Efforts to engage drug users in China about drug treatment options may consider how these barriers are differentially perceived in order to effectively reach this population. PMID:24813554

Drug Dependence Treatment Awareness among Japanese Female Stimulant Drug Offenders

PubMed Central

Yatsugi, Shinzo; Fujita, Koji; Kashima, Saori; Eboshida, Akira

2016-01-01

Few stimulant drug users receive adequate treatment. This cross-sectional study describes the characteristics of female drug offenders that use stimulants and clarifies the factors related to the awareness of treatment for drug dependencies. We included 80 females imprisoned due to stimulant control law violations from 2012 to 2015. The characteristics of the female prisoners were stratified according to various treatment awareness levels, and associations between each characteristic and treatment awareness were evaluated using logistic regression models. The average period of stimulant drug use was 17.7 years. Participants imprisoned for the second time were significantly more likely to consider treatment compared to those imprisoned only once: odds ratio (OR) = 3.2 (95% confidence interval (CI): 1.0–10.7). This elevated OR was diluted in repeat offenders. Participants who had experienced multiple aftereffects (≥7) or serious depressive symptoms were also more likely to consider treatment: OR = 6.1 (95% CI: 1.8–20.8) and OR = 2.5 (95% CI: 1.0–6.2), respectively. Second-time stimulant offenders or offenders who had experienced health problems were more likely to consider it important to receive drug dependence treatment. To overcome relapses of stimulant use, it is recommended that stimulant use offenders are encouraged to accept adequate treatment. PMID:27845738

Recent advances in ophthalmic drug delivery

PubMed Central

Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

2011-01-01

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

Advanced Materials and Processing for Drug Delivery: The Past and the Future

PubMed Central

Zhang, Ying; Chan, Hon Fai; Leong, Kam W.

2012-01-01

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

[Prophylactic drug treatment of migraine].

PubMed

Massiou, H; Bousser, M-G

2005-07-01

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. Based on the results of published controlled trials, the main prophylactic drugs are some beta-blockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, sodium valproate and topiramate. With these drugs, the frequency of attacks can be reduced by half in 50 percent of patients. Some less evaluated substances such as aspirin, DHE, indoramine, and angiotensin II inhibitors may be useful. The decision to treat with drugs and the choice of a prophylactic drug are made together with the patient. The superiority of one major drug over another has never been demonstrated in a comparative trial, thus the choice of the drug to start with depends on the possible side effects and contraindications, the characteristics of the migraine attacks, and the associated morbidities and possible interactions with abortive medications. Doses should be increased gradually, in order to reach the recommended daily dose, only if tolerance permits. Treatment efficacy has to be assessed after 2 or 3 months, and in case of failure or poor tolerance, another treatment should be started. If the treatment is successful, it should be continued for 6 to 12 months, and then tapered off. The moderate efficacy and the frequency of the side effects observed with prophylactic drugs explain the high rate of withdrawals. Some patients nevertheless dramatically improve, warranting trying several drugs successively in order to find the most appropriate one.

Advances and Progress in Chagas Disease Drug Discovery.

PubMed

Ferreira, Leonardo G; de Oliveira, Marcelo T; Andricopulo, Adriano D

2016-01-01

Chagas disease represents a serious burden for millions of people worldwide. Transmitted by the protozoan parasite Trypanosoma cruzi, this neglected tropical disease causes more than 10,000 deaths each year and is the main cause of heart failure in Latin America, where it is endemic. Although most cases are concentrated in Latin American countries, Chagas disease has been increasingly reported in non-endemic regions, where the low level of public awareness on the subject contributes to the growing prevalence of the disease. The available medicines are characterized by several safety and efficacy drawbacks that prevent millions of people, particularly those with advanced disease, from receiving adequate treatment. This urgent need has stimulated the emergence of diverse initiatives dedicated to the research and development (R&D) of novel therapeutic agents for Chagas disease. Public-private partnerships have been responsible for a significant increase in the investments in R&D programs and major advancements have been achieved over the past ten years. A number of collaborative projects have been leveraged by this organizational model, which privileges sharing of data, expertise, and resources between research institutions and pharmaceutical companies. Among the current strategies employed by these consortia, target-based and phenotypic screenings have achieved the most promising results. This article provides an overview on the current status and recent advances in Chagas disease drug discovery.

Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

PubMed

Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

2018-06-04

Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments.

PubMed

Boleda, M A Rosa; Galceran, M A Teresa; Ventura, Francesc

2011-06-01

The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies ≥ 94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recent advances in (therapeutic protein) drug development

PubMed Central

Lagassé, H.A. Daniel; Alexaki, Aikaterini; Simhadri, Vijaya L.; Katagiri, Nobuko H.; Jankowski, Wojciech; Sauna, Zuben E.; Kimchi-Sarfaty, Chava

2017-01-01

Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016). PMID:28232867

Drug discovery for the treatment of leishmaniasis, African sleeping sickness and Chagas disease.

PubMed

2013-10-01

The trypanosomatid protozoa Leishmania, Trypanosoma brucei and Trypanosoma cruzi are the caustive agents of the human diseases respectively, leishmaniasis, African sleeping sickness and Chagas disease. Among the 17 'neglected tropical diseases' highlighted by WHO, progress towards the treatment of these diseases has improved in recent decades, as a result of increased awareness, the emergence of public-private research partnerships and advances in drug-discovery technologies and techniques. Despite this, the current therapies for these diseases have serious shortcomings and, as such, the need to develop novel drugs, improve diagnosis and control the spread of disease is of paramount importance. Future Medicinal Chemistry invited leading experts in the field to share their thoughts and opinions on the changing face of drug discovery in the pursuit of treatments for trypanosomatid-based diseases.

Recent advances in inorganic nanoparticle-based drug delivery systems.

PubMed

Murakami, Tatsuya; Tsuchida, Kunihiro

2008-02-01

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.

Advances in the treatment of polyarticular juvenile idiopathic arthritis

PubMed Central

Webb, Kate; Wedderburn, Lucy R.

2015-01-01

Purpose of review To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for further research. Recent findings There is evidence for an early, aggressive, treat-to-target approach for polyarticular JIA. Clinical disease activity criteria have been recently defined and validated, including criteria for inactive disease and the juvenile arthritis disease activity score (JADAS). There is a need for evidence-based, defined disease targets and biomarkers for prediction of response, including targets for remission induction, and guidelines on drug withdrawal. Recent treatment consensus plans and guidelines are discussed and compared, including the 2015 NHS England clinical policy statement, the 2014 Childhood Arthritis and Rheumatology Research Alliance (CARRA) treatment plans and the 2011 American College of Rheumatology (ACR) guidelines. Evidence for new agents such as tocilizumab, rituximab, golimumab, ustekinumab, certolizumab and tofacitinib is promising: the recent clinical trials are summarized here. Stratification of individual patient treatment remains a goal, and predictive biomarkers have been shown to predict success in the withdrawal of methotrexate therapy. Summary There are promising advances in the treatment approaches, disease activity criteria, clinical guidelines, pharmaceutical choices and individually stratified therapy choices for polyarticular JIA. PMID:26147756

Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

PubMed

Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

2017-01-01

Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

Issues In-Depth: Advancing Understanding of Drug Addiction and Treatment

ERIC Educational Resources Information Center

Miller, Roxanne Greitz

2009-01-01

While most school districts utilize a drug abuse resistance curriculum, as science teachers, it is our responsibility to understand the science behind drug addiction in order to most effectively educate our students against drug abuse. In the last two decades, increases in scientific technology have permitted significant discoveries surrounding…

Novel Pieces for the Emerging Picture of Sulfoximines in Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues of Marketed Drugs and Advanced Clinical Candidates.

PubMed

Sirvent, Juan Alberto; Lücking, Ulrich

2017-04-06

Sulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan-CDK inhibitor), BAY 1143572 (P-TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal-chemistry-relevant properties of sulfoximines. Herein we report the synthesis and in vitro characterization of a variety of sulfoximine analogues of marketed drugs and advanced clinical candidates to gain a better understanding of this neglected functional group and its potential in drug discovery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Innovations in management of cardiac disease: drugs, treatment strategies and technology.

PubMed

Foëx, P

2017-12-01

Within the last generation, the management of patients with heart disease has been transformed by advances in drug treatments, interventions and diagnostic technologies. The management of arterial hypertension saw beta-blockers demoted from first- to third-line treatment. Recent studies suggest that the goal of treatment may have to change to lower systolic blood pressures to prevent long-term organ damage. Today less than 15% of coronary revascularizations are surgical and more than 85% are done by interventional cardiologists inserting coronary stents. Thus, managing patients on dual antiplatelet therapy has become an important issue. With new generations of coronary stents, recommendations are changing fast. In the past, decisions concerning non-cardiac surgery after acute myocardial infarction were based on the delay between infarction and non-cardiac surgery. Today, the main concern is the patient's status in respect of dual antiplatelet therapy after primary percutaneous intervention. There have been advances in the management of heart failure but new drugs (ivabradine, sacubitril/valsartan) and cardiac resynchronization are recommended only in patients with an ejection fraction below 35% on optimal medication. Heart failure remains a major perioperative risk factor. Prospective studies have shown that troponin elevations represent myocardial injury (not necessarily myocardial infarction), are mostly silent and are associated with increased 30-day mortality. Monitoring (troponin assays) for myocardial injury in non-cardiac surgery (MINS) seems increasingly justified. The treatment of MINS needs further research. Technological advances, such as intelligent, portable monitors benefit not only patients with cardiac disease but all patients who have undergone major surgery and are on the wards postoperatively. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please

Multiple treatment comparison of seven new drugs for patients with advanced malignant melanoma: a systematic review and health economic decision model in a Norwegian setting.

PubMed

Pike, Eva; Hamidi, Vida; Saeterdal, Ingvil; Odgaard-Jensen, Jan; Klemp, Marianne

2017-08-21

To assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting. A multiple technology assessment. Patients with advanced malignant melanoma aged 18 or older. A systematic search for randomised controlled trials in relevant bibliographic databases. We performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation. Monotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors.PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy.BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost. None of the drugs investigated can be considered cost-effective at what has normally been considered a reasonable willingness-to-pay (WTP) in

Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs.

PubMed

Tfelt-Hansen, Peer C; Pihl, Thomas; Hougaard, Anders; Mitsikostas, Dimos D

2014-03-01

The development of sumatriptan, more than 20 years ago, added substantially to the characterization of 5-hydroxytryptamine (5-HT) receptors and their relevance to acute migraine therapy. Recently, 5-HT1F receptor agonists, with no vascular effects, have shown efficacy in the treatment of migraines. This evaluation reviews the recent advances in acute migraine therapy targeting the 5-HT receptor. Specifically, the authors review the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of 5-HT1F receptor agonists and new formulations of sumatriptan and dihydroergotamine (DHE). Lasmiditan, a non-vascular acting 5-HT1F receptor agonist, is effective in migraine but causes central nervous system-related adverse events, which may considerably limit its clinical use. The efficacy of transdermal sumatriptan is too low for general use in migraine. Intranasal sumatriptan powder could be a step forward compared with oral sumatriptan, but comparative trials are needed. Orally inhaled DHE has a very quick systemic absorption but the onset of effect in migraine is relatively slow with a maximum effect after 2 h. In contrast, orally inhaled DHE results in a low incidence of recurrence. None of these reviewed treatments are likely to fulfill patients' expectations, and the advancement of acute migraine drugs should likely depend on different mechanisms from current 5-HT-related drugs.

Advances in the use of nanocarriers for cancer diagnosis and treatment

PubMed Central

Vieira, Débora Braga; Gamarra, Lionel Fernel

2016-01-01

ABSTRACT The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy. PMID:27074238

Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

PubMed

Mooney, Michael A; Simon, Elias D; Little, Andrew S

2016-01-01

The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

Porous silicon advances in drug delivery and immunotherapy

PubMed Central

Savage, D; Liu, X; Curley, S; Ferrari, M; Serda, RE

2013-01-01

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. PMID:23845260

Drug treatment or alleviating the negative consequences of imprisonment? A critical view of prison-based drug treatment in Denmark.

PubMed

Kolind, Torsten; Frank, Vibeke Asmussen; Dahl, Helle

2010-01-01

The availability of prison-based drug treatment has increased markedly throughout Europe over the last 15 years in terms of both volume and programme diversity. However, prison drug treatment faces problems and challenges because of the tension between ideologies of rehabilitation and punishment. This article reports on a study of four cannabis treatment programmes and four psychosocial drug treatment programmes in four Danish prisons during 2007. The data include the transcripts of 22 semi-structured qualitative interviews with counsellors and prison employees, prison statistics, and information about Danish laws and regulations. These treatment programmes reflect the 'treatment guarantee' in Danish prisons. However, they are simultaneously embedded in a new policy of zero tolerance and intensified disciplinary sanctions. This ambivalence is reflected in the experiences of treatment counsellors: reluctantly, they feel associated with the prison institution in the eyes of the prisoners; they experience severe opposition from prison officers; and the official goals of the programmes, such as making clients drug free and preparing them for a life without crime, are replaced by more pragmatic aims such as alleviating the pain of imprisonment felt by programme clients. The article concludes that at a time when prison-based drug treatment is growing, it is crucial that we thoroughly research and critically discuss its content and the restrictions facing such treatment programmes. One way of doing this is through research with counsellors involved in delivering drug treatment services. By so doing, the programmes can become more pragmatic and focused, and alternatives to prison-based drug treatment can be seriously considered.

Impact of treatment for depression on desire for hastened death in patients with advanced AIDS.

PubMed

Breitbart, William; Rosenfeld, Barry; Gibson, Christopher; Kramer, Michael; Li, Yuelin; Tomarken, Alexis; Nelson, Christian; Pessin, Hayley; Esch, Julie; Galietta, Michele; Garcia, Nerina; Brechtl, John; Schuster, Michael

2010-01-01

Despite the development of multi-drug regimens for HIV, palliative care and quality-of-life issues in patients with advanced AIDS remain important areas of clinical investigation. Authors assessed the impact of treatment for depression on desire for hastened death in patients with advanced AIDS. Patients with advanced AIDS (N=372) were interviewed shortly after admission to a palliative-care facility, and were reinterviewed monthly for the next 2 months. Patients diagnosed with a major depressive syndrome were provided with antidepressant treatment and reinterviewed weekly. Desire for hastened death was assessed with two questionnaire measures. Desire for death was highly associated with depression, and it decreased dramatically in patients who responded to antidepressant treatment. Little change in desire for hastened death was observed in patients whose depression did not improve. Although improved depression was not significantly associated with the use of antidepressant medication, those individuals prescribed antidepressant medication showed the largest decreases in desire for hastened death. Successful treatment for depression appears to substantially decrease desire for hastened death in patients with advanced AIDS. The authors discuss implications of these findings for palliative-care treatment and the physician-assisted suicide debate.

Impact of Treatment for Depression on Desire for Hastened Death in Patients With Advanced AIDS

PubMed Central

Breitbart, William; Rosenfeld, Barry; Gibson, Christopher; Kramer, Michael; Li, Yuelin; Tomarken, Alexis; Nelson, Christian; Pessin, Hayley; Esch, Julie; Galietta, Michele; Garcia, Nerina; Brechtl, John; Schuster, Michael

2013-01-01

Background Despite the development of multi-drug regimens for HIV, palliative care and quality-of-life issues in patients with advanced AIDS remain important areas of clinical investigation. Objective Authors assessed the impact of treatment for depression on desire for hastened death in patients with advanced AIDS. Method Patients with advanced AIDS (N=372) were interviewed shortly after admission to a palliative-care facility, and were reinterviewed monthly for the next 2 months. Patients diagnosed with a major depressive syndrome were provided with antidepressant treatment and reinterviewed weekly. Desire for hastened death was assessed with two questionnaire measures. Results Desire for death was highly associated with depression, and it decreased dramatically in patients who responded to antidepressant treatment. Little change in desire for hastened death was observed in patients whose depression did not improve. Although improved depression was not significantly associated with the use of antidepressant medication, those individuals prescribed antidepressant medication showed the largest decreases in desire for hastened death. Discussion Successful treatment for depression appears to substantially decrease desire for hastened death in patients with advanced AIDS. The authors discuss implications of these findings for palliative-care treatment and the physician-assisted suicide debate. PMID:20332284

Phase II trial suggests new drug can shrink tumors in advanced ovarian cancer | Center for Cancer Research

Cancer.gov

In an ongoing phase II trial led by Jung-Min Lee, M.D., an Investigator in CCR’s Women’s Malignancies Branch, using the drug prexasertib led to decreases in tumor size in patients with advanced ovarian cancer, known as high-grade serious ovarian carcinoma, who currently have limited treatment options. Read more…

Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes.

PubMed

Tseng, Yuan-Yun; Su, Chen-Hsing; Yang, Shun-Tai; Huang, Yin-Chen; Lee, Wei-Hwa; Wang, Yi-Chuan; Liu, Shou-Cheng; Liu, Shih-Jung

2016-09-13

Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy.The chemotherapeutic agents were rapidly released from the 50:50 PLGA nanofibres after implantation, followed by the release of combretastatin (approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug concentrations remained higher in brain tissues than in the blood for more than 8 weeks. The experimental results, including attenuated malignancy, retarded tumour growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes more efficiently retarded the tumour growth and attenuated the malignancy of C6 glioma-bearing rats. Moreover, the addition of combretastatin did not significantly change the drug release behaviour of the BIC/PLGA nanofibrous membranes. The present advanced and novel interstitial chemotherapy and targeted treatment provide a potential strategy and regimen for treating GBM.

Rapid and large-scale implementation of HCV treatment advances in France, 2007-2015.

PubMed

Brouard, Cécile; Boussac-Zarebska, Marjorie; Silvain, Christine; Durand, Julien; de Lédinghen, Victor; Pillonel, Josiane; Delarocque-Astagneau, Elisabeth

2017-12-20

The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015. Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.

Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

PubMed

Stewart, Michael W

2016-08-25

Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.

New drugs in treatment of asthma.

PubMed

Weisberg, S C; Kaiser, H B

1976-09-01

Therapy for bronchial asthma should be preventive when possible. Around-the-clock treatment with theophylline is a new way of using an old drug. Beta2-adrenergic receptor stimulators, cromolyn sodium, and steroids in aerosol form are new drugs that are useful in treatment of asthma. The good news with respect to drug treatment of asthma is that in addition to the old reliable medications which have provided good relief-including epinephrine, ephedrine, isoproterenol, aminophylline, and steroids given orally and parenterally-new drugs are available which have been extremely helpful in controlling symptoms in many patients. The bad news is that none of the new agents is a panacea and that many of them have significant undesirable side effects. It is the physician's responsibility to be wary of the new drugs for asthma and to use them appropriately.

Porous silicon advances in drug delivery and immunotherapy.

PubMed

Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

2013-10-01

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advances in non-dopaminergic treatments for Parkinson's disease

PubMed Central

Stayte, Sandy; Vissel, Bryce

2014-01-01

Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

Clinical features and treatment of drug fever caused by anti-tuberculosis drugs.

PubMed

Fang, Yong; Xiao, Heping; Tang, Shenjie; Liang, Li; Sha, Wei; Fang, Yuanyuan

2016-07-01

Tuberculosis is a major global health problem. However, anti-tuberculosis drug treatment has many adverse effects, such as drug-caused fever. The aim of this study was to investigate the clinical features and treatments of anti-tuberculosis drugs-induced fever. A total of 78 inpatients and outpatients with pulmonary tuberculosis accompanied by drug fever during the anti-tuberculosis treatment were analysed retrospectively from April 2006 to March 2013. Among the anti-tuberculosis drugs that caused the drug fever, rifampicin was the most common one, followed by para-aminosalicylic and pyrazinamide. The symptoms occurred within 2 months after treatment, mainly in the 1-3 weeks, and the main symptom was high fever with body temperature above 39°C. The accompanying symptoms include rash, chills, headache, stuffy nose, runny nose, nausea, vomiting and joint pain. Routine blood examination found that eosinophilia increased in 15 cases and decreased in another 15. Among 63 patients who underwent liver function tests, there were 10 cases of abnormal function and 4 cases of liver damage. When the drug fever was suspected, the measure of withdrawal was taken first. All the suspected drugs were withdrawn in 59 cases, while gradual withdrawal was conducted in 19 cases. Patients with complications were first treated in accordance with the principles of complications treatment and then were gradually given some drugs after recovery. The patients without complications were gradually given some drugs after the body temperature was back to normal. Drug fever is an allergic reaction, the resolution of which depends on whether it was accompanied by liver damage and/or rash or not. © 2014 John Wiley & Sons Ltd.

Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

NASA Astrophysics Data System (ADS)

Islam, Nazrul; Ferro, Vito

2016-07-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

Recent advances in the diagnosis of drug allergy.

PubMed

Primeau, M N; Adkinson, N F

2001-08-01

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.

Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice

PubMed Central

Rogers, Justin T.; Liu, Chia-Chen; Zhao, Na; Wang, Jian; Putzke, Travis; Yang, Longyu; Shinohara, Mitsuru; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2017-01-01

Aging is accompanied by increased neuroinflammation, synaptic dysfunction and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events. By comparing young (3 months), middle-aged (18 months), aged (24 months) and advanced-aged wild-type mice (30 months), we found that the levels of an astrocytic marker, GFAP, progressively increased after 18 months of age, which preceded the decreases of the synaptic marker PSD-95. Hippocampal long-term potentiation (LTP) was also suppressed in an age-dependent manner, where significant deficits were observed after 24 months of age. Fear conditioning tests demonstrated that associative memory in the context and cued conditions was decreased starting at the ages of 18 and 30 months, respectively. When the mice were tested on hidden platform water maze, spatial learning memory was significantly impaired after 24 months of age. Importantly, subacute treatment with the anti-inflammatory drug ibuprofen suppressed astrocyte activation, and restored synaptic plasticity and memory function in advanced-aged mice. These results support the critical contribution of aging-related inflammatory responses to hippocampal-dependent cognitive function and synaptic plasticity, in particular during advanced aging. Our findings provide strong evidence that suppression of neuroinflammation could be a promising treatment strategy to preserve cognition during aging. PMID:28254590

Tuning model drug release and soft-tissue bioadhesion of polyester films by plasma post-treatment.

