Treating Women Drug Abusers: Action Therapy and Trauma Assessment

Science.gov (United States)

Uhler, Ann S.; Parker, Olga V.

2002-01-01

The authors suggest that action therapy, a group of techniques including psychodrama, drama therapy, and role training, warrants research attention to determine whether it is well suited to the special characteristics and needs of women clients. In addition, the authors call on researchers to develop a new standardized tool for counselors to use during initial interviews to determine whether women presenting for drug abuse treatment also have significant issues related to trauma. The authors believe the use of unassisted clinical judgment for trauma assessment in first interviews may drive patients away by probing for painful information that clients are not yet ready to confront or divulge. PMID:18567963

Estimation of the standardized risk difference and ratio in a competing risks framework: application to injection drug use and progression to AIDS after initiation of antiretroviral therapy.

Science.gov (United States)

Cole, Stephen R; Lau, Bryan; Eron, Joseph J; Brookhart, M Alan; Kitahata, Mari M; Martin, Jeffrey N; Mathews, William C; Mugavero, Michael J

2015-02-15

There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

Directory of Open Access Journals (Sweden)

Jan eStenvang

2013-12-01

Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

Potential drug therapies for the treatment of fibromyalgia.

Science.gov (United States)

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.

Drug therapy smartens up

Science.gov (United States)

Martin, Christian

2015-11-01

The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

Science.gov (United States)

Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

2016-05-26

The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

Metabolomics has the potential to improve drug therapy

DEFF Research Database (Denmark)

Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

2014-01-01

Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

75 FR 15440 - Guidance for Industry on Standards for Securing the Drug Supply Chain-Standardized Numerical...

Science.gov (United States)

2010-03-29

...] Guidance for Industry on Standards for Securing the Drug Supply Chain--Standardized Numerical... industry entitled ``Standards for Securing the Drug Supply Chain-Standardized Numerical Identification for... the Drug Supply Chain-Standardized Numerical Identification for Prescription Drug Packages.'' In the...

Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

Science.gov (United States)

Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

2016-04-07

New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb m

Population-based differences in treatment outcome following anticancer drug therapies.

Science.gov (United States)

Ma, Brigette By; Hui, Edwin P; Mok, Tony Sk

2010-01-01

Population-based differences in toxicity and clinical outcome following treatment with anticancer drugs have an important effect on oncology practice and drug development. These differences arise from complex interactions between biological and environmental factors, which include genetic diversity affecting drug metabolism and the expression of drug targets, variations in tumour biology and host physiology, socioeconomic disparities, and regional preferences in treatment standards. Some well-known examples include the high prevalence of activating epidermal growth factor receptor (EGFR) mutations in pulmonary adenocarcinoma among northeast (China, Japan, Korea) and parts of southeast Asia (excluding India) non-smokers, which predict sensitivity to EGFR kinase inhibitors, and the sharp contrast between Japan and the west in the management and survival outcome of gastric cancer. This review is a critical overview of population-based differences in the four most prevalent cancers in the world: lung, breast, colorectal, and stomach cancer. Particular attention is given to the clinical relevance of such knowledge in terms of the individualisation of drug therapy and in the design of clinical trials. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Laboratory markers in personalized drug therapy

NARCIS (Netherlands)

Geerts, A.F.J.

2012-01-01

During the last decade two major trends have influenced the thinking about the benefit-risk balance in drug therapy.The first trend showed that this balance is not only determined by the interaction of the pharmacological properties of the drug with the patient’s (patho)physiological profile, but is

Nanomaterials potentiating standard chemotherapy drugs' effect

Science.gov (United States)

Kazantsev, S. O.; Korovin, M. S.

2017-09-01

Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

Spiritual self-schema therapy, drug abuse, and HIV.

Science.gov (United States)

Marcotte, David; Avants, S Kelly; Margolin, Arthur

2003-01-01

This case report describes the use of Spiritual Self-Schema (3-S) therapy in the treatment of an HIV-positive inner-city drug user maintained on methadone and referred for additional treatment due to unremitting cocaine use. 3-S therapy is a manual-guided intervention based on cognitive self-schema theory. Its goal is to help the patient create, elaborate, and make accessible a cognitive schema--the "spiritual" self-schema-that is incompatible with drug use and other HIV risk behaviors. 3-S therapy facilitates a cognitive shift from the habitual activation of the "addict" self-schema, with its drug-related cognitions, scripts and action plans, to the "spiritual" self-schema, with its associated repertoire of harm reduction beliefs and behaviors.

Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

Science.gov (United States)

Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

2016-10-28

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

Science.gov (United States)

Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

2014-11-01

Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Methadone maintenance therapy as evidence based drug abuse ...

African Journals Online (AJOL)

Methadone maintenance therapy as evidence based drug abuse planning in ... drugs are being used as artificial problem-solvers such as frustrations, stress or ... Drug use is a problem to users when it begins to cause some damage to their ...

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

Science.gov (United States)

de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

Science.gov (United States)

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

Science.gov (United States)

Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

2018-08-01

Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

49 CFR 219.701 - Standards for drug and alcohol testing.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions

NARCIS (Netherlands)

Burger, D.M.; Back, D.; Buggisch, P.; Buti, M.; Craxi, A.; Foster, G.; Klinker, H.; Larrey, D.; Nikitin, I.; Pol, S. van der; Puoti, M.; Romero-Gomez, M.; Wedemeyer, H.; Zeuzem, S.

2013-01-01

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the

Drug therapy in patients with Parkinson’s disease

Directory of Open Access Journals (Sweden)

Müller Thomas

2012-05-01

Full Text Available Abstract Parkinson`s disease (PD is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.

Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.

Science.gov (United States)

Panebianco, Concetta; Andriulli, Angelo; Pazienza, Valerio

2018-05-22

Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.

Fluorescent standards for photodynamic therapy

Science.gov (United States)

Belko, N.; Kavalenka, S.; Samtsov, M.

2016-08-01

Photodynamic therapy is an evolving technique for treatment of various oncological diseases. This method employs photosensitizers - species that lead to death of tumor cells after the photoactivation. For further development and novel applications of photodynamic therapy new photosensitizers are required. After synthesis of a new photosensitizer it is important to know its concentration in different biological tissues after its administration and distribution. The concentration is frequently measured by the extraction method, which has some disadvantages, e.g. it requires many biological test subjects that are euthanized during the measurement. We propose to measure the photosensitizer concentration in tissue by its fluorescence. For this purpose fluorescent standards were developed. The standards are robust and simple to produce; their fluorescence signal does not change with time. The fluorescence intensity of fluorescent standards seems to depend linearly on the dye concentration. A set of standards thus allow the calibration of a spectrometer. Finally, the photosensitizer concentration can be determined by the fluorescence intensity after comparing the corresponding spectrum with spectra of the set of fluorescent standards. A biological test subject is not euthanized during this kind of experiment. We hope this more humane technique can be used in future instead of the extraction method.

Comparison of Sequential Regimen and Standard Therapy for Helicobacter pylori Eradication in Patients with Dyspepsia

Directory of Open Access Journals (Sweden)