PubMed

Mogal, Vishal T; Yin, Chaw Su; O'Rorke, Richard; Boujday, Souhir; Méthivier, Christophe; Venkatraman, Subbu S; Steele, Terry W J

2014-04-23

Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils".

Stigma, Discrimination, Treatment Effectiveness and Policy Support: Comparing Public Views about Drug Addiction with Mental Illness

PubMed Central

Barry, Colleen L; McGinty, Emma Elizabeth; Pescosolido, Bernice; Goldman, Howard H.

2014-01-01

Objective This study compares current public attitudes about drug addiction with attitudes about mental illness. Methods A web-based national public opinion survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support. Results Respondents hold significantly more negative views toward persons with drug addiction compared to those with mental illness. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them on a job. Respondents were more willing to accept discriminatory practices, more skeptical about the effectiveness of available treatments, and more likely to oppose public policies aimed at helping persons with drug addiction. Conclusions Drug addiction is often treated as a sub-category of mental illness, and health insurance benefits group these conditions together under the rubric of behavioral health. Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches for advancing stigma reduction and public policy. PMID:25270497

Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook.

PubMed

Talebian, Sepehr; Foroughi, Javad; Wade, Samantha J; Vine, Kara L; Dolatshahi-Pirouz, Alireza; Mehrali, Mehdi; Conde, João; Wallace, Gordon G

2018-05-13

In spite of remarkable improvements in cancer treatments and survivorship, cancer still remains as one of the major causes of death worldwide. Although current standards of care provide encouraging results, they still cause severe systemic toxicity and also fail in preventing recurrence of the disease. In order to address these issues, biomaterial-based implantable drug delivery systems (DDSs) have emerged as promising therapeutic platforms, which allow local administration of drugs directly to the tumor site. Owing to the unique properties of biopolymers, they have been used in a variety of ways to institute biodegradable implantable DDSs that exert precise spatiotemporal control over the release of therapeutic drug. Here, the most recent advances in biopolymer-based DDSs for suppressing tumor growth and preventing tumor recurrence are reviewed. Novel emerging biopolymers as well as cutting-edge polymeric microdevices deployed as implantable antitumor DDSs are discussed. Finally, a review of a new therapeutic modality within the field, which is based on implantable biopolymeric DDSs, is given. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent advances in small molecule drug delivery.

PubMed

Kidane, Argaw; Bhatt, Padmanabh P

2005-08-01

The majority of new drugs, and new drug products, being developed and marketed by the pharmaceutical industry are small molecules. Oral administration remains the most common route of delivering such drugs, typically in the form of immediate-release tablets or capsules. While the immediate-release dosage forms dominate the market today, more specialized and rationalized products incorporating the concepts of drug delivery are being developed to overcome the physicochemical, physiological and pharmacological challenges inherent with the drugs, and to improve the treatment regimens for the patients. Today, these specialized concepts are increasingly being applied to first-generation products and not just products intended for the life cycle management of the franchise.

Advances in diagnosis and treatment of trigeminal neuralgia

PubMed Central

Montano, Nicola; Conforti, Giulio; Di Bonaventura, Rina; Meglio, Mario; Fernandez, Eduardo; Papacci, Fabio

2015-01-01

Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields

Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

PubMed

Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

2016-11-01

Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. Copyright © 2016 Elsevier B.V. All rights reserved.

New treatments for advanced cancer: an approach to prioritization

PubMed Central

Ferguson, J S J; Summerhayes, M; Masters, S; Schey, S; Smith, I E

2000-01-01

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point ‘relative effectiveness scale’, which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts. © 2000 Cancer Research Campaign PMID:11044348

Technological advances in precision medicine and drug development.

PubMed

Maggi, Elaine; Patterson, Nicole E; Montagna, Cristina

New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

Medical capsule robots: A renaissance for diagnostics, drug delivery and surgical treatment.

PubMed

Mapara, Sanyat S; Patravale, Vandana B

2017-09-10

The advancements in electronics and the progress in nanotechnology have resulted in path breaking development that will transform the way diagnosis and treatment are carried out currently. This development is Medical Capsule Robots, which has emerged from the science fiction idea of robots travelling inside the body to diagnose and cure disorders. The first marketed capsule robot was a capsule endoscope developed to capture images of the gastrointestinal tract. Today, varieties of capsule endoscopes are available in the market. They are slightly larger than regular oral capsules, made up of a biocompatible case and have electronic circuitry and mechanisms to capture and transmit images. In addition, robots with diagnostic features such as in vivo body temperature detection and pH monitoring have also been launched in the market. However, a multi-functional unit that will diagnose and cure diseases inside the body has not yet been realized. A remote controlled capsule that will undertake drug delivery and surgical treatment has not been successfully launched in the market. High cost, inadequate power supply, lack of control over drug release, limited space for drug storage on the capsule, inadequate safety and no mechanisms for active locomotion and anchoring have prevented their entry in the market. The capsule robots can revolutionize the current way of diagnosis and treatment. This paper discusses in detail the applications of medical capsule robots in diagnostics, drug delivery and surgical treatment. In diagnostics, detailed analysis has been presented on wireless capsule endoscopes, issues associated with the marketed versions and their corresponding solutions in literature. Moreover, an assessment has been made of the existing state of remote controlled capsules for targeted drug delivery and surgical treatment and their future impact is predicted. Besides the need for multi-functional capsule robots and the areas for further research have also been

Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

PubMed Central

Dyall, Julie; Coleman, Christopher M.; Hart, Brit J.; Venkataraman, Thiagarajan; Holbrook, Michael R.; Kindrachuk, Jason; Johnson, Reed F.; Olinger, Gene G.; Jahrling, Peter B.; Laidlaw, Monique; Johansen, Lisa M.; Lear-Rooney, Calli M.; Glass, Pamela J.; Hensley, Lisa E.

2014-01-01

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies. PMID:24841273

Admissions of injection drug users to drug abuse treatment following HIV counseling and testing.

PubMed

McCusker, J; Willis, G; McDonald, M; Lewis, B F; Sereti, S M; Feldman, Z T

1994-01-01

The outcomes of counseling and testing programs related to human immunodeficiency virus (HIV) infection and risk of infection among injection drug users (IDUs) are not well known or understood. A counseling and testing outcome of potential public health importance is attaining admission to drug abuse treatment by those IDUs who are either infected or who are at high risk of becoming infected. The authors investigated factors related to admission to drug abuse treatment among 519 IDUs who received HIV counseling and testing from September 1987 through December 1990 at a men's prison and at community-based testing sites in Worcester, MA. By June 1991, 123 of the 519 IDUs (24 percent) had been admitted to treatment. Variables associated with their admission included a long history of drug injection, frequent recent drug injection, cleaning injection equipment using bleach, prior drug treatment, and a positive HIV test result. Logistic regression analyses, controlling for effects of recruitment site, year, sex, and area of residence, generally confirmed the associations. IDUs in the study population who were HIV-infected sought treatment or were admitted to treatment more frequently than those who were not infected. The results indicate that access to drug abuse treatment should be facilitated for high-risk IDUs and for those who have begun to inject drugs recently.

Drug treatment of poststroke aphasia.

PubMed

Bakheit, A M O

2004-03-01

Impairment of language function (aphasia) is one of the most common neurological symptoms after stroke. Approximately one in every three patients who have an acute stroke will suffer from aphasia. The estimated incidence and prevalence of stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia often results in significant disability and handicap. It is a major obstacle for patients to live independently in the community. When recovery from aphasia occurs, it is usually incomplete and patients are rarely able to return to full employment and other social activities. Currently, the main treatment for aphasia is conventional speech and language therapy. However, the effectiveness of this intervention has not been conclusively demonstrated and empirical observations suggest that spontaneous biological recovery may explain most of the improvement in language function that occurs in aphasics. The generally poor prognosis of the severe forms of poststroke language impairment (Broca, Wernicke and global aphasia), coupled with the limited effectiveness of conventional speech and language therapy has stimulated the search for other treatments that may be used in conjunction with speech and language therapy, including the use of various drugs. Dopamine agonists, piracetam (Nootropil), amphetamines, and more recently donepezil (Aricept), have been used in the treatment of aphasia in both the acute and chronic phase. The justification for the use of drugs in the treatment of aphasia is based on two types of evidence. Some drugs, such as dextroamphetamine (Dexedrine), improve attention span and enhance learning and memory. Learning is an essential mechanism for the acquisition of new motor and cognitive skills, and hence, for recovery from aphasia. Second, laboratory and clinical data suggest that drug treatment may partially restore the metabolic function in the ischemic zone that surrounds the brain lesion and also has a neuroprotective effect following

Treatment Programs in the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

McCarty, Dennis; Fuller, Bret; Kaskutas, Lee Ann; Wendt, William W.; Nunes, Edward V.; Miller, Michael; Forman, Robert; Magruder, Kathryn M.; Arfken, Cynthia; Copersino, Marc; Floyd, Anthony; Sindelar, Jody; Edmundson, Eldon

2008-01-01

Drug abuse treatment programs and university-based research centers collaborate to test emerging therapies for alcohol and drug disorders in the National Drug Abuse Treatment Clinical Trials Network (CTN). Programs participating in the CTN completed organizational (n = 106 of 112; 95% response rate) and treatment unit surveys (n = 348 of 384; 91% response rate) to describe the levels of care, ancillary services, patient demographics, patient drug use and co-occurring conditions. Analyses describe the corporations participating in the CTN and provide an exploratory assessment of variation in treatment philosophies. A diversity of treatment centers participate in the CTN; not for profit organizations with a primary mission of treating alcohol and drug disorders dominate. Compared to N-SSATS (National Survey of Substance Abuse Treatment Services), programs located in medical settings are over-represented and centers that are mental health clinics are under-represented. Outpatient, methadone, long-term residential and inpatient treatment units differed on patients served and services proved. Larger programs with higher counselor caseloads in residential settings reported more social model characteristics. Programs with higher social model scores were more likely to offer self-help meetings, vocational services and specialized services for women. Conversely, programs with accreditation had less social model influence. The CTN is an ambitious effort to engage community-based treatment organizations into research and more fully integrate research and practice. PMID:17875368

Recent advances in malaria drug discovery.

PubMed

Lanteri, Charlotte A; Johnson, Jacob D; Waters, Norman C

2007-06-01

Malaria is responsible for over 300 million clinical cases annually and claims the lives of approximately 1-2 million. With a disease that has plagued humanity throughout history, one would think that better control measures would be in place to decrease the mortality and morbidity associated with malaria. Due to malaria drug resistance, an increase in the number of clinical infections and deaths is soon likely to be observed. Therefore, there is a push to identify and introduce new drug entities for malaria treatment and prophylaxis. In an effort to develop new malaria drugs, several different approaches have been implemented. These include the use of drug combinations of either new or existing antimalarials, exploitation of natural products, identification of resistance reversal or sensitizing agents and the targeting of specific malarial enzymes. Past experience has shown that introduction of the same chemical entities, such as quinolines and antifolates, results in only limited efficacy with resistance developing rapidly within one year of introduction. New approaches to drug discovery should identify novel chemotypes which circumvent the parasite's disposition to drug resistance. This review summarizes current efforts in malaria drug discovery as uncovered in recent patent literature.

A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer.

PubMed

Nelson, Michael H; Dolder, Christian R

2007-08-01

Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10-1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated.

24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing, and... consent forms signed by such household member that: (i) Requests any drug abuse treatment facility to...

24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing, and... consent forms signed by such household member that: (i) Requests any drug abuse treatment facility to...

24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing, and... consent forms signed by such household member that: (i) Requests any drug abuse treatment facility to...

24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing, and... consent forms signed by such household member that: (i) Requests any drug abuse treatment facility to...

24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing, and... consent forms signed by such household member that: (i) Requests any drug abuse treatment facility to...

Gender differences in prison-based drug treatment participation.

PubMed

Belenko, Steven; Houser, Kimberly A

2012-08-01

Prisons inmates have high rates of substance abuse and associated social and health problems, and a concomitant high need for drug treatment while incarcerated. Female inmates have an even greater treatment need, yet most inmates do not participate in treatment while incarcerated. Using data from a nationally representative sample of prison inmates, this article examines the impact of gender on prison treatment participation and gender differences in the factors associated with clinical treatment participation. Females were significantly more likely to participate in prison drug treatment than males, controlling for other factors. For both males and females, severity of drug problems predicted participation in treatment. For males but not females, race was associated with prison treatment participation, and among those with drug abuse or dependence, females with co-occurring mental health problems were more likely to participate in treatment. Implications for prison assessment and treatment policies, and future research, are discussed.

28 CFR 550.52 - Non-residential drug abuse treatment services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...

28 CFR 550.52 - Non-residential drug abuse treatment services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...

28 CFR 550.52 - Non-residential drug abuse treatment services.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...

28 CFR 550.52 - Non-residential drug abuse treatment services.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...

28 CFR 550.52 - Non-residential drug abuse treatment services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...

Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced Drug-Delivery Systems.

PubMed

Tahara, Yoshiro; Mukai, Sada-Atsu; Sawada, Shin-Ichi; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2015-09-09

A nanocarrier-integrated bottom-up method is a promising strategy for advanced drug-release systems. Self-assembled nanogels, which are one of the most beneficial nanocarriers for drug-delivery systems, are tectonically integrated to prepare nanogel-crosslinked (NanoClik) microspheres. NanoClik microspheres consisting of nanogel-derived structures (observed by STED microscopy) release "drug-loaded nanogels" after hydrolysis, resulting in successful sustained drug delivery in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

75 FR 42103 - Advancing the Development of Medical Products Used In the Prevention, Diagnosis, and Treatment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... Tropical Diseases; Public Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public... hearing to solicit general views and information from interested persons on issues related to advancing... prevention, diagnosis, and treatment of neglected tropical diseases. In particular, FDA is seeking these...

Comparison of drug treatment histories of single and multiple drug abusers in detox.

PubMed

Greberman, S B; Jasinski, D

2001-01-01

This study was undertaken to determine differences in previous treatment patterns in individuals currently using different numbers of substances. Medical records of 1198 inpatient detoxification (detox) admissions were analyzed. Numbers of past admissions to completed detox, methadone, or other types of drug abuse treatment were totaled and ranked to determine most frequent type. Within gender, treatment histories of single and multiple drug abusers usually do not differ. The one exception is male multiple drug abusers ages 26-30, who show increased admissions. Possible explanations are that men do not seek treatment before developing medical complications of addiction or until external factors influence admission. There were differences in treatment histories between genders in multiple drug abusers only. Before age 30, women reported increased treatment of certain types. Possible explanations are that treatment priority is given to women who are, or may be, pregnant. Also, younger men may not enter or complete treatment. Previous treatment history may influence many behaviors. The results of this study delineate several valuable indicators for assessing past history.

Latest advances in novel cannabinoid CB2 ligands for drug abuse and their therapeutic potential

PubMed Central

Yang, Peng; Wang, Lirong; Xie, Xiang-Qun

2012-01-01

The field of cannabinoid (CB) drug research is experiencing a challenge as the CB1 antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB2 drugs without CB1 psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB1 receptor was discovered predominantly in the brain, whereas the CB2 is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB2 receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB2 neurons activity remains controversial, the CB2 receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB2 ligands from the literature as well as patents. PMID:22300098

Advancements in drug development for diarrhea-predominant irritable bowel syndrome.

PubMed

Dothel, Giovanni; Barbaro, Maria Raffaella; Raschi, Emanuel; Barbara, Giovanni; De Ponti, Fabrizio

2018-03-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder characterized by a complex pathophysiology hampering optimal targeted drug development. Recent advances in our understanding of key underlying mechanisms prompted novel therapeutics including novel pharmacological approaches. Areas covered: This review summarizes the latest advancements in the pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and safety of medicinal products considering the recent harmonization of regulatory requirements by the FDA and the EMA. Expert opinion: The new 5-HT 3 receptor antagonist ramosetron appears a promising therapeutic approach devoid of significant adverse events, although it is presently unavailable in Western countries, most likely because of the precautionary approach taken by regulatory agencies with this drug class. New pharmacological concepts on full agonists/antagonists, mixed-receptor activity and novel drug targets may streamline the present drug pipeline along with the adherence on new regulatory guidelines on outcome measures. Eluxadoline can be taken as an example of this paradigm shift. It has now been granted marketing authorization for IBS-D on both sides of the Atlantic, but it is still considered as a second-line agent by the NICE. There is still much work to be done to fully cover clinical needs of patients with IBS-D.

Apatinib in gastric carcinoma: A case report of partial response for first-line treatment in advanced disease.

PubMed

Wang, Yaping; Bi, Minghong; Zhang, Haoran; Gao, Zhenyuan; Zhou, Hairong; Chang, Shu

2017-10-01

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, with a gradual increasing incidence throughout the world. Mostly GC is diagnosed in its late stage. To date, there is no usable standardized treatment regimen for patients with advanced GC. Apatinib mesylate, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China, October, 2014. Till now, there is no case report about apatinib as first-line treatment for patients with advanced GC in literature. We present an 83-year-old Chinese man with advanced gastric adenocarcinoma, who received apatinib as first-line option and obtained clinical benefit within 2 weeks. The lung metastases disappeared completely and the liver metastases shrank significantly. The patient's progression-free survival was 163 days and overall survival was 201 days. This paper reviews and discusses apatinib as a new targeted drug for patients with advanced GC by comparison with other effective molecular-targeted therapy. © 2016 John Wiley & Sons Australia, Ltd.

Recent advances in neonatal pharmacotherapy.

PubMed

Calhoun, Darlene A; Murthy, S Narasimha; Bryant, Bobby G; Luedtke, Sherry A; Bhatt-Mehta, Varsha

2006-04-01

To provide commentary and reviews and brief discussions in controversial or innovative recent advances in neonatal pharmacotherapy. To discuss cutting edge drug delivery systems that may become useful in neonatal drug delivery in the future. Articles were identified through searches of MEDLINE (1990-October 2005), key articles in the authors' files, and in some cases, through data generated and/or published by the author of a particular topic. Article selection and relevance to the topics under discussion was determined by individual authors. Therapeutic strategies addressed in this review include the use of hematopoietic growth factors including a simulated amniotic fluid preparation containing these growth factors for neonates with selected gastrointestinal problems, erythropoietin for neuroprotection following perinatal asphyxia, drug therapy advances in treatment of patent ductus arteriosus (PDA), evaluation of advances in transdermal drug delivery, and its potential application to neonates and advances in the treatment of persistent pulmonary hypertension (PPHN) of the newborn. Despite being over 30 years old, the practice of neonatology is as much of an art as a science. Advances in the basic science research have improved our understanding of use of pharmacologic agents in the premature and full-term neonate including drug disposition pathways. Expanding our knowledge on issues such as physiology of hematopoietic factors, the pharmacologic responses of conditions such as PDA and PPHN, and newer technologies for drug administration, as well as other pharmacologic responses in the neonate are vital in the development of safe and efficacious treatments for neonates. Many questions remain unanswered, and every clinician must make an effort to contribute to the knowledge and understanding of pharmacotherapy in this patient population.

Drug Treatment of Pulmonary Hypertension in Children

PubMed Central

Vorhies, Erika E; Ivy, David Dunbar

2013-01-01

Pulmonary arterial hypertension (PAH) is a rare disease in infants and children that is associated with significant morbidity and mortality. The disease is characterized by progressive pulmonary vascular functional and structural changes resulting in increased pulmonary vascular resistance and eventual right heart failure and death. In the majority of pediatric patients, PAH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Although treatment of the underlying disease and reversal of advanced structural changes has not yet been achieved with current therapy, quality of life and survival have been improved significantly. Targeted pulmonary vasodilator therapies, including endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors, have demonstrated hemodynamic and functional improvement in children. The management of pediatric PAH remains challenging as treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts. This article reviews the current drug therapies and their use in the management of PAH in children. PMID:24114695

Facilitating treatment entry among out-of-treatment injection drug users.

PubMed Central

Booth, R E; Kwiatkowski, C; Iguchi, M Y; Pinto, F; John, D

1998-01-01

OBJECTIVE: High risk injection practices are common among injecting drug users (IDUs), even following intervention efforts. Moreover, relapse to risk behaviors has been reported among those who initiate risk reduction. Substance abuse treatment offers the potential to reduce or eliminate injecting risk behaviors through drug cessation. We report on the effectiveness of two intervention strategies in facilitating treatment entry among out-of-treatment IDUs: motivational interviewing (MI), and intervention developed to help individuals resolve their ambivalence about behavior change, and free treatment for 90 days. These conditions were compared with an intervention focusing on a hierarchy of safer injecting practice, referred to here as risk reduction (RR), and no free treatment. METHODS: Nearly 200 out-of-treatment IDUs were randomly assigned to one of four experimental conditions: MI/free treatment, MI/no free treatment, RR/free treatment, and RR/no free treatment. Regardless of assignment, we assisted anyone desiring treatment by calling to schedule the appointment, providing transportation, and waiving the intake fee. RESULTS: Overall, 42% of study participants entered treatment. No significant differences were found between MI and RR; however, 52% of those assigned free treatment entered compare with 32% for those who had to pay. Other predictors of treatment entry included prior treatment experiences, perceived chance of contracting acquired immunodeficiency syndrome (AIDS) greater than 50%, "determination" stage of change, greater frequency of heroin injecting, and fewer drug-using friends. CONCLUSIONS: These findings support the importance of removing barriers to treatment entry. PMID:9722817

Recent Advances in Drug Eluting Stents

PubMed Central

Puranik, Amey S.; Dawson, Eileen R.; Peppas, Nicholas A.