Gh. Roshanaei

2013-10-01

Full Text Available Introduction & Objective: Some studies have reported successful eradication rates using se-quential therapy but more recent studies performed in Asia did not find a similar benefit. Due to inconsistencies in the comparison of standard triple drugs therapy and sequential regimen, in the previous researches we decided to compare these treatments in Persian patients. Materials & Methods: This study is a randomized clinical trial, performed in one hundred and forty patients suffering from dyspepsia with indication for H. pylori eradication between No-vember 2010 and March 2012.Patients were randomized in two equal groups. The patients in the first group (standard were treated by omeprazole capsule 20 mg BID, amoxicillin cap-sule 1 gr BID, clarithromycin tablet 500mg BID for 14 days; while the patients in the second group (sequential were treated by omeprazole capsule 20 mg for 10 days, amoxicillin cap-sule 1 gr BID for 5 days, then clarithromycin tablet 500 mg and tinidazole tablet 500 mg BID for other 5 days. 4-6 weeks after the treatment, we compared the eradication of H.pylori be-tween the two groups by urease breathe test with C14. Results: H. pylori infection was successfully cured in 57/70 (81.43% with a 10-day sequen-tial therapy, in 60/70 (85.75% with the standard fourteen-day triple therapy, respectively. Conclusion: We detected no significant differences between the 10-day sequential eradication therapy for H. pylori and 14-day standard triple treatment among the patients. (Sci J Hamadan Univ Med Sci 2013; 20 (3:184-193

Targeted drugs in radiation therapy

International Nuclear Information System (INIS)

Favaudon, V.; Hennequin, C.; Hennequin, C.

2004-01-01

New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

The therapy of kidney cancer with biomolecular drugs.

Science.gov (United States)

Di Lorenzo, G; Buonerba, C; Biglietto, M; Scognamiglio, F; Chiurazzi, B; Riccardi, F; Cartenì, G

2010-11-01

Over the last few years, targeted agents have assumed a predominant role in treatment of metastatic renal cell carcinoma (mRCC). Our aim is to discuss recent developments on this rapidly evolving topic. Sunitinib represents front-line standard treatment for the good- and intermediate prognosis groups of patients with clear cell renal carcinoma. Bevacizumab/interferon and pazopanib have also been FDA-approved as first-line agents, while sorafenib has moved toward second-line and later therapy. Temsirolimus, an mTOR inhibitor, is recommended as front line therapy for patients in the poor-risk group and is the best front-line choice for patients with non-clear cell histology. Another mTOR inhibitor, everolimus, has shown clinical benefit post-tyrosine kinasis inhibitors failure in a phase III study and is considered the standard of care in this setting. Novel prognostic and efficacy markers might help to define most appropriate therapeutic strategy. Best sequence of use of these effective agents in mRCC patients remains up to the discretion of treating physician. In light of the considerable advances in understanding the biology of mRCC, several new drugs have been recently developed, with an increasing number of treatment options. Several markers are under evaluation for diagnostic, prognostic and efficacy purposes. A treatment algorithm, based on the best scientific evidence produce so far, is presented and it will evolve as data from ongoing trials will be available. Copyright © 2010 Elsevier Ltd. All rights reserved.

Alternative Drugs in Pain Therapy

Directory of Open Access Journals (Sweden)

İlker Kelle

2006-01-01

Full Text Available Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, renal failure and gastrointestinal bleeding. As a consequent, developing new forms of pain relievers that are more safe and effective without any other side effects has became the main goal of researchers. In recent studies, it has been shown that conotoxin therapies are not addictive, and have tolerable indexes unlike opioids. In addition, conotoxins side effects are much milder and easier to manage than those of opioids. In this regard, it has been emphasized that biotoxins such as conotoxins obtained from marine creatures can be better choices in pain management for future prospects.

Regional Lymphotropic Therapy in Combination with Low Level Laser Therapy for Treating Multi-Drug-Resistant Tuberculosis

Directory of Open Access Journals (Sweden)

Oksana Dogorova

2016-03-01

Full Text Available With the growing incidence of Multi-Drug-Resistant Tuberculosis (MDR-TB in newly identified patients, novel multimodality treatment methods are needed, aimed at reducing the time to sputum conversion and cavity healing, which would be applicable in MDR cases. Our experimental treatment consisted of the following: 1 chemotherapy based on the drug sensitivity profile, 2 local laser irradiation therapy for 25 days, and lymphotropic administration of isoniazid (to subcutaneous tissue in alternating locations: underarm area; fifth intercostal space along the sterna border; subclavian area where the first rib meets the sternum in a daily dose of 10mg/kg 5 times a week. This treatment was significantly more effective in newly detected destructive MDR-TB versus the standard Category IV regimen for MDR-TB in terms of reduced time for sputum culture conversion and cavity healing, estimated to be 6 months after initiation of treatment.

DNA nanostructure-based drug delivery nanosystems in cancer therapy.

Science.gov (United States)

Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

2017-11-25

DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

Science.gov (United States)

Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

2015-03-01

Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

Drug Therapy Problems in Patients on Antihypertensives and ...

African Journals Online (AJOL)

Drug therapy problems (DTPs), with the associated risks inherent in antihypertensive and antidiabetic therapy require utmost attention. This present study was aimed at assessing the DTPs observed in the management of hypertension and diabetes mellitus (DM) in two tertiary health facilities in Niger Delta region. In this ...

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

Science.gov (United States)

Cheng, Aristine; Chuang, Yu-Chung; Sun, Hsin-Yun; Sheng, Wang-Huei; Yang, Chia-Jui; Liao, Chun-Hsing; Hsueh, Po-Ren; Yang, Jia-Ling; Shen, Ni-Jiin; Wang, Jann-Tay; Hung, Chien-Ching; Chen, Yee-Chun; Chang, Shan-Chwen

2015-06-01

Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Prospective, observational, multicenter study. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline

Smart Drug Delivery Systems in Cancer Therapy.

Science.gov (United States)

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

Science.gov (United States)

Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

2013-06-01

In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

Bone scintigraphy during therapy with cytostatically acting drugs

International Nuclear Information System (INIS)

Schmidt, U.; Pries, H.H.; Joseph, K.; Mahlstedt, J.; Marburg Univ.

1976-01-01

Case reports show up, that bone scintigraphy during therapy of metastasing cancer of mamma or prostata with cytostatically acting drugs may reveal 'pseudonormal' results. False negative diagnosis can be excluded only by carefully regarding drug history. Gamma-camera with wholebody scan device for scintigraphy in two projections simplifies safe evaluation significantly. (orig.) [de

Standardization of 131I therapy for Graves disease

International Nuclear Information System (INIS)

Tang Jianlin; Li Yuying; Gao Liuyan; Tang Xiuping; Hu Hongyong

2011-01-01

Objective: To establish the normative and standard measures, to ensure medical safety and quality of care of the patients with Graves disease treated by 131 I therapy. Methods: Formulating and strictly implementing the medical organizational and technical measures of 131 I therapy for Graves disease and regular follow-up. Results: Receiving 131 I treatment of 104 patients, follow-up 6-36 months, no adverse events, the cure rate of 59.6%, the efficient rate is 99.9%. Conclusion: It is important guarantee for the medical quality and safety to standardize the 131 I therapy of Graves disease. (authors)

Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

Science.gov (United States)

Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

2017-01-01

Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

Directory of Open Access Journals (Sweden)

Cai Huang

Full Text Available Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM algorithm combined with a standard recursive feature elimination (RFE approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60. The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

Rational drug therapy education in clinical phase carried out by task-based learning

Science.gov (United States)