2013-01-01

One of the most common medical interventions to reopen an occluded vessel is the implantation of a coronary stent. While this method of treatment is effective initially, restenosis, or the re-narrowing of the artery frequently occurs largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents were developed in order to provide local, site-specific, controlled release of drugs that can inhibit neointima formation. By implementing a controlled release delivery system it may be possible to control the time release of the pharmacological factors and thus be able to bypass some of the critical events associated with stent hyperplasia and prevent the need for subsequent intervention. However, since the advent of first-generation drug eluting stents, long-term adverse effects have raised concerns regarding their safety. These limitations in safety and efficacy have triggered considerable research in developing biodegradable stents and more potent drug delivery systems. In this review, we shed light on the current state-of-the-art in drug eluting stents, problems related to them and highlight some of the ongoing research in this area. PMID:23117022

Estimating drug treatment needs among state prison inmates.

PubMed

Belenko, Steven; Peugh, Jordon

2005-03-07

Growing prison populations in the U.S. are largely due to drug-related crime and drug abuse. Yet, relatively few inmates receive treatment, existing interventions tend to be short-term or non-clinical, and better methods are needed to match drug-involved inmates to level of care. Using data from the 1997 Survey of Inmates in State Correctional Facilities, a nationally representative sample of 14,285 inmates from 275 state prisons, we present a framework for estimating their levels of treatment need. The framework is drawn partly from the American Society of Addiction Medicine Patient Placement Criteria and other client matching protocols, incorporating drug use severity, drug-related behavioral consequences, and other social and health problems. The results indicate high levels of drug involvement, but considerable variation in severity/recency of use and health and social consequences. We estimate that one-third of male and half of female inmates need residential treatment, but that half of male and one-third of female inmates may need no treatment or short-term interventions. Treatment capacity in state prisons is quite inadequate relative to need, and improvements in assessment, treatment matching, and inmate incentives are needed to conserve scarce treatment resources and facilitate inmate access to different levels of care.

Vaccines against drugs of abuse: a viable treatment option?

PubMed

Kantak, Kathleen M

2003-01-01

Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically

28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...

28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...

28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...

28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...

28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...

Treatment Retention among African Americans in the Dane County Drug Treatment Court

ERIC Educational Resources Information Center

Brown, Randall T.; Zuelsdorff, Megan; Gassman, Michele

2009-01-01

Drug treatment courts (DTCs) provide substance abuse treatment and case management services to offenders with substance use disorders as an alternative to incarceration. Studies indicate that African Americans less frequently complete DTC programming. The current study analyzed data from the Dane County Drug Treatment Court (n = 573). The study…

Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents.

PubMed

Jha, Sheetal; Sharma, Pramod K; Malviya, Rishabha

2016-01-01

In this review article, authors reviewed about the liposomes which are amongst various drug delivering systems for the delivery of the therapeutic agents at the target site. Advances in liposomal drug delivery systems for the cancer therapy have enhanced the therapeutic levels of the anticancer moieties. Liposomes show promising action on the tumor by incorporating less amount of drug at the target site, with minimum toxic effect and maximum therapeutic effect and thereby enhancing the bioavailability. Liposome-based drug delivery systems provide the potential to elevate the effect of drug concentration in tumor cells. Manuscript briefly describes the role of liposomes in cancer therapy and various patents based on the same. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A look backward and forward in the regulatory and treatment history of multiple myeloma: Approval of novel-novel agents, new drug development, and longer patient survival.

PubMed

Kazandjian, Dickran; Landgren, Ola

2016-12-01

The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time. We aim to review and give further insight into drug development and novel drug approvals that have revolutionized the treatment of MM. Published by Elsevier Inc.

A phase II study tests a new drug for patients with advanced thyroid cancer | Center for Cancer Research

Cancer.gov

A phase II trial of CUDC-907, a new drug that may be able to shrink thyroid tumors that have spread or gotten worse, is being tested in metastatic or advanced thyroid cancer.  Currently, there is no standard or effective treatment for the most aggressive types of thyroid cancer such as anaplastic and poorly differentiated thyroid cancer.  Learn more...

Present and future treatment of advanced non-small cell lung cancer.

PubMed

Crinò, Lucio; Cappuzzo, Federico

2002-06-01

Platinum-based chemotherapy is considered the standard treatment for advanced non-small cell lung cancer (NSCLC). Several phase II trials using cisplatin in combination with new chemotherapeutic agents, such as gemcitabine, the taxanes, vinorelbine, and irinotecan, showed impressive response rates and suggested an improvement in overall survival. Large phase III trials comparing these second-generation cisplatin regimens indicated a substantial equivalence of new combinations, marginally improving the outcome of patients over the first-generation platinum-based regimens. Phase III trials have not yet shown dramatic advantages for either multiple-drug regimens, with nonoverlapping mechanisms of action and toxicity, or nonplatinum doublets, with efficacy and/or toxicity profiles superior to those of platinum-based chemotherapy. Chemotherapy in advanced non-small cell lung cancer has reached a plateau, and it is clear that new approaches are required. These should include prevention, screening, and early detection, and the use of novel treatments based on our understanding of the biology and molecular biology of this disease. Copyright 2002, Elsevier Science (USA). All rights reserved.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

PubMed

Sicherer, Scott H; Leung, Donald Y M

2006-07-01

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

Current treatment options and drug delivery systems as potential therapeutic agents for ovarian cancer: a review.

PubMed

Ye, Hongye; Karim, Anis Abdul; Loh, Xian Jun

2014-12-01

Ovarian cancer is one of the most common and deadliest gynecologic cancer with about 75% of the patients presenting in advanced stages. The introduction of intraperitoneal chemotherapy in 2006 had led to a 16 month improvement in the overall survival. However, catheter-related complication and the complexity of the procedure had deterred intraperitoneal route as the preferred route of treatment. Other alternative treatments had been developed by incorporating other FDA-approved agents or procedures such as pegylated liposomal doxorubicin (PLD), hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and the administration of bevacizumab. Various clinical trials were conducted on these alternatives as both the first-line treatment and second- or third-line therapy for the recurrent disease. The outcome of these studies were summarized and discussed. A prospective improvement in the treatment of ovarian cancer could be done through the use of a drug delivery system. Selected promising recent developments in ovarian cancer drug delivery systems using different delivery vehicles, surface modifications, materials and drugs were also reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer

PubMed Central

Nelson, Michael H; Dolder, Christian R

2007-01-01

Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10–1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated. PMID:18472989

Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

PubMed Central

Macklin, Ruth; Cowan, Ethan

2013-01-01

Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID:22778343

THE EFFECTIVENESS OF COMPULSORY DRUG TREATMENT: A SYSTEMATIC REVIEW

PubMed Central

Werb, D; Kamarulzaman, A; Meacham, MC; Rafful, C; Fisher, B; Strathdee, SA; Wood, E

2016-01-01

Background Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. Methods We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Results Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e. 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. Conclusion There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human

Emerging drugs for the treatment of obesity.

PubMed

Martinussen, Christoffer; Bojsen-Moller, Kirstine Nyvold; Svane, Maria Saur; Dejgaard, Thomas Fremming; Madsbad, Sten

2017-03-01

The increasing prevalence of obesity represents a huge threat to public health and the current pharmacological treatment options are limited. Bariatric surgery is by far the most effective treatment for severe obesity, highlighting the urgent need for new and improved drug therapies. Areas covered: Based on the physiological regulation of energy homeostasis, pharmacological strategies to treat obesity are evaluated with focus on drugs in phase 2 and 3 clinical development. The potential impact of these drugs on current treatment standards and the barriers for development are discussed and set in a historical perspective of previous antiobesity medications. Expert opinion: The radical effects of bariatric surgery have extended our understanding of the mechanisms controlling appetite and boosted the search for new drug targets in obesity treatment. Accordingly, several compounds targeting the central nervous system and/or periphery are in pipeline for obesity. These drugs should be evaluated over a wide array of end-points; in particular, long-term safety monitoring is necessary as serious adverse events may appear. Combination therapy targeting more than one pathway controlling energy balance might be necessary to achieve substantial weight loss while minimising side effects.

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories – indications for novel treatments of addiction*

PubMed Central

Everitt, Barry J

2014-01-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus–response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. PMID:24935353

Evaluation of advanced wastewater treatment systems for water reuse in the era of advanced wastewater treatment

NASA Astrophysics Data System (ADS)

Kon, Hisao; Watanabe, Masahiro

This study focuses on effluent COD concentration from wastewater treatment in regards to the reduction of pathogenic bacteria and trace substances in public waters. The main types of secondary wastewater treatment were conventional activated sludge processes. Recently, however, advance wastewater treatment processes have been developed aimed at the removal of nitrogen and phosphorus, and the effluent quality of these processes was analyzed in this study. Treatment processes for water reclamation that make effluent to meet the target water quality for reuse purposes were selected and also optimum design parameters for these processes were proposed. It was found that the treatment cost to water reclamation was greatly affected by the effluent COD of the secondary treatment. It is important to maintain low COD concentration in the secondary treated effluent. Therefore, it is considered that adequate cost benefits would be obtained by achieving target COD quality through shifting from a conventional activated sludge process to an advanced treatment process.

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy?

PubMed Central

Kateb, Babak; Chiu, Katherine; Black, Keith L.; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F.; Farahani, Keyvan; Okun, Michael S.; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.

2012-01-01

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1–100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law–healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?

PubMed

Kateb, Babak; Chiu, Katherine; Black, Keith L; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F; Farahani, Keyvan; Okun, Michael S; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D

2011-01-01

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories--indications for novel treatments of addiction.

PubMed

Everitt, Barry J

2014-07-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus-response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. © 2014 The Author. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

PubMed

Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

2015-07-01

Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Drug addicts treatment motivations: perception of family members.

PubMed

Ferreira, Aline Cristina Zerwes; Capistrano, Fernanda Carolina; de Souza, Edice Bueno; Borba, Letícia de Oliveira; Kalinke, Luciana Puchalski; Maftum, Mariluci Alves

2015-01-01

to identify the reasons and motivations why family members search treatment for the drug addicted. descriptive qualitative research, developed in 2012 and 2013, in a Drug Addicts Rehabilitation Unit of Parana State, Brazil. A total of 19 semi-structured interviews were conducted with the drug addicts' family members in treatment. The results were analyzed based on the Transtheoretical Model of Behavior Change and organized in thematic categories according with qualitative data analysis. the search for treatment for drug addicts occurred: in the pre-contemplation stage influenced by external factors; in the contemplation stage both for ambivalence and behavioral changes needs; in the action stage by awareness of drug addiction and also professional help needs; and in the maintenance stage because of the non-conservation of behavioral changes. an evaluation of motivational stages in the beginning of treatment is required for expansion of success possibilities in the rehabilitation process.

Sexual dysfunction in 2013: Advances in epidemiology, diagnosis and treatment.

PubMed

Lee, King Chien Joe; Fahmy, Nader; Brock, Gerald B

2013-09-01

To provide a contemporary review of the epidemiology, diagnosis and treatment of premature ejaculation (PE) and erectile dysfunction (ED). We searched for English-language articles published in the past 12 months using the PubMed database. Relevant articles on the subjects of sexual dysfunction, ED and PE were selected for review. Recent studies on male sexual dysfunction have provided new therapeutic possibilities. Tramadol, a well-used analgesic, has a new role in the treatment of PE. Super-selective targeting of dorsal penile nerves by surgery or cryoablative technologies might become a viable treatment option for refractory PE in the future. The role of ED as a harbinger of important comorbidities allows for the early detection and intervention of these conditions, which can optimise therapeutic outcomes. The long-term effect of chronic phosphodiesterase-5 inhibitors on endothelial dysfunction, the angiogenic potential of low-intensity extracorporeal shock wave therapy, and further advances in drug-eluting endovascular stents might in future allow clinicians to treat ED more definitively.

Beyond Standard Therapy: Drugs Under Investigation for The Treatment of Gastrointestinal Stromal Tumor

PubMed Central

Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K

2015-01-01

Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival. PMID:26098203

Clinical roundtable monograph: new and emerging treatments for advanced prostate cancer.

PubMed

George, Daniel J; Kantoff, Philip W; Lin, Daniel W

2011-06-01

Historically, the treatment of metastatic castration-resistant prostate cancer (CRPC) has been limited to chemotherapeutic regimens that did not improve patient survival. In 2004, clinical studies began to demonstrate significant improvements in patient outcomes, including overall survival, with docetaxel versus mitoxantrone chemotherapy. Since these pivotal trials, the combination of docetaxel plus prednisone has become a standard of care for patients with metastatic CRPC. However, the limited survival benefit achieved with this regimen prompted several investigations into the development of alternative therapeutic options. Recent advances have now led to an unprecedented number of new drug approvals within the past year, providing many new treatment options for patients with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer treatment, is the first such immunotherapeutic agent approved by the US Food and Drug Administration. Other successes include abiraterone acetate, the first androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor, both of which have demonstrated improved survival following docetaxel failure. The bone-targeting agent denosumab, also recently approved in this setting, offers these patients significant improvement in the prevention of skeletal-related events. The data supporting the approval of each of these agents are described in this monograph, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies. The experts also discuss several of the issues regarding the introduction of these novel agents into clinical practice for metastatic CRPC patients.

Polymeric drugs: Advances in the development of pharmacologically active polymers

PubMed Central

Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

2015-01-01

Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

Managing la malilla: Exploring drug treatment experiences among injection drug users in Tijuana, Mexico, and their implications for drug law reform

PubMed Central

Syvertsen, Jennifer; Pollini, Robin A.; Lozada, Remedios; Vera, Alicia; Rangel, Gudelia; Strathdee, Steffanie A.

2012-01-01

Background In August 2009, Mexico reformed its drug laws and decriminalized small quantities of drugs for personal use; offenders caught three times will be mandated to enter drug treatment. However, little is known about the quality or effectiveness of drug treatment programs in Mexico. We examined injection drug users’ (IDUs) experiences in drug treatment in Tijuana, Mexico, with the goal of informing program planning and policy. Methods We examined qualitative and quantitative data from Proyecto El Cuete, a multi-phased research study on HIV risk among IDUs in Tijuana. Phase I consisted of 20 in-depth interviews and Phase II employed respondent-driven sampling to recruit 222 IDUs for a quantitative survey. We also reviewed national drug policy documents, surveillance data, and media reports to situate drug users’ experiences within the broader sociopolitical context. Results Participants in the qualitative study were 50% male with a mean age of 32; most injected heroin (85.0%) and methamphetamine (60.0%). The quantitative sample was 91.4% male with a mean age of 35; 98.2% injected heroin and 83.7% injected heroin and methamphetamine together. The majority of participants reported receiving treatment: residential treatment was most common, followed by methadone; other types of services were infrequently reported. Participants’ perceptions of program acceptability and effectiveness were mixed. Mistreatment emerged as a theme in the qualitative interviews and was reported by 21.6% of Phase II participants, primarily physical (72.0%) and verbal (52.0%) abuse. Conclusions Our results point to the need for political, economic, and social investment in the drug treatment system before offenders are sentenced to treatment under the revised national drug law. Resources are needed to strengthen program quality and ensure accountability. The public health impact of the new legislation that attempts to bring drug treatment to the forefront of national drug policy

Advances in treatment of obstructive sleep apnea syndrome.

PubMed

Collop, Nancy A

2009-09-01

The treatments for obstructive sleep apnea (OSA) described in this paper represent the latest information and data. Nasal continuous positive airway pressure, initially described in 1981, remains the cornerstone of therapy. Advances in mask interfaces, the use of humidification, the downloading of usage information, the development of pressure delivery modifications, and reductions in the size and noise of the machines have improved the devices over the past decade. Nevertheless, the basic premise of positive pressure delivery to splint the airway remains the primary driver of efficacy. Surgery for OSA, other than tracheostomy, has also been used for about the same period (uvulopalatopharyngoplasty was also initially described in 1981), but its efficacy has probably improved only marginally. The advances in surgical techniques have come through improved patient selection, minimally invasive techniques, and the performance of outcome studies. Surgery clearly remains a second-line or third-line therapy for moderate to severe OSA. Dental appliances were also introduced over two decades ago and clearly have become more mainstream in our treatment approach to OSA. Dental appliances are now considered a reasonable first-line therapy for mild OSA and perhaps even for some patients with moderate OSA. Custom-made appliances are clearly superior to those that cannot be adjusted, and in the hands of an experienced dentist or similarly trained expert, they are moderately successful for most patients. Among the newer therapies, transnasal insufflation and nasal expiratory resistance clearly have promise, again for patients with mild to moderate OSA. Further study may determine who will benefit from such modalities. No medications have been shown to have clinically significant efficacy, and drug treatment remains adjunctive.

Repositioning approved drugs for the treatment of problematic cancers using a screening approach

PubMed Central

Kuttler, Fabien; Banfi, Damiano; Turcatti, Gerardo; Dyson, Paul J.

2017-01-01

Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over the last four decades. Nevertheless, despite the growing number of new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it is important to ensure that existing drugs used to treat other types of cancers, and potentially other diseases, are not overlooked when searching for new chemotherapy regimens for these problematic cancer types. We describe a screening approach that identifies chemotherapeutics for the treatment of lung and pancreatic cancers, based on drugs already approved for other applications. Initially, the 1280 chemically and pharmacologically diverse compounds from the Prestwick Chemical Library® (PCL) were screened against A549 (lung cancer) and PANC-1 (pancreatic carcinoma) cells using the PrestoBlue fluorescent-based cell viability assay. More than 100 compounds from the PCL were identified as hits in one or both cell lines (80 of them, being drugs used to treat diseases other than cancer). Selected PCL hits were further evaluated in a dose-response manner. Promising candidates for repositioning emanating from this study include antiparasitics, cardiac glycosides, as well as the anticancer drugs vorinostat and topotecan. PMID:28166232

The drug treatment of delayed ejaculation

PubMed Central

Elsaied, Moustafa A.; Mostafa, Taymour

2016-01-01

Delayed ejaculation (DE) is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we reviewed how DE is treated pharmacologically .We also highlighted specific settings where drugs could be introduced to medical practice. Electronic databases were searched from 1966 to February 2016, including PubMed MEDLINE, EMBASE, EBCSO Academic Search Complete, Cochrane Systematic Reviews Database, and Google Scholar using key words; delayed ejaculation, retarded ejaculation, inhibited ejaculation, drugs, treatment, or pharmacology. To achieve the maximum sensitivity of the search strategy and to identify all studies, we combined “delayed ejaculation” as Medical Subject Headings (MeSH) terms or keywords with each of “testosterone” or “cabergoline” or “bupropion” or “amantadine” or “cyproheptadine” or “midodrine” or “imipramine” or “ephedrine” or “pseudoephedrine” or “yohimbine” or “buspirone” or “oxytocin” or “bethanechol” as MeSH terms or keywords. There are a number of drugs to treat patients with DE including: testosterone, cabergoline, bupropion, amantadine, cyproheptadine, midodrine, imipramine, ephedrine, pseudoephedrine, yohimbine, buspirone, oxytocin, and bethanechol. Although there are many pharmacological treatment options, the evidence is still limited to small trials, case series or case reports. Review of literature showed that evidence level 1 (Double blind randomized clinical trial) studies were performed with testosterone, oxytocin, buspirone or bethanechol treatment. It is concluded that successful drug treatment of DE is still in its infancy. The clinicians need to be aware of the pathogenesis of DE and the pharmacological basis underlying the use of different drugs to extend better care for these patients. Various drugs are available to address such problem, however their evidence of efficacy is still limited and their

[Vaccines for the treatment of drug addiction].

PubMed

Zorzoli, Ermanno; Marino, Maria Giulia; Bagnato, Barbara; Franco, Elisabetta

2016-01-01

The treatment of drug addiction is a very wide-ranging sector within modern medicine. The use of immunotherapy in this context represents an innovative approach. The purpose of this paper is to illustrate, through a literature review, the main avenues of research and the results obtained with immunotherapy in the treatment of drug addiction.

Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

PubMed Central

Fecher, Leslie A; Sharfman, William H

2015-01-01

Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

A Comparative Study of the Attitudes of College Students and Drug Treatment Center Residents Toward Drugs, Other Drug Users and Themselves.

ERIC Educational Resources Information Center

Page, Richard C.; Mitchell, Sam

1986-01-01

Assessed the attitudes of college students and drug treatment center residents with histories of using marijuana and amphetamines. The drug treatment center residents tended to devalue themselves, drugs, and peers in the drug culture to a greater extent than the students. (Author/BL)

Drug Discovery and Development of Antimalarial Agents: Recent Advances.

PubMed

Thota, Sreekanth; Yerra, Rajeshwar

2016-01-01

Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.

Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

PubMed Central

2016-01-01

Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases. PMID:27867663

Insoluble drug delivery strategies: review of recent advances and business prospects

PubMed Central

Kalepu, Sandeep; Nekkanti, Vijaykumar

2015-01-01

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects. PMID:26579474

Recent advances in diagnosis and treatment of chronic myeloproliferative neoplasms

PubMed Central

Guglielmelli, Paola

2010-01-01

The Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) have recently been the focus of tremendous advances in basic knowledge of disease pathophysiology following the recognition of mutations in JAK2 and MPL. These discoveries also led to refinement of the criteria employed for diagnosis. The prognostic roles of the JAK2 V617F mutation and of leukocytosis as independent risk factors for thrombosis, which represents the leading cause of death in patients with polycythemia vera and essential thrombocythemia, are supported by retrospective studies. A new risk stratification approach to the patient with primary myelofibrosis allows clinicians to distinguish categories of patients with significantly different expected survival. Finally, new drugs are currently being tested for MPNs, and molecular discoveries could ultimately lead to the development of a specific targeted therapy. Overall, significant advances in diagnosis, prognostication, and treatment have taken place in the last couple of years in the field of MPNs. PMID:20948870

Economic Analysis of First-Line Treatment with Erlotinib in an EGFR-Mutated Population with Advanced NSCLC.

PubMed

Vergnenegre, Alain; Massuti, Bartomeu; de Marinis, Filippo; Carcereny, Enric; Felip, Enriqueta; Do, Pascal; Sanchez, Jose Miguel; Paz-Arez, Luis; Chouaid, Christos; Rosell, Rafael

2016-06-01

The cost-effectiveness of first-line tyrosine kinase inhibitor therapy in epidermal growth factor receptor gene (EGFR)-mutated advanced-stage non-small cell lung cancer (NSCLC) is poorly documented. We therefore conducted a cost-effectiveness analysis of first-line treatment with erlotinib versus standard chemotherapy in European patients with advanced-stage EGFR-mutated NSCLC who were enrolled in the European Erlotinib versus Chemotherapy trial. The European Erlotinib versus Chemotherapy study was a multicenter, open-label, randomized phase III trial performed mainly in Spain, France, and Italy. We based our economic analysis on clinical data and data on resource consumption (drugs, drug administration, adverse events, and second-line treatments) collected during this trial. Utility values were derived from the literature. Incremental cost-effectiveness ratios were calculated for the first-line treatment phase and for the overall strategy from the perspective of the three participating countries. Sensitivity analyses were performed by selecting the main cost drivers. Compared with standard first-line chemotherapy, the first-line treatment with erlotinib was cost saving (€7807, €17,311, and €19,364 for Spain, Italy and France, respectively) and yielded a gain of 0.117 quality-adjusted life-years. A probabilistic sensitivity analysis indicated that, given a willingness to pay at least €90,000 for 1 quality-adjusted life-year, the probability that a strategy of first-line erlotinib would be cost-effective was 100% in France, 100% in Italy, and 99.8% in Spain. This economic analysis shows that first-line treatment with erlotinib, versus standard chemotherapy, is a dominant strategy for EGFR-mutated advanced-stage NSCLC in three European countries. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.

PubMed

Polireddy, Kishore; Chen, Qi

2016-01-01

Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer.

Drugs in Mental Retardation: Treatment or Tragedy?

ERIC Educational Resources Information Center

Aman, Michael G.

1985-01-01

Treatment of mentally retarded persons with psychotropic and anticonvulsant drugs is discussed in terms of drug classification, rationale for use, attitudes toward use, and clinical research findings. The literature on neuroleptic, anticonvulsant, anxiolytic, and cerebral stimulant drugs is summarized. Controversial reports that some medications…

Large-scale extraction of accurate drug-disease treatment pairs from biomedical literature for drug repurposing

PubMed Central

2013-01-01

Background A large-scale, highly accurate, machine-understandable drug-disease treatment relationship knowledge base is important for computational approaches to drug repurposing. The large body of published biomedical research articles and clinical case reports available on MEDLINE is a rich source of FDA-approved drug-disease indication as well as drug-repurposing knowledge that is crucial for applying FDA-approved drugs for new diseases. However, much of this information is buried in free text and not captured in any existing databases. The goal of this study is to extract a large number of accurate drug-disease treatment pairs from published literature. Results In this study, we developed a simple but highly accurate pattern-learning approach to extract treatment-specific drug-disease pairs from 20 million biomedical abstracts available on MEDLINE. We extracted a total of 34,305 unique drug-disease treatment pairs, the majority of which are not included in existing structured databases. Our algorithm achieved a precision of 0.904 and a recall of 0.131 in extracting all pairs, and a precision of 0.904 and a recall of 0.842 in extracting frequent pairs. In addition, we have shown that the extracted pairs strongly correlate with both drug target genes and therapeutic classes, therefore may have high potential in drug discovery. Conclusions We demonstrated that our simple pattern-learning relationship extraction algorithm is able to accurately extract many drug-disease pairs from the free text of biomedical literature that are not captured in structured databases. The large-scale, accurate, machine-understandable drug-disease treatment knowledge base that is resultant of our study, in combination with pairs from structured databases, will have high potential in computational drug repurposing tasks. PMID:23742147

Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

PubMed Central

Smith, J. Joshua; Garcia-Aguilar, Julio

2015-01-01

Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

Antibodies and antibody-drug conjugates in the treatment of Hodgkin lymphoma.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2014-07-01

Hodgkin lymphoma (HL) is a B cell-derived lymphoid malignancy most often affecting young adults. More than 80% of HL patients achieve long-term remission after appropriate first-line treatment consisting of multiagent chemotherapy and/or radiotherapy (RT). In addition, approximately 50% of patients with disease recurrence remain relapse-free after salvage therapy with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). However, patients with multiple relapses are mostly in a palliative situation, and novel drugs for this patient group are needed. Furthermore, novel less toxic but equally effective first-line and second-line approaches are required as therapy-related late sequelae represent a relevant cause of morbidity and mortality in HL survivors. Several antibodies and antibody-drug conjugates (ADC) targeting CD30 and CD20 have recently been evaluated in HL. Excellent response rates in heavily pretreated patients were observed with the ADC brentuximab vedotin directed against CD30. Thus, ongoing trials investigate brentuximab vedotin in different additional indications. One example is the first-line treatment of advanced HL where the drug is currently being evaluated in combination with variants of the first-line protocols ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). Anti-CD20 antibodies given either as single agent or in combination with conventional chemotherapy have also been investigated and still undergo investigation in prospective studies including HL patients. This article reviews the available data on treatment approaches including antibodies and ADC in HL patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

PubMed

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

[Outcomes of treatment of chemotherapy drugs different manufacturers tuberculosis patients with multiple drug resistance].

PubMed

2014-09-01

The article is devoted to studying the effectiveness of treatment of tuberculosis (TB) patients with multidrug-resistant TB drugs 2 number of different manufacturers. To assess the effectiveness of treatment of second-line drugs were taken to study two groups of patients: Group 1 - 164 patients who received anti-TB drugs from the Global Fund and Group 2 174 patients who received anti-TB drugs for the national program. Comparative evaluation showed high efficiency second-line drugs from the Global Fund, as evidenced by the high level of 95,8 % abacillation in a short time in this patient group.

Treatment as Part of Drug Court: The Impact on Graduation Rates

ERIC Educational Resources Information Center

Taxman, Faye S.; Bouffard, Jeffrey A.

2005-01-01

Drug treatment is one of the critical components of drug court programming, yet it has not been thoroughly studied in the drug court literature. Very little is understood about the nature of drug treatment services provided in the drug court setting. The purpose of this study was to examine the effects of selected treatment variables on drug court…

A discrete choice model of drug abuse treatment location.

PubMed Central

Goodman, A C; Nishiura, E; Hankin, J R

1998-01-01

OBJECTIVE: To identify short-term drug abuse treatment location risk factors for ten large, self-insured firms starting January 1, 1989 and ending December 31, 1991. DATA SOURCES/STUDY SETTING: Study population selected from a large database of health insurance claims for all treatment events starting January 1, 1989 and ending December 31, 1991. STUDY DESIGN: A nested binomial logit method is used to estimate firm-specific patterns of treatment location. The differences in treatment location patterns among firms are then decomposed into firm effects (holding explanatory variables constant among firms) and variable effects (holding firm-specific parameters constant). PRINCIPAL FINDINGS: Probability of inpatient drug treatment is directly related to the type of drug diagnosis. The most important factors are diagnoses of drug dependence (versus drug abuse) and/or a cocaine dependence. Firm-specific factors also make a substantive difference. Controlling for patient risk factors, firm-specific probabilities of inpatient treatment vary by as much as 87 percent. Controlling for practices of firms and their insurance carriers, differing patient risk profiles cause probabilities of inpatient treatment to vary by as much as 69 percent among firms. Use of the outpatient setting increased over the three-year period. CONCLUSIONS: There are two plausible explanations for the findings. First, people beginning treatment later in the three-year period had less severe conditions than earlier cases and therefore had less need of inpatient treatment. Second, drug abuse treatment experienced the same trend toward the increased use of outpatient care that characterized treatment for other illnesses in the 1980s and early 1990s. PMID:9566181

A Review on Advanced Treatment of Pharmaceutical Wastewater

NASA Astrophysics Data System (ADS)

Guo, Y.; Qi, P. S.; Liu, Y. Z.

2017-05-01

The composition of pharmaceutical wastewater is complex, which is high concentration of organic matter, microbial toxicity, high salt, and difficult to biodegrade. After secondary treatment, there are still trace amounts of suspended solids and dissolved organic matter. To improve the quality of pharmaceutical wastewater effluent, advanced treatment is essential. In this paper, the classification of the pharmaceutical technology was introduced, and the characteristics of pharmaceutical wastewater effluent quality were summarized. The methods of advanced treatment of pharmaceutical wastewater were reviewed afterwards, which included coagulation and sedimentation, flotation, activated carbon adsorption, membrane separation, advanced oxidation processes, membrane separation and biological treatment. Meanwhile, the characteristics of each process were described.

Recent advances in immunosensor for narcotic drug detection

PubMed Central

Gandhi, Sonu; Suman, Pankaj; Kumar, Ashok; Sharma, Prince; Capalash, Neena; Suri, C. Raman

2015-01-01

Introduction: Immunosensor for illicit drugs have gained immense interest and have found several applications for drug abuse monitoring. This technology has offered a low cost detection of narcotics; thereby, providing a confirmatory platform to compliment the existing analytical methods. Methods: In this minireview, we define the basic concept of transducer for immunosensor development that utilizes antibodies and low molecular mass hapten (opiate) molecules. Results: This article emphasizes on recent advances in immunoanalytical techniques for monitoring of opiate drugs. Our results demonstrate that high quality antibodies can be used for immunosensor development against target analyte with greater sensitivity, specificity and precision than other available analytical methods. Conclusion: In this review we highlight the fundamentals of different transducer technologies and its applications for immunosensor development currently being developed in our laboratory using rapid screening via immunochromatographic kit, label free optical detection via enzyme, fluorescence, gold nanoparticles and carbon nanotubes based immunosensing for sensitive and specific monitoring of opiates. PMID:26929925

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs - provision of due diligence in the treatment process.

PubMed

Zajdel, Justyna; Zajdel, Radosław

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

Diagnosis and Treatment of Drug-Resistant Tuberculosis.

PubMed

Caminero, José A; Cayla, Joan A; García-García, José-María; García-Pérez, Francisco J; Palacios, Juan J; Ruiz-Manzano, Juan

2017-09-01

In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Emerging Drugs for the Treatment of Breast Cancer Brain Metastasis: A Review of Patent Literature.

PubMed

Anaya-Ruiz, Maricruz; Bandala, Cindy; Martinez-Morales, Patricia; Landeta, Gerardo; Martinez-Contreras, Rebeca D; Martinez-Montiel, Nancy; Perez-Santos, Martin

2018-04-29

Despite dramatic advances in cancer treatment that lead to long-term survival, there is an increasing number of patients presenting with clinical manifestations of cerebral metastasis in breast cancer, for whom only palliative treatment options exist. The present review aims to provide to identify recent patens of breast cancer brain metastasis that may have application in improving cancer treatment. Recent patents regarding the breast cancer brain metastasis were obtained from USPTO patent databases, Esp@cenet, Patentscope and Patent Inspiration®. A total of 55 patent documents and 35 drug targets were recovered. Of these, a total of 45 patents and 10 patents were biotech drugs and chemical drugs, respectively. Among the target drugs analyzed were neurotrophin-3, protocadherin 7, CXCR4, PTEN, GABA receptor 3, L1CAM, PI3K-Akt / mTOR, VEGFR2, Claudin-5, Occludin, and NKG2A, among others. In this study we found 35 drug targets for metastasis to the brain in breast cancer, with 60% of them including only one patent, which establishes that this area of research is very recent, and that these targets have recently been linked to metastasis to the brain. On the other hand, 19 drug targets, among them VEGF, VEGFR2, CXCL12, and CXCR4, have been addressed for the first time until 6 years ago, confirming that the development of drugs for brain metastasis in breast cancer is an incipient area, but with interesting potential. Interestingly, the stage of inside the brain, was the stage with the lowest amount of drug targets, which places it as a priority for research and drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Current status and future prospect of internal medicine treatment for advanced esophageal cancer].

PubMed

Wang, F; Fan, Q X

2016-09-23

Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research. Molecular targeted drugs have become a new developmental direction in cancer treatment because of their high specificity and antitumor activity, but the effects on esophageal cancer remain controversial. With the development of immune check point blockade treatment, breakthrough has been made in tumor immunotherapy, which has become an important means in cancer comprehensive treatment and shown a good prospect of treatment.

Correlates of injection drug use among individuals admitted to public and private drug treatment facilities in Turkey.

PubMed

Mutlu, Elif; Alaei, Arash; Tracy, Melissa; Waye, Katherine; Cetin, Mustafa Kemal; Alaei, Kamiar

2016-07-01

The number of individuals seeking treatment for drug use has been increasing in recent years in Turkey. However, existing research on patterns and risk factors for drug use and how they vary by age and location in Turkey is limited. We examined the socio-demographic characteristics, drug use behaviors, and treatment history of citizens admitted to inpatient substance use treatment at public and private facilities in Turkey during 2012 and 2013 and identified correlates of lifetime and current injection drug use. Of the 11,247 patients at the 22 public treatment centers in 2012-2013, a majority were male, lived with family, were unemployed, and had an average age of 27 years. Within private clinics (n=663), a higher proportion was female (9.7% private vs. 5.7% public), aged 11-17 years old (13% vs. 7.4%), used cannabis as their primary drug (18.4% vs. 13.2%), and had previously received drug treatment (57% vs. 47.2%). Within public centers, 40.4% reported ever injecting drugs and 33.7% reported injecting in the past 30 days; the corresponding percentages at private clinics were 22.5% and 18.1%. Significant predictors of injection drug use included being homeless, being a temporal employee or unemployed, having higher education, heroin as a preferred drug, having a longer duration of drug use, and prior drug treatment. Prevention and intervention efforts are needed to reduce the transition to heroin and injection drug use among youth as well as improve access to a variety of drug treatment options for people who use substances in Turkey. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advances in Lymphatic Imaging and Drug Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.

2011-09-10

Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastlymore » improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.« less

Effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer.

PubMed

Chen, Yan-zhi; Li, Zhan-dong; Gao, Fei; Zhang, Ying; Sun, Hong; Li, Ping-ping

2009-12-01

To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer (NSCLC). Sixty-three patients with stage III B and IV NSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table, with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin (NP) chemotherapy, but to the treatment group the Chinese drugs Shengmai Injection () by intravenous dripping and Gujin Granule () by oral intake were given additionally. The main observation indexes were response rate (RR), median survival time, 1-year survival rate and median time to progression (TTP); secondary observation indexes were side effects and cycles of chemotherapy. Altogether, 61 patients (33 from the treatment group and 28 from the control group) completed the observation and were assessable. RR was 48.5% (16/33) in the treatment group and 32.2% (9/28) in the control group, and the median survival time were 13 months and 9 months, respectively; the difference between the two groups was significant (P=0.0373 and P=0.014 respectively). However, the differences between groups were insignificant in terms of 1-year survival rate [51.5% (17/33) vs 46.4% (13/28), P=0.4042], median TTP (5.95 months vs 4.64 months, P=0.3242), grade III or IV bone marrow inhibition occurrence rate [33.3% (11/33) vs 39.3% (11/28), P=0.3500], and mean cycles of chemotherapy applied (2.94+/-0.94 cycles vs 2.75+/-0.75 cycles, P=0.4100). Combined Chinese drugs and chemotherapy can enhance the short-term therapeutic efficacy in the treatment of NSCLC and prolong patients' median survival time, but show no evident impact on TTP.

Enhancing Residential Treatment for Drug Court Participants

ERIC Educational Resources Information Center

Koob, Jeff; Brocato, Jo; Kleinpeter, Christine

2011-01-01

In this study, the authors describe and evaluate the impact of increased access to residential treatment added to traditional drug court services in Orange County, California, with a goal of increasing program retention, successful completion, and graduation rates for a high-risk drug offender population participating in drug court between January…

Evaluation of Drug Abuse Treatment Effectiveness: Summary of the DARP Followup Research. Treatment Research Report.

ERIC Educational Resources Information Center

Simpson, D. Dwayne; Sells, S. B.

The Drug Abuse Reporting Program (DARP) was initiated in 1969 as a federally supported client reporting system for community-based drug abuse treatment programs. Posttreatment follow-up interviews were conducted with over 4,000 persons from 34 treatment agencies to describe major findings from the drug abuse treatment research of the DARP relating…

Predictors of therapeutic engagement in prison-based drug treatment.

PubMed

Welsh, Wayne N; McGrain, Patrick N

2008-08-01

Few studies to date have examined predictors of therapeutic engagement (TE) or other indicators of responsiveness to prison drug treatment. Subjects were 347 inmates participating in a 12-month modified therapeutic community (TC) drug treatment program at a specialized treatment prison for convicted, drug-involved offenders. Data were obtained through correctional databases and the administration of the TCU Drug Screen II, the Resident Evaluation of Self and Treatment (REST), and the Counselor Rating of Client (CRC) form. Three main hypotheses were supported: (1) baseline motivation predicted therapeutic engagement net of other inmate characteristics; (2) critical dimensions of the treatment experience (e.g., peer support, counselor rapport) also predicted therapeutic engagement; and (3) dynamic predictors and programmatic characteristics became more important over time. Implications for research, theory and policy are discussed.

Are drug treatment services only for 'thieving junkie scumbags'? Drug users and the management of stigmatised identities.

PubMed

Radcliffe, Polly; Stevens, Alex

2008-10-01

This article uses qualitative interviews with 53 problematic drug users who had dropped out of treatment in England, UK to explore how they describe the stigmatisation of drug users and drug services. It discusses the construction of the category of the junkie through its association with un-controlled heroin use and criminality. It shows how some drug users carefully manage information about their discreditable identities by excluding themselves from this category, while acknowledging its validity for other drug users. The junkie identity was generally seen as shameful and therefore to be avoided, although it holds attractions for some drug users. For many of the interviewees, entry to treatment risked exposing their own activities as shaming, as they saw treatment as being a place that was populated by junkies and where it becomes more difficult to manage discreditable information. The treatment regime, e.g. the routine of supervised consumption of methadone, was itself seen by some as stigmatising and was also seen as hindering progress to the desired 'normal' life of conventional employment. Participation in the community of users of both drugs and drug services was perceived as potentially damaging to the prospects of recovery. This emphasises the importance of social capital, including links to people and opportunities outside the drug market. It also highlights the danger that using the criminal justice system to concentrate prolific offenders in treatment may have the perverse effects of excluding other people who have drug problems and of prolonging the performance of the junkie identity within treatment services. It is concluded that treatment agencies should address these issues, including through the provision of more drug services in mainstream settings, in order to ensure that drug services are not seen to be suitable only for one particularly stigmatised category of drug user.

A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

PubMed

Naidoo, Anushka; Naidoo, Kogieleum; McIlleron, Helen; Essack, Sabiha; Padayatchi, Nesri

2017-11-01

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens. © 2017, The American College of Clinical Pharmacology.

The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

PubMed

Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

2014-11-01

Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

The Therapeutic Workplace to Promote Treatment Engagement and Drug Abstinence in Out-of-Treatment Injection Drug Users: A Randomized Controlled Trial

PubMed Central

Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Leoutsakos, Jeannie-Marie S.; Silverman, Kenneth

2014-01-01

Objective Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. Method This study was conducted from 2008–2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement, and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Results Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). Conclusion The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. PMID:24607365

Advanced wastewater treatment simplified through research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souther, R.H.

A waste water treatment plant was built based on results of a small-scale pilot plant study, conducted largely in a search for efficiency as well as economy. Results were that 98 percent carbonaceous BOD (BOD/sub C/) and nitrogenous BOD (BOD/sub N/) were removed in a simplified, low-cost, single-stage advanced treatment process surpassing even some of the most sophisticated advanced complex waste treatment methods. The single-stage process treats domestic waste alone or combined with very high amounts of textile, electroplating, chemical, food, and other processing industrial wastewater. The process removed 100 percent of the sulfides above 98 percent of NH/sub 3/-N,more » over 90 percent of COD and phenols; chromium was converted from highly toxic hexavalent CrVI to nearly nontoxic trivalent chrome (CrIII). A pH up to 12 may be tolerated if no free hydroxyl (OH) ions are present. Equalization ponds, primary settling tanks, trickling filters, extra nitrogen removal tanks, carbon columns, and chemical treatment are not required. Color removal is excellent with clear effluent suitable for recycling after chlorination to water supply lakes. The construction cost of the single-stage advanced treatment plant is surprisingly low, about /sup 1///sub 2/ to /sup 1///sub 6/ as much as most conventional ineffective complex plants. This simplified, innovative process developed in independent research at Guilford College is considered by some a breakthrough in waste treatment efficiency and economy. (MU)« less

Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

PubMed

de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F

2004-09-14

Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

Introduction to the College on Problems of Drug Dependence special issue: contemporary advances in opioid neuropharmacology.

PubMed

Walsh, Sharon L; Unterwald, Ellen M; Izenwasser, Sari

2010-05-01

Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

Motivating the Drug Addict in Treatment

ERIC Educational Resources Information Center

St. Pierre, C. Andre

1971-01-01

Experience with numbers of drug addicts has shown them to be singularly unmotivated to discontinue drug use. To develop motivation, a treatment program is described in terms of motivational progression: (1) confrontation of the problem; (2) development of an intellectual understanding of the problem and its harmful effects; and (3) development of…

First-line treatment of advanced ALK-positive non-small-cell lung cancer

PubMed Central

Gandhi, Shipra; Chen, Hongbin; Zhao, Yujie; Dy, Grace K

2015-01-01

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4) gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC. PMID:28210152

Treatment in England of Canadian Patients Addicted to Narcotic Drugs

PubMed Central

Frankau, Lady

1964-01-01

The method of treatment and the results obtained from the treatment of 50 Canadian patients addicted to narcotic drugs who went to England are recorded. These patients were first stabilized on the minimal dose of narcotic drug which permitted them to work, and to acquire security and self-respect. Then, after psychiatric treatment dealing with the basic problem of their personality disorder, complete withdrawal treatment of the narcotic drug was undertaken. Nine of 10 patients aged between 20 and 30, of good social and cultural background, have been relieved of dependence on drugs for over two years. The other 40 patients came from a different background. Nearly all had been imprisoned for drug offences and they had come to England to obtain treatment and to avoid further prison sentences in Canada. The 31 patients whose prison sentences had been directly connected with drug offences are working steadily and leading an apparently normal life. The remaining nine patients had been convicted of criminal acts before becoming addicted to narcotic drugs and, with two exceptions, the results of their treatment compare unfavourably with the other patients, seven having been convicted and imprisoned in London. PMID:14123667

Removal of the anti-cancer drug methotrexate from water by advanced oxidation processes: Aerobic biodegradation and toxicity studies after treatment.

PubMed

Lutterbeck, Carlos Alexandre; Baginska, Ewelina; Machado, Ênio Leandro; Kümmerer, Klaus

2015-12-01

Anti-cancer drugs are discussed as high risk substances in regard to human health and considered as problematic for the environment. They are of potential environmental relevance due to their poor biodegradability and toxicological properties. Methotrexate (MTX) is an antimetabolite that was introduced in the pharmaceutical market in the 40's and still today is one of the most consumed cytotoxic compounds around the world. In the present study MTX was only partially biodegraded in the closed bottle test (CBT). Therefore, it was submitted to three different advanced oxidation processes (AOPs): UV/H2O2, UV/Fe(2+)/H2O2 and UV/TiO2. The irradiation was carried out with a Hg medium-pressure lamp during 256min whereas the analytical monitoring was done through LC-UV-MS/MS and DOC analysis. MTX was easily removed in all the irradiation experiments, while the highest mineralization values and rates were achieved by the UV/Fe(2+)/H2O2 treatment. The lowest resulted from the UV/H2O2 reactions. The UV/H2O2 treatment resulted in little biodegradable transformation products (TPs). However, the same treatment resulted in a reduction of the toxicity of MTX by forming less toxic TPs. Analysis by LC-UV-MS/MS revealed the existence of nine TPs formed during the photo-catalytic treatments. The pH of the solutions decreased from 6.4 (t 0min) to 5.15 in the UV/H2O2 and from 6.4 (t 0min) to 5.9 in the UV/TiO2 at the end of the experiments. The initial pH of the UV/Fe(2+)/H2O2 experiments was adjusted to 5 and after the addition of H2O2 the pH decreased to around 3 and remained in this range until the end of the treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Principles of Drug Addiction Treatment: A Research-Based Guide.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

This booklet can function as a resource for counselors, counselors in training, or anyone else who works with or knows someone who is addicted to drugs. It begins by identifying 13 principles of effective treatment for drug abusers. It then provides answers to 11 frequently asked questions regarding drug addiction treatment. Next it discusses drug…

Human toxocariasis: current advances in diagnostics, treatment, and interventions.

PubMed

Moreira, Gustavo Marçal Schmidt Garcia; Telmo, Paula de Lima; Mendonça, Marcelo; Moreira, Angela Nunes; McBride, Alan John Alexander; Scaini, Carlos James; Conceição, Fabricio Rochedo

2014-09-01

Toxocariasis is a neglected zoonosis caused by the nematodes Toxocara canis and Toxocara cati. This disease is widespread in many countries, reaching high prevalence independently of the economic conditions. However, the true number of cases of toxocariasis is likely to be underestimated owing to the lack of adequate surveillance programs. Although some diagnostic tests are available, their sensitivity and specificity need to be improved. In addition, treatment options for toxocariasis are limited and are non-specific. Toxocariasis is listed as one of the five most important neglected diseases by the CDC. This review presents recent advances related to the control of toxocariasis, including new immunodiagnostics, therapies, and drug formulations, as well as novel interventions using DNA vaccines, immunomodulators, and probiotics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

PubMed

Sørensen, Janina Maria

2002-06-01

Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided.

Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

PubMed Central

Zajdel, Justyna

2013-01-01

Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update.

PubMed

Kaneko, Shuichi; Furuse, Junji; Kudo, Masatoshi; Ikeda, Kenji; Honda, Masao; Nakamoto, Yasunari; Onchi, Morikazu; Shiota, Goshi; Yokosuka, Osamu; Sakaida, Isao; Takehara, Tetsuo; Ueno, Yoshiyuki; Hiroishi, Kazumasa; Nishiguchi, Shuhei; Moriwaki, Hisataka; Yamamoto, Kazuhide; Sata, Michio; Obi, Shuntaro; Miyayama, Shiro; Imai, Yukinori

2012-06-01

The "Guideline on the Use of New Anticancer Drugs for the Treatment of Hepatocellular Carcinoma" was prepared by the Study Group on New Liver Cancer Therapies established by the "Research Project on Emergency Measures to Overcome Hepatitis" under the auspices of the Health and Labour Sciences Research Grant. The Guideline brings together data collected by the Study Group on the use and incidence of adverse events in 264 patients with advanced hepatocellular carcinoma (HCC) treated using sorafenib and in 535 patients with advanced HCC treated using miriplatin at 16 participating institutions up until 22 December 2010, as well as referring to the published studies, academic presentations, and reports from the private sector. The aim of this Guideline is to facilitate understanding and current thinking regarding the proper usage of new anticancer drugs towards actual use in therapy. In terms of the format, the Guideline presents "clinical questions" on issues pertaining to medical care, makes "recommendations" on diagnosis and treatment in response to each of these clinical questions, and provides a rationale for these recommendations in the form of "scientific statements". © 2012 The Japan Society of Hepatology.

Clinically relevant characteristics associated with early treatment drug use versus abstinence.

PubMed

Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

2014-04-04

This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

Advancement in integrin facilitated drug delivery.

PubMed

Arosio, Daniela; Casagrande, Cesare

2016-02-01

The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

PubMed Central

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Background Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. Patients and methods This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Results Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63–7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Conclusion Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects. PMID:29075129

Associations with substance abuse treatment completion in drug court

PubMed Central

Brown, Randall T

2009-01-01

Subjects in the study included all participants (N = 573) in drug treatment court in a mid-sized U.S. city from 1996 through 2004. Administrative data from the drug court included measures of demographics and socioeconomics, substance use, and criminal justice history. Stepwise multivariate logistic regression yielded a final model of failure to complete drug treatment. Unemployment, lower educational attainment, and cocaine use disorders were associated with failure to complete treatment. The limitations of administrative data should be considered in the interpretation of results. Funding was provided by the National Institutes of Health, National Institute on Drug Abuse (1 K23 DA017283-01). PMID:20380560

Psychotropic drugs in opioid addicts on methadone treatment.

PubMed

Ferris, G N

1976-07-01

Psychotropic drug treatment of persons on methadone maintenance is discussed. Patients with clear target symptoms, such as anxiety, depression, or psychosis responded just as non-opioid addicts would to the major psychotropic agents. The minor tranquilizers are felt to be of doubtful value, and subject to abuse. Sleep disturbances cannot be treated by the usual means, as the drugs needed again are abused. However, chlorpromazine shows some promise here. Methods of drug delivery and goals of treatment must be adapted to the realities of this patient-group's characteristics, particularly anti-social traits, poor motivation and unreliability. Psychotropic drugs are unlikely to be of aid in multiple drug abusers, personality and character disorders, and opioid withdrawal. Four case histories are presented.

Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

PubMed

Holodniy, Mark; Brown, Sheldon T; Cameron, D William; Kyriakides, Tassos C; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-03-31

Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Clinicaltrials.gov NCT00050089.

Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer.

PubMed

Senkowski, Wojciech; Zhang, Xiaonan; Olofsson, Maria Hägg; Isacson, Ruben; Höglund, Urban; Gustafsson, Mats; Nygren, Peter; Linder, Stig; Larsson, Rolf; Fryknäs, Mårten

2015-06-01

Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. ©2015 American Association for Cancer Research.

The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

PubMed

Pringle, Abbie; Harmer, Catherine J

2015-12-01

Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

Advanced cell culture techniques for cancer drug discovery.

PubMed

Lovitt, Carrie J; Shelper, Todd B; Avery, Vicky M

2014-05-30

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

Advanced Cell Culture Techniques for Cancer Drug Discovery

PubMed Central

Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

2014-01-01

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

Crizotinib treatment for advanced non-small-cell lung cancer patients: a budget impact analysis based in Thailand.

PubMed

Thongprasert, Sumitra; Permsuwan, Unchalee

2017-05-01

With the advent of the anaplastic lymphoma kinase (ALK) inhibitor, treatment of ALK-positive advanced non-small-cell lung cancer (NSCLC) patients has become more effective while drug costs are still a major concern. This study aimed to estimate the budget impact of crizotinib versus other standard therapies in Thai advanced NSCLC patients with ALK rearrangement. The budget impact model was developed to estimate the net budget impact of crizotinib compared with no crizotinib considering the payer's perspective over a three-year period. Costs included drugs, ALK testing by FISH, adverse event treatment, administration and monitoring, and best supportive care. Data on costs and population were from a database in Thailand. Costs were presented for the year 2015. A univariate sensitivity analysis was performed to investigate the robustness of our findings. The total net budget impact of crizotinib in three years was 125,576,699 THB (3,480,507 USD), 91,156,049 THB (2,526,498 USD), and 42,724,760 THB (1,184,167 USD) respectively. When considering only patients receiving crizotinib, the expenditure increased by 41,199.70 THB (1141.90 USD), 20,755.02 THB (575.25 USD), and 8834.73 THB (244.87 USD) per patient per month. The main driven costs were from the cost of ALK testing and drugs. Despite its treatment value in ALK-positive patients, crizotinib can only be affordable for Thai patients within upper middle or high economic status. Availability for all patients under current payment models is limited.

Pregnancy and race/ethnicity as predictors of motivation for drug treatment.

PubMed

Mitchell, Mary M; Severtson, S Geoff; Latimer, William W

2008-01-01

While drug use during pregnancy represents substantial obstetrical risks to mother and baby, little research has examined motivation for drug treatment among pregnant women. We analyzed data collected between 2000 and 2007 from 149 drug-using women located in Baltimore, Maryland. We hypothesized that pregnant drug-using women would be more likely than non-pregnant drug-using women to express greater motivation for treatment. Also, we explored race/ethnicity differences in motivation for treatment. Propensity score analysis was used to match a sample of 49 pregnant drug-using women with 100 non-pregnant drug-using women. The first logistic regression model indicated that pregnant women were more than four times as likely as non-pregnant women to express greater motivation for treatment. The second logistic regression analysis indicated a significant interaction between pregnancy status and race/ethnicity, such that white pregnant women were nearly eight times as likely as African-American pregnant women to score higher on the motivation for treatment measure. These results suggest that African-American pregnant drug-using women should be targeted for interventions that increase their motivation for treatment.

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

PubMed Central

Chang, Xiubao; Zhu, Yuanxiao; Shi, Changxin; Stewart, A. Keith

2014-01-01

Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields. PMID:24374776

Alcohol and drug abusers' reasons for seeking treatment.

PubMed

Cunningham, J A; Sobell, L C; Sobell, M B; Gaskin, J

1994-01-01

Clients at two different treatment facilities were asked at assessment how influential each of 10 possible reasons were in their decision to change their alcohol or drug use. Clients at both facilities most often endorsed "weighing the pros and cons of drinking or drug use" and a "warning from spouse." Client's reasons for seeking treatment were also examined in relation to treatment compliance. Three reasons--"weighing the pros and cons," "hitting rock bottom," and experiencing a "major lifestyle change"--were predictive of treatment compliance. Clients who rated any of these reasons as influential were more likely to enter and complete treatment. Although more research is needed, knowledge of clients' reasons for seeking treatment might be useful in treatment matching.

Personalizing Drug Selection Using Advanced Clinical Decision Support

PubMed Central

Pestian, John; Spencer, Malik; Matykiewicz, Pawel; Zhang, Kejian; Vinks, Alexander A.; Glauser, Tracy

2009-01-01

This article describes the process of developing an advanced pharmacogenetics clinical decision support at one of the United States’ leading pediatric academic medical centers. This system, called CHRISTINE, combines clinical and genetic data to identify the optimal drug therapy when treating patients with epilepsy or Attention Deficit Hyperactivity Disorder. In the discussion a description of clinical decision support systems is provided, along with an overview of neurocognitive computing and how it is applied in this setting. PMID:19898682

The motivation for drug abuse treatment: testing cognitive and 12-step theories.

PubMed

Bell, D C; Montoya, I D; Richard, A J; Dayton, C A

1998-11-01

The purpose of this paper is to evaluate two models of behavior change: cognitive theory and 12-step theory. Research subjects were drawn from three separate, but parallel, samples of adults. The first sample consisted of out-of-treatment chronic drug users, the second consisted of drug users who had applied for treatment at a publicly funded multiple-provider drug treatment facility, and the third consisted of drug users who had applied for treatment at an intensive outpatient program for crack cocaine users. Cognitive theory was supported. Study participants applying for drug abuse treatment reported a higher level of perceived problem severity and a higher level of cognitive functioning than out-of-treatment drug users. Two hypotheses drawn from 12-step theory were not supported. Treatment applicants had more positive emotional functioning than out-of-treatment drug users, and one treatment-seeking sample had higher self-esteem.

New drugs and regimens for treatment of TB

PubMed Central

Leibert, Eric; Rom, William N

2013-01-01

Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

Illicit Drug Use and Treatment in South Africa

PubMed Central

Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D.; Phaswana-Mafuya, Nancy

2008-01-01

This review synthesizes available epidemiological data on current drug use and substance abuse treatment admissions in south africa since 1994, and how changes in the political, economic and social structures within south africa both before and after apartheid make the country more vulnerable to drug use. based on national surveys current use of cannabis ranged among adolescents from 2% to 9% and among adults 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%) and hallucinogens (0.1%). The primary illicit substance at admission to South African drug treatment centers was cannabis 16.9%, methamphetamine (Tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC 2.6%. An increase in substance abuse treatment admissions has occurred. While the prevalence of illicit drug use in South Africa is relatively low compared to the USA and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review. PMID:21039113

Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

PubMed

Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

2016-01-01

Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Prediction of antiepileptic drug treatment outcomes using machine learning.

PubMed

Colic, Sinisa; Wither, Robert G; Lang, Min; Zhang, Liang; Eubanks, James H; Bardakjian, Berj L

2017-02-01

Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Previous work have linked the presence of cross-frequency coupling (I CFC ) of the delta (2-5 Hz) rhythm with the fast ripple (400-600 Hz) rhythm in epileptiform discharges. Using the I CFC to label post-treatment outcomes we compared support vector machines (SVMs) and random forest (RF) machine learning classifiers for providing likelihood scores of successful treatment outcomes. (a) There was heterogeneity in AED treatment outcomes, (b) machine learning techniques could be used to rank the efficacy of AEDs by estimating likelihood scores for successful treatment outcome, (c) I CFC features yielded the most effective a priori identification of appropriate AED treatment, and (d) both classifiers performed comparably. Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life.

Immunotherapy for the treatment of drug abuse.

PubMed

Kosten, Thomas; Owens, S Michael

2005-10-01

Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic antagonism, which reduces the amount of drug in the brain, the rate of clearance across the blood-brain barrier, and the volume of drug distribution. Because the antibodies remain primarily in the circulatory system, they have no apparent central nervous system side effects. Active immunization with drug-protein conjugate vaccines has been tested for cocaine, heroin, methamphetamine, and nicotine in animal, with 1 cocaine and 3 nicotine vaccines in Phase 2 human trials. Passive immunization with high affinity monoclonal antibodies has been tested for cocaine, methamphetamine, nicotine, and phencyclidine (PCP) in preclinical animal models. Antibodies have 2 immediate clinical applications in drug abuse treatment: to treat drug overdose and to reduce relapse to drug use in addicted patients. The specificity of the therapies, the lack of addiction liability, minimal side effects, and long-lasting protection against drug use offer major therapeutic benefit over conventional small molecule agonists and antagonists. Immunotherapies can also be combined with other antiaddiction medications and enhance behavioral therapies. Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.

Fixed-dose combination drugs for tuberculosis: application in standardised treatment regimens.

PubMed

Blomberg, Bjørn; Fourie, Bernard

2003-01-01

Short-course chemotherapy is highly efficacious in treating tuberculosis (TB). However, the length (>/=6 months) and complexity (three or four different drugs) of the treatment makes adherence difficult. Erratic treatment not only fails to cure patients but also creates chronically contagious cases, who may excrete drug-resistant TB bacteria. The Directly Observed Treatment Short-course (DOTS) strategy recommended by WHO provides a comprehensive organisational and infrastructural framework for the rational use of diagnosis, drug supply, as well as case and programme management services, in TB control. WHO and other organisations recommend fixed-dose combination formulations (FDCs) as a further step to facilitate the optimal drug treatment of TB. Using FDCs in TB control will simplify the doctor's prescription and patient's drug intake, as well as the drug supply management of the programme. By preventing monotherapy and facilitating the ingestion of adequate doses of the constituent anti-TB drugs, FDCs are expected to help prevent the emergence of drug resistance. This article presents the international recommendations for the use of FDCs in TB programmes. The fundamental issue is to obtain drug supplies of good quality. A laboratory network for quality testing, including bioavailability testing of FDCs exists, and the recently established Global TB Drug Facility (GDF) supplies quality TB drugs, including 4-drug FDCs, to countries requesting assistance. This articles deals with the requirements for a successful transition to FDC-based treatment. It emphasises the need for appropriately revised programme documentation (programme manual, training modules, treatment guidelines and forms), training of staff at all levels, carefully calculated drug needs, and a plan for the exhaustion of existing stocks of loose tablets and the phasing-in of FDCs at all levels of the programme at the same time. Loose drugs for individualised treatment of patients with adverse effects

The economics of public health: financing drug abuse treatment services.

PubMed

Cartwright, William S; Solano, Paul L

2003-12-01

Drug abuse treatment financing exhibits a heterogeneous set of sources from federal, state, and local governments, as well as private sources from insurance, patient out-of-pocket, and charity. A public health model of drug abuse treatment is presented for a market that can be characterized by excess demand in many communities and an implied policy of rationing. According to best estimates, as many as 6.7 million individuals may need treatment, but only an estimated 1.5 million individuals actually participated in treatment episodes. Since, as demonstrated empirically, drug abuse treatment has a robust and positive social net benefit to society, it is perplexing that treatment financing stops with a rationing outcome that inhibits social welfare. The justification for public financing is centered on the external costs of drug addiction, but subsidization is grounded in the reality that a large number of addicted individuals do not have sufficient resources to pay for treatment out-of-pocket, nor do they have private insurance coverage. Social welfare losses are generated by financial arrangements that are inconsistent with rational budgeting theory and as such would lead to non-optimal organization and management of the drug abuse treatment system.

Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis

PubMed Central

Kraus, Virginia Byers; Burnett, Bruce; Coindreau, Javier; Cottrell, Susan; Eyre, David; Gendreau, Michael; Gardiner, Jennifer; Garnero, Patrick; Hardin, John; Henrotin, Yves; Heinegård, Dick; Ko, Amy; Lohmander, Stefan; Matthews, Gloria; Menetski, Joseph; Moskowitz, Roland; Persiani, Stefano; Poole, Robin; Rousseau, Jean Charles; Todman, Martin

2013-01-01

increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. PMID:21396468

The drug-drug interaction potential of antiviral agents for the treatment of chronic hepatitis C infection.

PubMed

Garrison, Kimberly L; German, Polina; Mogalian, Erik; Mathias, Anita

2018-04-25

Several safe and highly-effective directly-acting antiviral drugs for chronic hepatitis C virus (HCV) have been developed and greatly increase the number of treatment options available to successfully treat HCV infection. However, as treatment regimens contain at least two drugs (e.g., sofosbuvir with daclatasvir, simeprevir, ledipasvir, or velpatasvir; elbasvir and grazoprevir) and up to five drugs (ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin), the potential for drug-drug interactions (DDI) becomes an important consideration for HCV-infected individuals with comorbidities that require concomitant medications, such as HIV/HCV co-infection or immunosuppression following liver transplantation. This review details the pharmacokinetics and DDI potential of approved DAAs for the treatment of HCV infection. The American Society for Pharmacology and Experimental Therapeutics.

Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

PubMed Central

Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-01-01

Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

Problems of long-term spinal opioid treatment in advanced cancer patients.

PubMed

Mercadante, S

1999-01-01

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different

Emerging drugs for the treatment of erectile dysfunction.

PubMed

Peak, Taylor C; Yafi, Faysal A; Sangkum, Premsant; Hellstrom, Wayne J G

2015-06-01

Erectile dysfunction adversely affects the lives of millions of men, and is the most commonly treated sexual disorder today. The erectile process has been extensively investigated, with major advances made in elucidating many of the complex molecular pathways involved. These advances have allowed researchers to design and study drug formulations that target various aspects of this complex process. The initial culmination of this research was the introduction of phosphodiesterase 5-inhibitors. While effective in many patients, they are not satisfactory for all afflicted men. As a result, researchers are developing novel drugs that target different molecular pathways. The paper will review these pathways, and the potential agents that target them. More specifically, first dopaminergic and melanocortin receptor agonists that act centrally will be covered. Then, the paper will examine the "second-generation" phosphodiesterase 5-inhibitors, soluble guanylate cyclases, rho-kinase inhibitors, and maxi-k channel activators that act peripherally. Most of these novel drugs have yet to reach Phase III studies. However, it is likely that in years to come, patients will be selectively treated with these novel agents as a monotherapy or in combination with others acting in a synergistic manner.

Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

PubMed

Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

2017-03-01

Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

Current Advances in Polymer-Based Nanotheranostics for Cancer Treatment and Diagnosis

PubMed Central

2015-01-01

Nanotheranostics is a relatively new, fast-growing field that combines the advantages of treatment and diagnosis via a single nanoscale carrier. The ability to bundle both therapeutic and diagnostic capabilities into one package offers exciting prospects for the development of novel nanomedicine. Nanotheranostics can deliver treatment while simultaneously monitoring therapy response in real-time, thereby decreasing the potential of over- or under-dosing patients. Polymer-based nanomaterials, in particular, have been used extensively as carriers for both therapeutic and bioimaging agents and thus hold great promise for the construction of multifunctional theranostic formulations. Herein, we review recent advances in polymer-based systems for nanotheranostics, with a particular focus on their applications in cancer research. We summarize the use of polymer nanomaterials for drug delivery, gene delivery, and photodynamic therapy, combined with imaging agents for magnetic resonance imaging, radionuclide imaging, and fluorescence imaging. PMID:25014486

[Accreditation standards concerning patients' rights: a review of the current state of affairs related to drug-addiction treatment centers in Colombia].

PubMed

Zapata-Vanegas, Mario A

2014-01-01

Characterizing and contrasting the current state of affairs concerning patients' rights-associated accreditation standards in a sample of drug-addiction treatment centers in Colombia. This was mixed methodology research (i.e. descriptive and hermeneutic); a pilot sample of 21 drug-addiction treatment centers in Colombia was used for determining the current state of patients' rights accreditation standards. The possible relationship or independence between categorical variables was evaluated by using Fisher's exact test (0.05 significance level). A contrasting documentary review was made at the same time. Drug-addiction treatment centers provided more information for families (95 %) than patients (90 %) or minors (81 %). Possible barriers to gaining access for treatment were being HIV positive (29 %), being part of the LGTB population (14 %) and being female (10 %); religion and ethnicity were not seen as grounds for discrimination or treatment barriers. The patients' rights standards group coincided with Colombia's accreditation system and Joint Commission standards; however, the latter accreditation entity has made significant progress regarding a specific manual for drug-addiction treatment centers. The centers assessed in Colombia had made advances regarding accrediting patients' rights, but such standards require revision for being adapted to international developments and specific matters involved in treating addicts and the specific conditions for institutions dealing with such treatment.

Pregnancy and Race/Ethnicity as Predictors of Motivation for Drug Treatment

PubMed Central

Mitchell, Mary M.; Severtson, S. Geoff; Latimer, William W.

2009-01-01

While drug use during pregnancy represents substantial obstetrical risks to mother and baby, little research has examined motivation for drug treatment among pregnant women. We analyzed data collected between 2000 and 2007 from 149 drug-using women located in Baltimore, Maryland. We hypothesized that pregnant drug-using women would be more likely than their non-pregnant counterparts to express greater motivation for treatment. Also, we explored race/ethnicity differences in motivation for treatment. Propensity scores were used to match a sample of 49 pregnant drug-using women with 100 non-pregnant drug-using women. A factor analysis using 11 items from a readiness for treatment scale was used to create a dichotomous outcome variable representing higher and lower levels of motivation for treatment. The first logistic regression model indicated that pregnant women were more than four times as likely as non-pregnant women to express greater motivation for treatment. The second logistic regression analysis indicated a significant interaction between pregnancy status and race/ethnicity, such that white pregnant women were nearly eight times as likely as African-American pregnant women to score higher on the motivation for treatment measure. These results suggest that African-American pregnant drug-using women should be targeted for interventions that increase their motivation for treatment. PMID:18584569

28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...

28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...

28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...

28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...

28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

Drug rechallenge and treatment beyond progression—implications for drug resistance

PubMed Central

Kuczynski, Elizabeth A.; Sargent, Daniel J.; Grothey, Axel; Kerbel, Robert S.

2015-01-01

The established dogma in oncology for managing recurrent or refractory disease dictates that therapy is changed at disease progression, because the cancer is assumed to have become drug-resistant. Drug resistance, whether pre-existing or acquired, is largely thought to be a stable and heritable process; thus, reuse of therapeutic agents that have failed is generally contraindicated. Over the past few decades, clinical evidence has suggested a role for unstable, non-heritable mechanisms of acquired drug resistance pertaining to chemotherapy and targeted agents. There are many examples of circumstances where patients respond to reintroduction of the same therapy (drug rechallenge) after a drug holiday following disease relapse or progression during therapy. Additional, albeit limited, evidence suggests that, in certain circumstances, continuing a therapy beyond disease progression can also have antitumour activity. In this Review, we describe the anticancer agents used in these treatment strategies and discuss the potential mechanisms explaining the apparent tumour re-sensitization with reintroduced or continued therapy. The extensive number of malignancies and drugs that challenge the custom of permanently switching to different drugs at each line of therapy warrants a more in-depth examination of the definitions of disease progression and drug resistance and the resulting implications for patient care. PMID:23999218

Dynamic effects among patients' treatment needs, beliefs, and utilization: a prospective study of adolescents in drug treatment.

PubMed

Schell, Terry L; Orlando, Maria; Morral, Andrew R

2005-08-01

To document the prospective, reciprocal relationships among substance use problems, utilization of drug treatment, and predisposing beliefs thought to increase treatment utilization. Persistent Effects of Treatment Study-Adolescent (PETS-A), conducted by the Center on Substance Abuse Treatment. This was a longitudinal study of youths originally participating in one of two CSAT studies; one sample included 476 youths receiving residential drug treatment, and the other included 519 youths receiving outpatient treatment. This study uses five waves of data collected over a 12-month period to examine the temporal relationships among four variables: treatment dose, substance use problems, drug resistance self-efficacy, and perceived need for treatment (PNT). Data from this longitudinal study were analyzed using cross-lagged panel models, and structural equation modeling techniques were used to estimate the prospective, reciprocal relationships among these four variables in each of the two samples, while controlling for several covariates. Both PNT and low drug resistance self-efficacy led to higher levels of subsequent treatment. However, low self-efficacy presaged increases in drug problems while PNT predicted decreases. Understanding the role of psychological variables in the utilization of health services is complicated for psychological disorders because beliefs that affect treatment can also influence the disorder itself. Efforts to keep adolescents in drug treatment should focus on convincing youth that treatment can help them with their problems, rather than convincing them that they cannot resist drugs on their own. While both messages increase treatment utilization, the latter belief undermines the effects of treatment.

Dynamic Effects among Patients' Treatment Needs, Beliefs, and Utilization: A Prospective Study of Adolescents in Drug Treatment

PubMed Central

Schell, Terry L; Orlando, Maria; Morral, Andrew R

2005-01-01

Objective To document the prospective, reciprocal relationships among substance use problems, utilization of drug treatment, and predisposing beliefs thought to increase treatment utilization. Data Source Persistent Effects of Treatment Study-Adolescent (PETS-A), conducted by the Center on Substance Abuse Treatment. This was a longitudinal study of youths originally participating in one of two CSAT studies; one sample included 476 youths receiving residential drug treatment, and the other included 519 youths receiving outpatient treatment. Study Design This study uses five waves of data collected over a 12-month period to examine the temporal relationships among four variables: treatment dose, substance use problems, drug resistance self-efficacy, and perceived need for treatment (PNT). Data from this longitudinal study were analyzed using cross-lagged panel models, and structural equation modeling techniques were used to estimate the prospective, reciprocal relationships among these four variables in each of the two samples, while controlling for several covariates. Principal Findings Both PNT and low drug resistance self-efficacy led to higher levels of subsequent treatment. However, low self-efficacy presaged increases in drug problems while PNT predicted decreases. Conclusions Understanding the role of psychological variables in the utilization of health services is complicated for psychological disorders because beliefs that affect treatment can also influence the disorder itself. Efforts to keep adolescents in drug treatment should focus on convincing youth that treatment can help them with their problems, rather than convincing them that they cannot resist drugs on their own. While both messages increase treatment utilization, the latter belief undermines the effects of treatment. PMID:16033496

Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

PubMed

Tutton, P J; Barkla, D H

1978-08-25

A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.

Drug delivery strategies for Alzheimer's disease treatment.

PubMed

Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

2011-05-01

Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Prediction of antiepileptic drug treatment outcomes using machine learning

NASA Astrophysics Data System (ADS)

Colic, Sinisa; Wither, Robert G.; Lang, Min; Zhang, Liang; Eubanks, James H.; Bardakjian, Berj L.

2017-02-01

Objective. Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. Approach. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Previous work have linked the presence of cross-frequency coupling (I CFC) of the delta (2-5 Hz) rhythm with the fast ripple (400-600 Hz) rhythm in epileptiform discharges. Using the I CFC to label post-treatment outcomes we compared support vector machines (SVMs) and random forest (RF) machine learning classifiers for providing likelihood scores of successful treatment outcomes. Main results. (a) There was heterogeneity in AED treatment outcomes, (b) machine learning techniques could be used to rank the efficacy of AEDs by estimating likelihood scores for successful treatment outcome, (c) I CFC features yielded the most effective a priori identification of appropriate AED treatment, and (d) both classifiers performed comparably. Significance. Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life.

Microchips and controlled-release drug reservoirs.

PubMed

Staples, Mark

2010-01-01

This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations.

PubMed

Imai, Hisao; Minemura, Hiroyuki; Sugiyama, Tomohide; Yamada, Yutaka; Kaira, Kyoichi; Kanazawa, Kenya; Kasai, Takashi; Kaburagi, Takayuki; Minato, Koichi

2018-05-08

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded. Overall, 20 patients with a median age of 79.5 years (range 75-85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted. Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first

Malaria treatment using novel nano-based drug delivery systems.

PubMed

Baruah, Uday Krishna; Gowthamarajan, Kuppusamy; Vanka, Ravisankar; Karri, Veera Venkata Satyanarayana Reddy; Selvaraj, Kousalya; Jojo, Gifty M

2017-08-01

We reside in an era of technological innovation and advancement despite which infectious diseases like malaria remain to be one of the greatest threats to the humans. Mortality rate caused by malaria disease is a huge concern in the twenty-first century. Multiple drug resistance and nonspecific drug targeting of the most widely used drugs are the main reasons/drawbacks behind the failure in malarial therapy. Dose-related toxicity because of high doses is also a major concern. Therefore, to overcome these problems nano-based drug delivery systems are being developed to facilitate site-specific or target-based drug delivery and hence minimizing the development of resistance progress and dose-dependent toxicity issues. In this review, we discuss about the shortcomings in treating malaria and how nano-based drug delivery systems can help in curtailing the infectious disease malaria.

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among methadone maintenance treatment patients.

PubMed

Potik, David; Peles, Einat; Abramsohn, Yahli; Adelson, Miriam; Schreiber, Shaul

2014-01-01

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among patients in methadone maintenance treatment (MMT) was examined by the Vulnerable Attachment Style Questionnaire (VASQ), the Symptom Checklist-90 (SCL-90), and drug abuse urine tests. After six years, retention in treatment and repeated urine test results were studied. Patients with vulnerable attachment style (a high VASQ score) had higher rates of drug abuse and higher psychopathology levels compared to patients with secure attachment style, especially on the interpersonal sensitivity, anxiety, hostility, phobic anxiety, and paranoid ideation scales. Drug abstinence at baseline was related to retention in treatment and to higher rates of drug abstinence after six years in MMT, whereas a vulnerable attachment style could not predict drug abstinence and retention in treatment. Clinical Implications concerning treatment of drug abusing populations and methodological issues concerning the VASQ's subscales are also discussed.

[Treatment approaches for synthetic drug addiction].

PubMed

Kobayashi, Ohji

2015-09-01

In Japan, synthetic drugs have emerged since late 2000s, and cases of emergency visits and fatal traffic accidents due to acute intoxication have rapidly increased. The synthetic drugs gained popularity mainly because they were cheap and thought to be "legal". The Japanese government restricted not only production and distribution, but also its possession and use in April 2014. As the synthetic drug dependent patients have better social profiles compared to methamphetamine abusers, this legal sanction may have triggered the decrease in the number of synthetic drug dependent patient visits observed at Kanagawa Psychiatric Center since July 2014. Treatment of the synthetic drug dependent patients should begin with empathic inquiry into the motives and positive psychological effects of the drug use. In the maintenance phase, training patients to trust others and express their hidden negative emotions through verbal communications is essential. The recovery is a process of understanding the relationship between psychological isolation and drug abuse, and gaining trust in others to cope with negative emotions that the patients inevitably would face in their subsequent lives.

Implicit and Explicit Drug-Related Cognitions during Detoxification Treatment Are Associated with Drug Relapse: An Ecological Momentary Assessment Study

ERIC Educational Resources Information Center

Marhe, Reshmi; Waters, Andrew J.; van de Wetering, Ben J. M.; Franken, Ingmar H. A.

2013-01-01

Objective: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with…

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

PubMed Central

Choi, Rihwa; Jeong, Byeong-Ho

2017-01-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

PubMed

Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

2017-03-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

Drug Court Effectiveness: A Matched Cohort Study in the Dane County Drug Treatment Court

ERIC Educational Resources Information Center

Brown, Randall

2011-01-01

Drug treatment courts (DTCs) are widely viewed as effective diversion programs for drug-involved offenders; however, previous studies frequently used flawed comparison groups. In the current study, the author compared rates of recidivism for drug court participants to rates for a traditionally adjudicated comparison group matched on potentially…

Recovery among Adolescents: Models for Post-Treatment Gains in Drug Abuse Treatments

PubMed Central

Joe, George W.; Knight, Danica Kalling; Becan, Jennifer E.; Flynn, Patrick M.

2013-01-01

Recovery among adolescents undergoing substance abuse treatment was modeled in terms of pre-treatment motivation, therapeutic relationships, psychological functioning, treatment retention, legal pressures, DSM diagnoses, and client demographics. To address between program differences, a within-covariance matrix, based on 547 youth, was used. Applicability of the results across treatment modalities was also examined. The data were from the NIDA-sponsored DATOS Adolescent study. Results from structural equation models (estimated using Mplus) indicated that higher pre-treatment motivation predicted stronger counselor and in-treatment peer relationships, better counselor relationships and retention predicted less illegal drug use at follow-up, and DSM diagnosis was important in the treatment process. Overall, illegal drug use at follow-up was associated with post-treatment alcohol consumption, cigarette use, condom nonuse, psychological distress, criminality, and school non-attendance. The results document the importance of motivation and therapeutic relationships on recovery, even when taking into account the relative effects of legal pressures, DSM diagnoses, and demographics. PMID:24238715

[The Nature and Issues of Drug Addiction Treatment under Constraint].

PubMed

Quirion, Bastien

This article is exploring different forms of constraint that are exerted in the field of drug addiction treatment. The objective of this article is to establish benchmarks and to stimulate reflection about the ethical and clinical implications of those constraints in the field of drug addiction treatment. This article is presenting a critical review of different forms of constraint that can be exerted in Canada in regard to the treatment of drug addiction. In the first section of the article, a definition of therapeutic intervention is proposed, that includes the dimension of power, which justifies the importance of considering the coercive aspects of treatment. The second section, which represents the core section of the paper, is devoted to the presentation of different levels of constraint that can be distinguished in regard to drug addicts who are under treatment. Three levels of constraint are exposed: judicial constraint, institutional constraint and relational constraint. The coercive aspect of treatment can then be recognized as a combination of all tree levels of constraint. Judicial constraint refers to any form of constraint in which the court or the judge is imposing or recommending treatment. This particular level of constraint can take different forms, such as therapeutic remands, conditions of a probation order, conditions of a conditional sentence of imprisonment, and coercive treatment such as the ones provided through drug courts. Institutional constraint refers to any form of constraint exerted within any institutional setting, such as correctional facilities and programs offered in community. Correctional facilities being limited by their own specific mission, it might have a major impact on the way the objectives of treatment are defined. Those limitations can then be considered as a form of constraint, in which drug users don't have much space to express their personal needs. Finally, relational constraint refers to any form of constraint in

From wanting to willing - controlled drug use as a treatment goal.

PubMed

Järvinen, Margaretha

2017-03-01

This paper uses rational choice theory to analyse a new - and controversial - treatment approach to drug problems: services aimed at making clients capable of controlled use of illegal drugs. The paper highlights three mechanisms used in control-focused treatment: attempts to move drug use from the sphere of "wanting" to the sphere of "willing"; temporal framing of illegal drug use; and a therapeutic focus on clients' resources rather than their problems. Furthermore, the paper identifies some of the main challenges associated with this kind of treatment. The paper is based on 30 qualitative interviews with young people (aged 18-25) enrolled in drug treatment in Copenhagen, Denmark. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased risk of adverse drug events secondary to bevacizumab treatment in patients with advanced or metastatic breast cancer: a meta-analysis of randomized controlled trials.

PubMed

Shin, Sooyoung; Noh, Yoojin

2018-01-01

Several clinical trials have shown an increased risk of hypertension with bevacizumab when added to chemotherapy in different types of malignancy; however, the risks of other significant adverse events besides hypertension, specifically in breast cancer, have not been completely elucidated. This study was conducted with the aim, primarily, to assess the overall incidence and risk of common toxicities associated with bevacizumab in patients with advanced or metastatic breast cancer and, secondarily, to descriptively review study results concerning a potential correlation between bevacizumab-induced hypertension and its efficacy for breast cancer treatment. We carried out a meta-analysis of relevant randomized controlled trials (RCTs) identified from a database search (Cochrane Library and PubMed) and, additionally, by reviewing previous reviews and meta-analyses. Overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were assessed with the random- or fixed-effect models, depending on the level of heterogeneity across the included trials. The primary clinical outcomes were high-grade adverse events commonly reported with bevacizumab therapy. We included 6,260 patients with advanced-stage breast cancer from 12 RCTs in the meta-analysis. Five types of high-grade (Grade 3 or 4) adverse drug events were identified as being correlated with bevacizumab treatment versus alternative treatment with statistical significance: hypertension (OR 5.67, 95% CI 3.02-10.65), proteinuria (OR 10.09, 95% CI 4.79-21.27), bleeding (OR 3.45, 95% CI 2.25-5.30), cardiac toxicity (OR 2.15, 95% CI 1.29-3.59), and neutropenic fever (OR 1.51, 95% CI 1.15-2.00). The prognostic value of bevacizumab-induced hypertension for its antitumor efficacy among patients with breast cancer remains controversial, with mixed results presented in the five retrospective studies that were identified from our additional literature search. The addition of bevacizumab to anticancer therapy was

Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

PubMed

Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

2016-01-01

Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

Clinical Considerations of Focal Drug Delivery in Cancer Treatment.

PubMed

Harris, Jamie; Klonoski, Samuel C; Chiu, Bill

2017-01-01

According to the US Center for Disease Control, cancer deaths are the second most common cause of mortality in both adults and children. Definitive treatment of solid tumors involves surgical resection with or without systemic chemotherapy and radiation. The advent of local drug delivery presents a unique treatment modality that can offer substantial benefits in cancer management. Three main phases in solid tumor management exist for the treating physician: initial diagnosis with tissue biopsy, surgical resection with or without chemotherapy, and management of metastatic disease. A literature review of both basic science as well as clinical trials using local drug delivery strategies in the management of solid tumors was done on PubMed. These were then further divided into the categories of initial tissue biopsy intervention, surgical resection, and management of metastatic disease. A total of 27 articles were review that included both pre-clinical as well as clinical investigation of local drug delivery therapies in the treatment of solid tumors. Treatments such as MRI guided therapies, FDA approved local therapies for intracranial gliomas as well as local therapy for single site metastatic disease were identified. This review focuses the current state of local drug delivery in the treatment of solid tumors in both the pre-clinical as well as clinical investigation settings. Local drug delivery therapy offers an exciting new treatment modality for solid malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Recent Advances in Vaccines and Drugs Against the Ebola Virus].

PubMed

Zhu, Xiang; Yao, Chenguang; Wei, Yanhong; Kou, Zheng; Hu, Kanghong

2015-05-01

The Ebola virus belongs to the Filovirus family, which causes Ebola hemorrhagic fever (mortality, 25%-90%). An outbreak of infection by the Ebola virus is sweeping across West Africa, leading to high mortality and worldwide panic. The Ebola virus has caused a serious threat to public health, so intensive scientific studies have been carried out. Several vaccines (e.g., rVSV-ZEBOV, ChAd3-ZEBOV) have been put into clinical trials and antiviral drugs (e.g., TKM-Ebola, ZMAPP) have been administered in the emergency setting to patients infected by the Ebola virus. Here, recent advances in vaccines and drugs against the Ebola virus are reviewed.

Social and Structural Challenges to Drug Cessation Among Couples in Northern Mexico: Implications for Drug Treatment in Underserved Communities

PubMed Central

Bazzi, Angela Robertson; Syvertsen, Jennifer L.; Rolón, María Luisa; Martinez, Gustavo; Rangel, Gudelia; Vera, Alicia; Amaro, Hortensia; Ulibarri, Monica D.; Hernandez, Daniel O.; Strathdee, Steffanie A.

2015-01-01

Background Available drug treatment modalities may inadequately address social and structural contexts surrounding recovery efforts. Methods This mixed methods analysis drew on (1) surveys with female sex workers and their intimate male partners and (2) semi-structured interviews with a subsample of 41 couples (n = 82 individuals, 123 total interviews) in Northern Mexico. Descriptive and content analyses examined drug cessation and treatment experiences. Results Perceived need for drug treatment was high, yet only 35% had ever accessed services. Financial and institutional barriers (childcare needs, sex-segregated facilities) prevented partners from enrolling in residential programs together or simultaneously, leading to self-treatment attempts. Outpatient methadone was experienced more positively, yet financial constraints limited access and treatment duration. Relapse was common, particularly when one partner enrolled alone while the other continued using drugs. Conclusions Affordable, accessible, evidence-based drug treatment and recovery services that acknowledge social and structural contexts surrounding recovery are urgently needed for drug-involved couples. PMID:26470596

The emerging role of biotechnological drugs in the treatment of gout.

PubMed

Cavagna, L; Taylor, W J

2014-01-01

One of the most important therapeutic advances obtained in the field of rheumatology is the availability of the so-called bio(techno)logical drugs, which have deeply changed treatment perspectives in diseases such as rheumatoid arthritis and ankylosing spondylitis. According to the steadily increasing attention on gout, due to well-established prognostic and epidemiology implications, in the last 5 years, the same change of perspective has been observed also for this disease. In fact, several bio(techno)logical agents have been investigated both for the management of the articular gout symptoms, targeting mainly interleukin-1 β , as well as urate-lowering therapies such as recombinant uricases. Among the IL-1 β inhibitors, the majority of studies involve drugs such as anakinra, canakinumab, and rilonacept, but other compounds are under development. Moreover, other potential targets have been suggested, as, for example, the TNF alpha and IL-6, even if data obtained are less robust than those of IL-1 β inhibitors. Regarding urate-lowering therapies, the recombinant uricases pegloticase and rasburicase clearly showed their effectiveness in gout patients. Also in this case, new compounds are under development. The aim of this review is to focus on the various aspects of different bio(techno)logical drugs in gouty patients.

Recent advances in intra-articular drug delivery systems for osteoarthritis therapy.

PubMed

Maudens, Pierre; Jordan, Olivier; Allémann, Eric

2018-05-21

Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections. This paper reviews the role and interaction among different tissues involved in OA and summarizes recent clinical trials and research on DDSs, focusing on small-molecule delivery. To achieve an ideal treatment, various key criteria have been identified to design and develop an IA DDS matching the clinical needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

[The costs of new drugs compared to current standard treatment].

PubMed

Ujeyl, Mariam; Schlegel, Claudia; Gundert-Remy, Ursula

2013-01-01

Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. Copyright © 2013. Published by Elsevier GmbH.

Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma.

PubMed

Patel, Rutveej; Bock, Megan; Polotti, Charles F; Elsamra, Sammy

2017-02-01

Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression. Phase I trials confirmed antitumor activity of atezolizumab in patients with advanced or metastatic urothelial carcinoma. Phase II trials showed an improved response rate and a longer durable response than current conventional therapy. Phase III trials are currently underway with an estimated accrual end date of 2017. Expert opinion: MIBC is a high-risk disease, and after progression on current chemotherapy regimens, second-line treatments leave much to be desired. Emerging evidence of efficacy and safety and a recent accelerated approval by the FDA presents atezolizumab as a promising treatment option. Current clinical challenges include the details of disease progression and determining where immune checkpoint inhibition will reside in the treatment algorithm.

A new era of cancer treatment: carbon nanotubes as drug delivery tools

PubMed Central

Madani, Seyed Yazdan; Naderi, Naghmeh; Dissanayake, Oshani; Tan, Aaron; Seifalian, Alexander M

2011-01-01

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology. PMID:22162655

Advances in nanomedicines for malaria treatment.

PubMed

Aditya, N P; Vathsala, P G; Vieira, V; Murthy, R S R; Souto, E B

2013-12-01

Malaria is an infectious disease that mainly affects children and pregnant women from tropical countries. The mortality rate of people infected with malaria per year is enormous and became a public health concern. The main factor that has contributed to the success of malaria proliferation is the increased number of drug resistant parasites. To counteract this trend, research has been done in nanotechnology and nanomedicine, for the development of new biocompatible systems capable of incorporating drugs, lowering the resistance progress, contributing for diagnosis, control and treatment of malaria by target delivery. In this review, we discussed the main problems associated with the spread of malaria and the most recent developments in nanomedicine for anti-malarial drug delivery. © 2013.

Gout therapeutics: new drugs for an old disease.

PubMed

Burns, Christopher M; Wortmann, Robert L

2011-01-08

The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. The use of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreatable gout is progressing. Additionally, advances in our understanding of the transport of uric acid in the renal proximal tubule and the inflammatory response to monosodium urate crystals are translating into potential new treatments. In this Review, we focus on the clinical trials of febuxostat. We also review results from studies of pegloticase, a pegylated uricase in development, and we summarise data for several other pipeline drugs for gout, such as the selective uricosuric drug RDEA594 and various interleukin-1 inhibitors. Finally, we issue a word of caution about the proper use of the new drugs and the already available drugs for gout. At a time of important advances, we need to recommit ourselves to a rational approach to the treatment of gout. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rhabdomyolysis induced by antiepileptic drugs: characteristics, treatment and prognosis.

PubMed

Jiang, Wei; Wang, Xuefeng; Zhou, Shengnian

2016-01-01

Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.

Recent advances in green nanoparticulate systems for drug delivery: efficient delivery and safety concern.

PubMed

Lam, Pik-Ling; Wong, Wai-Yeung; Bian, Zhaoxiang; Chui, Chung-Hin; Gambari, Roberto

2017-02-01

Nanotechnology manipulates therapeutic agents at the nanoscale for the development of nanomedicines. However, there are current concerns over nanomedicines, mainly related to the possible toxicity of nanomaterials used for health medications. Due to their small size, they can enter the human body more readily than larger sized particles. Green chemistry encompasses the green synthesis of drug-loaded nanoparticles by reducing the use of hazardous materials in the synthesis process, thus reducing the adverse health impacts of pharmaceutics. This would greatly expand their potential in biomedical treatments. This review highlights the potential risks of nanomedicine formulations to health, delivery routes of green nanomedicines, recent advances in the development of green nanoscale systems for biomedical applications and future perspectives for the green development of nanomedicines.

Recent advances in therapeutics and drug delivery for the treatment of inner ear diseases: a patent review (2011-2015).

PubMed

Nguyen, Kim; Kempfle, Judith S; Jung, David H; McKenna, Charles E

2017-02-01

Inner ear disorders such as hearing loss, tinnitus, and Ménière's disease significantly impact the quality of life of affected individuals. Treatment of such disorders is an ongoing challenge. Current clinical approaches relieve symptoms but do not fully restore hearing, and the search for more effective therapeutic methods represents an area of urgent current interest. Areas covered: Thirty four patents and patent applications published from 2011 to 2015 were selected from the database of the U.S. Patent and Trademark Office (USPTO) and World Intellectual Property Organization (WIPO), covering new approaches for the treatment of inner ear disorders described in the patent literature: 1) identification of new therapeutic agents, 2) development of sustained release formulations, and 3) medical devices that facilitate delivery of such agents to the inner ear. Expert opinion: The search for effective treatments of inner ear disorders is ongoing. Increased understanding of the molecular mechanisms of hearing loss, Ménière's disease, and tinnitus is driving development of new therapeutic agents. However, delivery of these agents to the inner ear is a continuing challenge. At present, combination of a suitable drug with an appropriate mode of drug delivery is the key focus of innovative research to cure inner ear disorders.

Recent advances in the construction of antibody-drug conjugates

NASA Astrophysics Data System (ADS)

Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

2016-02-01

Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

The first decade of the National Drug Abuse Treatment Clinical Trials Network: bridging the gap between research and practice to improve drug abuse treatment.

PubMed

Tai, Betty; Straus, Michele M; Liu, David; Sparenborg, Steven; Jackson, Ron; McCarty, Dennis

2010-06-01

The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to improve the quality of addiction treatment using science as the vehicle. The network brings providers from community-based drug abuse treatment programs and scientists from university-based research centers together in an alliance that fosters bidirectional communication and collaboration. Collaboration enhanced the relevance of research to practice and facilitated the development and implementation of evidence-based treatments in community practice settings. The CTN's 20 completed trials tested pharmacological, behavioral, and integrated treatment interventions for adolescents and adults; more than 11,000 individuals participated in the trials. This article reviews the rationale for the CTN, describes the translation of its guiding principles into research endeavors, and anticipates the future evolution of clinical research within the Network.

Patterns of drug treatment entry by Latino male injection drug users from different national/geographical backgrounds.

PubMed

Reynoso-Vallejo, Humberto; Chassler, Deborah; Witas, Julie; Lundgren, Lena M

2008-02-01

This study examined patterns of treatment entry by Puerto Rican, Central American, Dominican, and other Latino male injection drug users (IDUs) in the state of Massachusetts over the time period 1996-2002. Specifically, it explored whether these populations had different patterns relative to three paths: entry into detoxification only, entry into residential treatment, or entry into methadone maintenance. Using a state-level MIS dataset on all substance abuse treatment entries to all licensed treatment programs, bi-variate and logistic regression methods were employed to examine patterns of drug treatment utilization among Latino men residing in Massachusetts. Three logistic regression models, which controlled for age, education, homelessness, employment, history of mental health treatment, health insurance, criminal justice involvement, having injected drugs in the past month, and number of treatment entries, indicated that Puerto Rican men were significantly less likely to only use detoxification services and residential treatment services, and significantly more likely to enter methadone maintenance compared to Latino men from Central American, Dominican, or other Latino backgrounds. For example, Central American men were 2.4 times more likely to enter only detoxification programs and 54% less likely to enter methadone maintenance programs than Puerto Rican male IDUs. For program planning, include the need to (a) develop varied drug treatment services to meet the needs of non-homogenous Latino groups within the population, (b) tailor outreach efforts to effectively reach all Latino groups, and (c) increase awareness among practitioners of differential patterns of treatment utilization.

The treatment of anxiety states by drugs and other means.

PubMed

Linford Rees, W

1979-10-27

The place of pharmacotherapy, behaviour therapy and biofeedback techniques in the general strategy of treating anxiety states is critically discussed. The dangers and disadvantages of barbiturates are described and the value and limitations of other drugs are considered. Beta-adrenergic receptor blocking drugs have a limited but valuable role in some patients, neuroleptics have a strictly limited place in treatment, and the role of antidepressants of various kinds is considered when anxiety is part of a depressive illness. The benzodiazepines are the most important group of drugs available for the treatment of anxiety states. The differences between various benzodiazepines are presented, with particular reference to their onset of action, half-life and the relevance of active metabolites of some of these drugs. A knowledge of the pharmacokinetics of the benzodiazepine drugs is of practical importance to the clinician. Emphasis is placed on the doctor-patient relationship and psychotherpeutic management in which drugs and other treatment serve as tactical aids in the general strategy of care.

Discovering drugs for the treatment of Ebola virus

DTIC Science & Technology

2017-08-04

Discovering drugs for the treatment of Ebola virus Sandra L. Bixler, Allen J. Duplantier and Sina Bavari Address United States Army Medical...with the recent West African outbreak resulting in over 11,000 deaths. This review provides a summary of the status of drug discovery and development...disease, including small molecules, immunotherapeutics, host factors, and clinical disease management options. Introduction Drug development for

Optimal Drug Synergy in Antimicrobial Treatments

PubMed Central

Torella, Joseph Peter; Chait, Remy; Kishony, Roy

2010-01-01

The rapid proliferation of antibiotic-resistant pathogens has spurred the use of drug combinations to maintain clinical efficacy and combat the evolution of resistance. Drug pairs can interact synergistically or antagonistically, yielding inhibitory effects larger or smaller than expected from the drugs' individual potencies. Clinical strategies often favor synergistic interactions because they maximize the rate at which the infection is cleared from an individual, but it is unclear how such interactions affect the evolution of multi-drug resistance. We used a mathematical model of in vivo infection dynamics to determine the optimal treatment strategy for preventing the evolution of multi-drug resistance. We found that synergy has two conflicting effects: it clears the infection faster and thereby decreases the time during which resistant mutants can arise, but increases the selective advantage of these mutants over wild-type cells. When competition for resources is weak, the former effect is dominant and greater synergy more effectively prevents multi-drug resistance. However, under conditions of strong resource competition, a tradeoff emerges in which greater synergy increases the rate of infection clearance, but also increases the risk of multi-drug resistance. This tradeoff breaks down at a critical level of drug interaction, above which greater synergy has no effect on infection clearance, but still increases the risk of multi-drug resistance. These results suggest that the optimal strategy for suppressing multi-drug resistance is not always to maximize synergy, and that in some cases drug antagonism, despite its weaker efficacy, may better suppress the evolution of multi-drug resistance. PMID:20532210

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

To address the limitations of traditional drug delivery, TiO 2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

2017-01-01

To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. PMID:28053530

Recent advances in the treatment of rheumatoid arthritis.

PubMed

Mahajan, Tina D; Mikuls, Ted R

2018-05-01

Therapies for rheumatoid arthritis (RA) continue to expand rapidly. The purpose of this review is to discuss novel treatment options, including biosimilars, that are available, as well as to highlight promising agents in development. The purpose is also to discuss new emerging safety signals associated with these drugs and to discuss strategies in tapering therapy. There are several novel RA therapies. These include the interleukin-6 (IL-6) receptor blocker sarilumab, which was approved in 2017. In aggregate, the sarilumab studies show that it is effective in RA, including patients with incomplete responses to methotrexate and anti-tumor necrosis factor inhibitor, and showing superior efficacy when used in higher dose (200 mg every 2 weeks) to standard-dose adalilumab. Other drugs that are currently being studied include the IL-6 cytokine blocker sarikumab, the small targeted molecule filgotinib, and many new biosimilars. Baracitinib failed to achieve approval by the Food and Drug Administration primarily over perceived safety concerns. The two biosimilar drugs currently approved are CT-P13 and SB2, which are based on the reference product infliximab. Although this review summarizes trials examining biologic tapering, additional data are needed to guide clinicians in regards to treatment de-escalation in RA. With the greatly expanded armamentarium of RA treatment options available, it is important for clinicians to understand the data regarding drug efficacy and safety. With remission increasingly attainable, effective drug tapering strategies are needed. Although tapering trials do exist, more studies will be needed to help guide clinical practice.

Improving drug delivery technology for treating neurodegenerative diseases.

PubMed

Choonara, Yahya E; Kumar, Pradeep; Modi, Girish; Pillay, Viness

2016-07-01

Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer's disease and Parkinson's disease. However, much work is still required in this field beyond the preclinical testing phase.

FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma

PubMed Central

Prowell, Tatiana M.; Ibrahim, Amna; Farrell, Ann T.; Justice, Robert; Mitchell, Shan Sun; Sridhara, Rajeshwari; Pazdur, Richard

2010-01-01

This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel®), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-α versus those receiving temsirolimus alone or in combination with IFN-α. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-α arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-α did not lead to a significant difference in OS compared with IFN-α alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-α arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-α and provides an additional treatment option for patients with advanced RCC. PMID:20332142

Drug Abuse: The Crack Cocaine Epidemic Health Consequences and Treatment.

DTIC Science & Technology

1991-01-01

addicts . Buackground Once considered to be nonaddictive, recent studies show that cocaine is one of the most potent drugs of abuse. Cocaine is a...responsibility for addiction prevention and treatment programs. The agencies we contacted include NIDA, the Alcohol, Drug Abuse, and Mental Health Administration...heroin addicts for Treating Crack are being used to treat many crack addicts . Meanwhile, drug treatment Addicts researchers are experimenting with new

Severity of club drug dependence and perceived need for treatment among a sample of adult club drug users in Shanghai, China

PubMed Central

Ding, Yingying; He, Na; Shoptaw, Steven; Gao, Meiyang; Detels, Roger

2013-01-01

Purpose Examine the severity of club drug dependence and perceived need for treatment, and further identify their determinants among a sample of club drug users in Shanghai, China. Methods 276 club drug users were recruited using respondent-driven sampling (RDS). Severity of dependence on club drugs was measured using the Severity of Dependence Scale (SDS). Results 69.9% reported dependence on club drugs (i.e., SDS≥4) and 36.6% reported severe dependence (i.e., SDS≥6). One eighth (12.7%) perceived need for drug treatment. Severe dependence on club drugs was more likely among those who reported recent use of ecstasy and those who had more depressive symptoms, but less likely among those reporting recent use of methamphetamine. Perceived need for treatment was more likely among those who lived with a spouse or boy/girlfriend, but less likely among those had prior drug treatment experience and more severe club drug dependence. Conclusions Our findings suggest that educational activities should be implemented to raise public awareness about the powerful addictive properties of club drugs, along with efforts to reduce stigma towards drug abuse and psychiatric disorders. Programs to motivate drug users to seek treatment and encourage treatment linkage are urgently needed. PMID:23715971

Bioresponsive polymer coated drug nanorods for breast cancer treatment

NASA Astrophysics Data System (ADS)

Laemthong, Tunyaboon; Kim, Hannah H.; Dunlap, Kelly; Brocker, Caitlin; Barua, Dipak; Forciniti, Daniel; Huang, Yue-Wern; Barua, Sutapa

2017-01-01

Ineffective drug release at the target site is among the top challenges for cancer treatment. This reflects the facts that interaction with the physiological condition can denature active ingredients of drugs, and low delivery to the disease microenvironment leads to poor therapeutic outcomes. We hypothesize that depositing a thin layer of bioresponsive polymer on the surface of drug nanoparticles would not only protect drugs from degradation but also allow the release of drugs at the target site. Here, we report a one-step process to prepare bioresponsive polymer coated drug nanorods (NRs) from liquid precursors using the solvent diffusion method. A thin layer (10.3 ± 1.4 nm) of poly(ε-caprolactone) (PCL) polymer coating was deposited on the surface of camptothecin (CPT) anti-cancer drug NRs. The mean size of PCL-coated CPT NRs was 500.9 ± 91.3 nm length × 122.7 ± 10.1 nm width. The PCL polymer coating was biodegradable at acidic pH 6 as determined by Fourier transform infrared spectroscopy. CPT drugs were released up to 51.5% when PCL coating dissolved into non-toxic carboxyl and hydroxyl groups. Trastuzumab (TTZ), a humanized IgG monoclonal antibody, was conjugated to the NR surface for breast cancer cell targeting. Combination treatments using CPT and TTZ decreased the HER-2 positive BT-474 breast cancer cell growth by 66.9 ± 5.3% in vitro. These results suggest effective combination treatments of breast cancer cells using bioresponsive polymer coated drug delivery.

Advanced drug delivery systems for antithrombotic agents

PubMed Central

Greineder, Colin F.; Howard, Melissa D.; Carnemolla, Ronald; Cines, Douglas B.

2013-01-01

Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena. PMID:23798715

Drug Treatment Centers in Afghanistan: Creating a Participatory Approach to Tackling the Drug Trade

DTIC Science & Technology

2012-12-01

Anti-Government Forces AIDS: Acquired Immunodeficiency Syndrome ANP: Afghan National Police ART: Anti-Retroviral Treatment BPHS: Basic Package of...treatment centers do performance reviews, corruption within the drug treatment clinics, and how management monitor staff burnout . While clinical governance

Meta-analyses of seven of the National Institute on Drug Abuse's principles of drug addiction treatment.

PubMed

Pearson, Frank S; Prendergast, Michael L; Podus, Deborah; Vazan, Peter; Greenwell, Lisa; Hamilton, Zachary

2012-07-01

Of the 13 principles of drug addiction treatment disseminated by the National Institute on Drug Abuse (NIDA), 7 were meta-analyzed as part of the Evidence-based Principles of Treatment (EPT) project. By averaging outcomes over the diverse programs included in the EPT, we found that 5 of the NIDA principles examined are supported: matching treatment to the client's needs, attending to the multiple needs of clients, behavioral counseling interventions, treatment plan reassessment, and counseling to reduce risk of HIV. Two of the NIDA principles are not supported: remaining in treatment for an adequate period and frequency of testing for drug use. These weak effects could be the result of the principles being stated too generally to apply to the diverse interventions and programs that exist or unmeasured moderator variables being confounded with the moderators that measured the principles. Meta-analysis should be a standard tool for developing principles of effective treatment for substance use disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

[Recent research advance on bone marrow microenvironment-mediated leukemia drug resistant mechanism].

PubMed

Fu, Bing; Ling, Yan-Juan

2011-06-01

The bone marrow microenvironment consists of bone marrow stromal cells, osteoblasts and osteoclasts which facilities the survival, differentiation and proliferation of hematopoietic cells through secreting soluble factors and extracellular matrix proteins that mediate these functions. This environment not only supports the growth of normal and malignant hematopoietic cells, but also protects them against the damage from chemotherapeutic agents through the secretion of soluble cytokines, cell adhesion, up-regulation of resistant genes and changes of cell cycle. In this review, the research advances on drug-resistance mechanisms mediated by bone marrow microenvironment are summarized briefly, including soluble factors mediating drug resistance, intercellular adhesion inducing drug resistance, up-regulation of some drug resistance genes, regulation in metabolism of leukemic cells, changes in cell cycles of tumor cells and so on.

Phycocyanin: A Potential Drug for Cancer Treatment

PubMed Central

Jiang, Liangqian; Wang, Yujuan; Yin, Qifeng; Liu, Guoxiang; Liu, Huihui; Huang, Yajing; Li, Bing

2017-01-01

Phycocyanin isolated from marine organisms has the characteristics of high efficiency and low toxicity, and it can be used as a functional food. It has been reported that phycocyanin has anti-oxidative function, anti-inflammatory activity, anti-cancer function, immune enhancement function, liver and kidney protection pharmacological effects. Thus, phycocyanin has an important development and utilization as a potential drug, and phycocyanin has become a new hot spot in the field of drug research. So far, there are more and more studies have shown that phycocyanin has the anti-cancer effect, which can block the proliferation of cancer cells and kill cancer cells. Phycocyanin exerts anti-cancer activity by blocking tumor cell cell cycle, inducing tumor cell apoptosis and autophagy, thereby phycocyanin can serve as a promising anti-cancer agent. This review discusses the therapeutic use of phycocyanin and focuses on the latest advances of phycocyanin as a promising anti-cancer drug. PMID:29151925

The First Decade of the National Drug Abuse Treatment Clinical Trials Network: Bridging the Gap Between Research and Practice to Improve Drug Abuse Treatment

PubMed Central

Tai, Betty; Straus, Michele M.; Liu, David; Sparenborg, Steven; Jackson, Ron; McCarty, Dennis

2010-01-01

The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to improve the quality of addiction treatment using science as the vehicle. The network brings providers from community-based drug abuse treatment programs and scientists from university-based research centers together in an alliance that fosters bi-directional communication and collaboration. Collaboration enhanced the relevance of research to practice and facilitated the development and implementation of evidence-based treatments in community practice settings. The CTN’s 20 completed trials tested pharmacological, behavioral, and integrated treatment interventions for adolescents and adults; more than 11,000 individuals participated in the trials. This paper reviews the rationale for the CTN, describes the translation of its guiding principles into research endeavors, and anticipates the future evolution of clinical research within the Network. PMID:20307794

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Novel drug target identification for the treatment of dementia using multi-relational association mining.

PubMed

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-07-08

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

Novel drug target identification for the treatment of dementia using multi-relational association mining

PubMed Central

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-01-01

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. PMID:26154857

Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

PubMed

Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

2013-11-18

Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis.

PubMed

Lou, Yan; Han, Xiaochun; Kuglstatter, Andreas; Kondru, Rama K; Sweeney, Zachary K; Soth, Michael; McIntosh, Joel; Litman, Renee; Suh, Judy; Kocer, Buelent; Davis, Dana; Park, Jaehyeon; Frauchiger, Sandra; Dewdney, Nolan; Zecic, Hasim; Taygerly, Joshua P; Sarma, Keshab; Hong, Junbae; Hill, Ronald J; Gabriel, Tobias; Goldstein, David M; Owens, Timothy D

2015-01-08

Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties.

Mental Health Status, Drug Treatment Use, and Needle Sharing among Injection Drug Users

ERIC Educational Resources Information Center

Lundgren, Lena M.; Amodeo, Maryann; Chassler, Deborah

2005-01-01

This study examined the relationship among mental health symptoms, drug treatment use, and needle sharing in a sample of 507 injection drug users (IDUs). Mental health symptoms were measured through the ASI psychiatric scale. A logistic regression model identified that some of the ASI items were associated with needle sharing in an opposing…

Dissolving microneedles for transdermal drug delivery: Advances and challenges.

PubMed

Ita, Kevin

2017-09-01

Over the last number of years, a significant body of evidence has shown the benefit of using dissolving microneedles (DMNs) for transdermal drug delivery. These devices are prepared from a wide range of materials such as sugars and polymers. DMNs are mainly fabricated by micromolding, photopolymerization, drawing lithography and droplet-airborne blowing. In this review, we have focused on the advances made in the field in recent years using a representative set of studies. Although the list of studies is not exhaustive, they highlight the challenges encountered such as the need to increase mechanical strength as well as medication dose while ensuring fast release of the active ingredient. DMNs can be used to delivery low molecular drugs as well as peptides, proteins and other high molecular weight compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration.

PubMed

Petrovic, Mira; de Alda, Maria Jose Lopez; Diaz-Cruz, Silvia; Postigo, Cristina; Radjenovic, Jelena; Gros, Meritxell; Barcelo, Damià

2009-10-13

Pharmaceutically active compounds (PhACs) and drugs of abuse (DAs) are two important groups of emerging environmental contaminants that have raised an increasing interest in the scientific community. A number of studies revealed their presence in the environment. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, being able to reach surface and groundwater and subsequently, drinking waters. This paper reviews the data regarding the levels of pharmaceuticals and illicit drugs detected in wastewaters and gives an overview of their removal by conventional treatment technologies (applying activated sludge) as well as advanced treatments such as membrane bioreactor. The paper also gives an overview of bank filtration practices at managed aquifer recharge sites and discusses the potential of this approach to mitigate the contamination by PhACs and DAs.

Treatment of non-steroidal anti-inflammatory drug induced enteropathy.

PubMed Central

Bjarnason, I; Hopkinson, N; Zanelli, G; Prouse, P; Smethurst, P; Gumpel, J M; Levi, A J

1990-01-01

Non-steroidal anti-inflammatory drug induced small intestinal inflammation may have an adverse effect on the joints of patients with rheumatoid arthritis. We therefore assessed small intestinal and joint inflammation in patients with rheumatoid arthritis before and after three to nine months' treatment with sulphasalazine (n = 40) and other second line drugs (n = 20), while keeping the dosage of non-steroidal anti-inflammatory drug at the same level. Sulphasalazine significantly decreased the mean (SD) faecal excretion of 111indium labelled leucocytes from 2.39 (2.22)% to 1.33 (1.13)% (normal less than 1%, p less than 0.01) and improved the joint inflammation as assessed by a variety of parameters. There was no significant correlation between the effects of sulphasalazine treatment on the intestine and the joints. Treatment with other second line drugs had no significant effect on the faecal excretion of 111indium (1.58 (1.04)% and 1.86 (1.51)%, respectively) but improved joint inflammation significantly. The lack of correlation between the intestinal and joint inflammation and their response to treatment suggests that the two are not causally related. PMID:1973396

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

PubMed Central

Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

2014-01-01

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

Laboratory diagnosis of tuberculosis: Advances in technology and drug susceptibility testing.

PubMed

Oommen, Seema; Banaji, Nandita

2017-01-01

There have been rapid technological advances in the detection of Mycobacterium tuberculosis and its drug susceptibility in clinical samples. These include advances in microscopic examination, in vitro culture and application of molecular techniques. The World Health Organization (WHO) has played a large role in evaluating these technologies for their efficacy and feasibility, especially in the developing countries. Amongst these, the Revised National Tuberculosis Control Programme (RNTCP), through its national network of designated microscopy centres and intermediate reference laboratories, has adopted certain technologies that are currently implemented in India. Advances in microscopy technology include fluorescent microscopy using light-emitting diode source, sodium hypochlorite microscopy and vital fluorescent staining of sputum smears. Automation of in vitro culture has markedly reduced the turnaround time (TAT), even in smear-negative samples, and permits simultaneous detection of resistant mutants. Molecular detection of drug resistance has further reduced the TAT, and the cartridge-based nucleic acid amplification test with its performance convenience and rapid results, appears poised to become the future of tuberculosis (TB) diagnosis in all settings, provided the cost of testing is reduced especially for use in private diagnostic settings. This article reviews technologies currently available for the diagnosis of TB, keeping in mind the WHO recommendations and the RNTCP practices. This is a thematic synthesis of data available on diagnosis in literature, preserving the conclusions of the primary studies.

Therapeutic community drug treatment success in Peru: a follow-up outcome study

PubMed Central

Johnson, Knowlton; Pan, Zhenfeng; Young, Linda; Vanderhoff, Jude; Shamblen, Steve; Browne, Thom; Linfield, Ken; Suresh, Geetha

2008-01-01

Background The purpose of this study was to assess the impact of drug abuse treatment in Peru that used the therapeutic community (TC) model. Program directors and several staff members from all study treatment facilities received two to eight weeks of in-country training on how to implement the TC treatment model prior to the follow-up study. Methods This outcome study involved 33 TC treatment facilities and 509 former clients in Lima and other cities in five providences across Peru. A retrospective pre-test (RPT) follow-up design was employed in which 30-day use of illegal drugs and alcohol to intoxication was measured at baseline retrospectively, at the same time of the six-month follow-up. In-person interview data were collected from directors of 73 percent of the eligible TC organizations in January and February 2003 and from former 58 percent of the eligible TC former clients between October 2003 and October 2004. Drug testing was conducted on a small sample of former clients to increase the accuracy of the self-reported drug use data. Results Medium to large positive treatment effects were found when comparing 30-day illegal drug and alcohol use to intoxication before and six months after receiving treatment. As a supplemental analysis, we assumed the 42 percent of the former clients who were not interviewed at the six month assessment had returned to drugs. These results showed medium treatment effects as well. Hierarchical Generalized Linear Modeling (HGLM) results showed higher implementation fidelity, less stigma after leaving treatment, and older clients, singly or in combination are key predictors of treatment success. Conclusion This study found that former clients of drug and alcohol treatment in facilities using the TC model reported substantial positive change in use of illegal drugs and alcohol to intoxication at a six-month follow-up. The unique contribution of this study is that the results also suggest attention should be placed on the

Effects of Motivation and Problem Severity on Court-Based Drug Treatment

ERIC Educational Resources Information Center

Cosden, Merith; Basch, Janice E.; Campos, Emily; Greenwell, Ashley; Barazani, Sivan; Walker, Sara

2006-01-01

This study addresses the effects of motivation and problem severity on outcomes in two court-based drug treatment programs. Data were examined for 578 offenders served by a drug court and 223 served by a drug treatment court mandated through California's Substance Abuse Crime Prevention Act (SACPA). It was hypothesized that client-reported…

Treatment Services for Drug Dependent Women. Volume 1. Treatment Research Monograph Series.

ERIC Educational Resources Information Center

Beschner, George M., Ed.; And Others

This book is the first of two volumes designed to highlight and integrate current knowledge about drug dependent women, with a focus on needed services and appropriate delivery systems, as well as to provide useful information for counselors and treatment program developers. The special problems, needs, and characteristics of women drug abusers…

Interstitial laser photochemotherapy with new anthrapyrazole drugs for the treatment of xenograft tumors.

PubMed

Paiva, M B; Saxton, R E; Letts, G A; Chung, P S; Soudant, J; Vanderwerf, Q; Castro, D J

1995-10-01

Photodynamic therapy (PDT) with lasers and new dyes has gained popularity in recent years as a minimally invasive technique with high tumoricidal effects in vitro and in some cancer patients. However, because new laser dyes are not FDA approved at present, the clinical evaluation of PDT may be years away. During the past 6 years we have used laser alone for photothermal ablation in both preclinical studies and in a large number of patients with an observed 60% tumor response rate. The 40% treatment failure led us to explore the possibility of combined therapy with lasers and standard chemotherapeutic drugs. We have recently tested a promising preclinical alternative using implantation of a bare 600-microns KTP 532 laser fiberoptic in multiple tumor sites 30 min after intratumor injection of the anthrapyrazole DUP-941. As a control, this drug was injected in 3 sites of P3 human squamous cell tumor transplants in nude mice, which led to tumor stasis without regression. Similar 400-600 mm3 tumors exposed to laser illumination alone (0.8 W for 5 sec) at multiple sites resulted in tumor regrowth after 10 weeks in 80% of the animals. However, combining interstitial laser illumination with intratumor DUP-941 injections led to complete tumor regression in 85% of the mice. We propose that intratumor drug injection followed by interstitial laser fiberoptic treatment represents a potentially useful new method for tumor ablation in advanced cancer patients.

Drug Repositioning for Effective Prostate Cancer Treatment.

PubMed

Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil

2018-01-01

Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

PubMed Central

Kesharwani, Prashant; Iyer, Arun K.

2015-01-01

Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

Gender differences among prisoners in drug treatment.

PubMed

Langan, N P; Pelissier, B M

2001-01-01

Nearly all prison-based substance abuse treatment programs have been designed with male prisoners in mind. Administering these male-oriented programs to women prisoners has been the standard correctional practice. Recently, this practice has received considerable criticism. Critics argue that female prisoners have special needs that are not met by programs originally designed for male prisoners. However, most of the empirical support for the existence of such special needs rely on two inappropriate samples: prisoners who are not in treatment and treatment participants who are not incarcerated. Findings from these two different groups may not be generalizable to the population of prisoners in treatment. This paper directly addresses this generalizability problem with an examination of gender differences among 1,326 male and 318 female federal prisoners who were enrolled in a substance abuse treatment program. Women used drugs more frequently, used harder drugs, and used them for different reasons than men. Women also confronted more difficulties than men in areas linked to substance abuse such as educational background, childhood family environment, adult social environment, mental health, and physical health. We find support for the argument that substance abuse treatment programs which were originally designed for men may be inappropriate for the treatment of women.

MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases.

PubMed

Dua, Kamal; Hansbro, Nicole G; Foster, Paul S; Hansbro, Philip M

2017-02-01

The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

PubMed

Sicherer, Scott H; Leung, Donald Y M

2012-01-01

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

[Routine chemotherapeutic drug treatment effectiveness predictive molecules and chemotherapeutic drug selection].

PubMed

Zhao, Xiao-Dong; Zhang, Yi

2006-12-01

Drug selection, the key for chemotherapy, is one of the most difficult decision-making in clinic for the treatment of malignant tumors. How to choose is undetermined. Here a new strategy--predictive molecule-targeted chemotherapy (PMTC)--is put forward to choose relatively sensitive chemotherapeutic drugs and to avoid relatively resistant traditional drugs according to the expression of predictive molecules in individual tumor tissue. For example, paclitaxel is regarded as a relatively sensitive drug and may be chosen for the tumors with high expression of p53, while it is predicted as relatively resistant drug and should be avoided for the tumors with high expression of P-glycoprotein (P-gp). Here, we reviewed the predictive values of a variety of molecules, such as p53, P-gp, topoisomerase-1, topoisomerase-2, MSI, BRCA-1, ERCC1, FANC, hMHL1/2, XPD, Bcl-2, ErbB-2, MGMT, dihydropyridine dehydrogenase (DPD), thymidylate synthetase (TS), deoxycytidine kinase (dCK), Ras, Bax, Cyclin A, tubulin proteins, and so on, for the efficacy of some traditional chemotherapeutic drugs, such as platinum, oxaliplatin, cyclophosphamide, ifosfamide, dacarbazine, methotrexate, 5-flurouracil, gemcitabine, vincristine, vinorelbine, paclitaxel, etoposide, irinotecan, topotecan, and so on.

[Development of performance evaluation and management system on advanced schistosomiasis medical treatment].

PubMed

Zhou, Xiao-Rong; Huang, Shui-Sheng; Gong, Xin-Guo; Cen, Li-Ping; Zhang, Cong; Zhu, Hong; Yang, Jun-Jing; Chen, Li

2012-04-01

To construct a performance evaluation and management system on advanced schistosomiasis medical treatment, and analyze and evaluate the work of the advanced schistosomiasis medical treatment over the years. By applying the database management technique and C++ programming technique, we inputted the information of the advanced schistosomiasis cases into the system, and comprehensively evaluated the work of the advanced schistosomiasis medical treatment through the cost-effect analysis, cost-effectiveness analysis, and cost-benefit analysis. We made a set of software formula about cost-effect analysis, cost-effectiveness analysis, and cost-benefit analysis. This system had many features such as clear building, easy to operate, friendly surface, convenient information input and information search. It could benefit the performance evaluation of the province's advanced schistosomiasis medical treatment work. This system can satisfy the current needs of advanced schistosomiasis medical treatment work and can be easy to be widely used.

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

PubMed

Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

2018-04-05

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Advances in the diagnosis and treatment of fungal infections of the CNS.

PubMed

Schwartz, Stefan; Kontoyiannis, Dimitrios P; Harrison, Thomas; Ruhnke, Markus

2018-04-01

Fungal infections of the CNS are challenging to treat and their optimal management requires knowledge of their epidemiology, host characteristics, diagnostic criteria, and therapeutic options. Aspergillus and Cryptococcus species predominate among fungal infections of the CNS. Most of these fungi are ubiquitous, but some have restricted geographical distribution. Fungal infections of the CNS usually originate from primary sites outside the CNS (eg, fungal pneumonia) or occur after inoculation (eg, invasive procedures). Most patients with these infections have immunodeficiencies, but immunocompetent individuals can also be infected through heavy exposure. The infecting fungi can be grouped into moulds, yeasts, and dimorphic fungi. Substantial progress has been made with new diagnostic approaches and the introduction of novel antifungal drugs, but fungal infections of the CNS are frequently lethal because of diagnostic delays, impaired drug penetration, resistance to antifungal treatments, and inadequate restoration of immune function. To improve outcomes, future research should advance diagnostic methods (eg, molecular detection and fungus identification), develop antifungal compounds with enhanced CNS-directed efficacy, and further investigate crucial host defence mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

[The role of meta-analysis in assessing the treatment of advanced non-small cell lung cancer].

PubMed

Pérol, M; Pérol, D

2004-02-01

Meta-analysis is a statistical method allowing an evaluation of the direction and quantitative importance of a treatment effect observed in randomized trials which have tested the treatment but have not provided a definitive conclusion. In the present review, we discuss the methodology and the contribution of meta-analyses to the treatment of advanced-stage or metastatic non-small-cell lung cancer. In this area of cancerology, meta-analyses have provided determining information demonstrating the impact of chemotherapy on patient survival. They have also helped define a two-drug regimen based on cisplatin as the gold standard treatment for patients with a satisfactory general status. Recently, the meta-analysis method was used to measure the influence of gemcitabin in combination with platinium salts and demonstrated a small but significant benefit in survival, confirming that gemcitabin remains the gold standard treatment in combination with cisplatin.

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

PubMed Central

Yang, Conglian; Wu, Tingting; Qi, Yan; Zhang, Zhiping

2018-01-01

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future. PMID:29290821

Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment.

PubMed

Lange, Christoph; Chesov, Dumitru; Heyckendorf, Jan; Leung, Chi C; Udwadia, Zarir; Dheda, Keertan

2018-04-11

The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure. © 2018 Asian Pacific Society of Respirology.

Drug treatment in patients with newly diagnosed unprovoked seizures/epilepsy.

PubMed

Karlsson, Linnéa; Wettermark, Björn; Tomson, Torbjörn

2014-07-01

The objective of this study was to analyze drug treatment in patients with newly diagnosed unprovoked seizures/epilepsy in a population-based cohort in Stockholm, Sweden. Clinical data from the Stockholm Incidence Registry of Epilepsy was cross-linked with drug dispensing data from the Swedish Prescribed Drug Register to analyze drug treatment in patients diagnosed with unprovoked seizures between 2006 and 2008. Specific questions addressed were the use of other medications at seizures onset, the proportion of patients initiated on different antiepileptic drugs (AEDs) within one year after inclusion, and the extent of switching between different AEDs during the first year. In total 367 patients were included. More than 50% had other medications prescribed at date of first seizure. All together, 262 patients received an AED within one year and 257 patients (98%) were initiated on monotherapy. One year after first prescription, 147 patients (56%) remained on the initially prescribed AED and 48 patients (18%) had switched to another AED. Among the remaining patients, 29 (11%) had died and 38 patients (15%) had discontinued AED treatment. A majority of all patients with epilepsy receive treatment within one year. Many patients use other medications and several of them are related to known comorbidities and can also be involved in drug-drug interactions. Nevertheless, most patients remained on the same AED at the end of the first year. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

PubMed

Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

Natural Product-Derived Drugs for the Treatment of Inflammatory Bowel Diseases

PubMed Central

2014-01-01

Natural products have been used as drugs for millennia, and the therapeutic potential of natural products has been studied for more than a century. Since the mid-1880s, approximately 60% of drugs have originated from natural products. Recently, the importance of using natural products has increased, as has interest in discovering efficient new drugs. Natural drugs are desirable for the treatment of inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. This review discusses the discovery and development of drugs derived from natural products for the treatment of inflammatory bowel diseases. PMID:25349576

The impact of the Orphan Drug Act on drug discovery.

PubMed

Haffner, Marlene E; Maher, Paul D

2006-11-01

For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

Bevacizumab improves survival for patients with advanced cervical cancer

Cancer.gov

Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.

PubMed

Knickelbein, Jared E; Jacobs-El, Naima; Wong, Wai T; Wiley, Henry E; Cukras, Catherine A; Meyerle, Catherine B; Chew, Emily Y

2017-01-01

medications in the same class or drugs directed at multiple targets in the tumor, may be safer and more effective for the treatment of advanced VHL-associated RCH.

Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease

PubMed Central

Knickelbein, Jared E.; Jacobs-El, Naima; Wong, Wai T.; Wiley, Henry E.; Cukras, Catherine A.; Meyerle, Catherine B.; Chew, Emily Y.

2016-01-01

medication used at lower doses with different treatment strategies, other medications in the same class or drugs directed at multiple targets in the tumor, may be safer and more effective for the treatment of advanced VHL-associated RCH. PMID:28670632

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Explanations and expectations: drug narratives among young cannabis users in treatment

PubMed Central

Järvinen, Margaretha; Ravn, Signe

2015-01-01

This article analyses how young people enrolled in drug addiction treatment in Copenhagen, Denmark, explain their cannabis careers and how they view their possibilities for quitting drug use again. Inspired by Mead and narrative studies of health and illness, the article identifies four different drug use ‘aetiologies’ drawn upon by the interviewees. These cover childhood experiences, self-medication, the influence of friends and cannabis use as a specific lifestyle. A central argument of the article is that these explanations not only concern the past but also point towards the future by assigning the interviewee a more or less agential position in relation to drugs. Further, the drug narratives are viewed as interactional achievements, related to the social context in which they were produced, namely, the institutional setting of the treatment centres. The article is based on 30 qualitative interviews with young people in drug addiction treatment. PMID:25688710

Depression in adults: drug and physical treatments.

PubMed

Cipriani, Andrea; Barbui, Corrado; Butler, Rob; Hatcher, Simon; Geddes, John

2011-05-25

Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies. In severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in mild to moderate and severe depression, and in treatment-resistant depression? Which interventions reduce relapse rates? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 88 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressant drugs (tricyclic antidepressants [including low-dose tricyclic antidepressants], selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or venlafaxine), continuing prescription antidepressant drugs, electroconvulsive therapy, exercise, lithium augmentation, pindolol augmentation, and St John's wort.

Depression in adults: drug and physical treatments.

PubMed

Barbui, Corrado; Butler, Rob; Cipriani, Andrea; Geddes, John; Hatcher, Simon

2007-06-15

Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies. In severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in mild to moderate and severe depression, and in treatment-resistant depression? Which interventions reduce relapse rates? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 87 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressant drugs (tricyclic antidepressants [including low-dose tricyclic antidepressants], selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, reboxetine, or venlafaxine), continuing prescription antidepressant drugs, electroconvulsive therapy, exercise, lithium augmentation, pindolol augmentation, St John's Wort.

Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

PubMed

Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

2017-01-01

Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Audits for advanced treatment dosimetry

NASA Astrophysics Data System (ADS)

Ibbott, G. S.; Thwaites, D. I.

2015-01-01

Radiation therapy has advanced rapidly over the last few decades, progressing from 3D conformal treatment to image-guided intensity modulated therapy of several different flavors, both 3D and 4D and to adaptive radiotherapy. The use of intensity modulation has increased the complexity of quality assurance and essentially eliminated the physicist's ability to judge the validity of a treatment plan, even approximately, on the basis of appearance and experience. Instead, complex QA devices and procedures are required at the institutional level. Similarly, the assessment of treatment quality through remote and on-site audits also requires greater sophistication. The introduction of 3D and 4D dosimetry into external audit systems must follow, to enable quality assurance systems to perform meaningful and thorough audits.

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

PubMed Central

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

PubMed

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

Ocular drug delivery systems: An overview

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Ocular drug delivery systems: An overview.

PubMed

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

PubMed

Sicherer, Scott H; Leung, Donald Y M

2010-01-01

This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.