Bilge, S. Sırrı; Akyüz, Bahar; Ağrı, Arzu Erdal; Özlem, Mıdık

2017-01-01

Objectives: Irrational drug use results in drug interactions, treatment noncompliance, and drug resistance. Rational pharmacotherapy education is being implemented in many faculties of medicine. Our aim is to introduce rational pharmacotherapy education by clinicians and to evaluate task-based rational drug therapy education in the clinical context. Methods: The Kirkpatrick's evaluation model was used for the evaluation of the program. The participants evaluated the program in terms of constituents of the program, utilization, and contribution to learning. Voluntary participants responded to the evaluation forms after the educational program. Data are evaluated using both quantitative and qualitative tools. SPSS (version 21) used for quantitative data for determining mean and standard deviation values. Descriptive qualitative analysis approach is used for the analysis of open-ended questions. Results: It was revealed that the program and its components have been favorable. A total 95.9% of the students consider the education to be beneficial. Simulated patients practice and personal drug choice/problem-based learning sessions were appreciated by the students in particular. 93.9% of the students stated that all students of medicine should undergo this educational program. Among the five presentations contained in the program, “The Principles of Prescribing” received the highest points (9 ± 1.00) from participating students in general evaluation of the educational program. Conclusion: This study was carried out to improve task-based rational drug therapy education. According to feedback from the students concerning content, method, resource, assessment, and program design; some important changes, especially in number of facilitators and indications, are made in rational pharmacotherapy education in clinical task-based learning program. PMID:28458432

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

Science.gov (United States)

Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

2010-01-25

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

International Nuclear Information System (INIS)

Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

2017-01-01

The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m"2 of cisplatin and 30 mg/m"2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

Science.gov (United States)

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

Directory of Open Access Journals (Sweden)

Prisco L

2011-08-01

Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

Optimal Control of Drug Therapy in a Hepatitis B Model

Directory of Open Access Journals (Sweden)

Jonathan E. Forde

2016-08-01

Full Text Available Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

Science.gov (United States)

Wu, Eric Q; Birnbaum, Howard G; Zhang, Huabin F; Ivanova, Jasmina I; Yang, Elaine; Mallet, David

2007-09-01

2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on

Drug therapy for chronic idiopathic axonal polyneuropathy

NARCIS (Netherlands)

Vrancken, A. F. J. E.; van Schaik, I. N.; Hughes, R. A. C.; Notermans, N. C.

2004-01-01

BACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic

[Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

Science.gov (United States)

Gou, Q Y; Yu, R B; Shi, R H

2017-05-10

Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

Drug therapy for people with mental disorders in the view of nursing professionals

Directory of Open Access Journals (Sweden)

Camila Bonfim de Alcântara

2018-03-01

Full Text Available Abstract Objective: To identify the perception of nursing professionals about drug therapy for people with mental disorders. Methods: An exploratory qualitative research was carried out in four Psychosocial Care Centers of Curitiba, Paraná, Brazil. Data, collected from January to March 2015 using an individual semi-structured interview applied to 56 nursing professionals, were submitted to qualitative data analysis and interpretation as proposed by Creswell. Results: The data were organized into three thematic categories: drug therapy improves the life of the person with a mental disorder; negative and positive consequences related to drug therapy; and drug therapy as one of the resources needed to treat mental health. Conclusion: Nursing staff perceive the importance of medications as a resource to treat people with mental disorders as psychotropic drugs minimize he acute symptoms of disorders and improve living conditions when associated with other therapeutic resources.

[Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

Science.gov (United States)

Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

1991-01-01

On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands.

Science.gov (United States)

Branchi, Federica; Tomba, Carolina; Ferretti, Francesca; Norsa, Lorenzo; Roncoroni, Leda; Bardella, Maria Teresa; Conte, Dario; Elli, Luca

2016-01-01

Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs. © 2016 S. Karger AG, Basel.

Drug therapy problems identification by clinical pharmacists in a private hospital in Kuwait.

Science.gov (United States)

Bayoud, T; Waheedi, M; Lemay, J; Awad, A

2018-05-01

To report the types and frequency of drug therapy problems (DTPs) identified and the physician acceptance of the clinical pharmacist interventions in a private hospital in Kuwait. A retrospective cross-sectional study was conducted on 3500 patients admitted to the hospital between December 2010 and April 2013. A structured approach was used to identify DTPs and recommend interventions. Data were analyzed using MAXQDA version 11. A total of 670 DTPs were identified and recommendations were proposed to treating physicians for each DTP. Overdosage was the most frequently identified drug therapy problem (30.8%), followed by low dosage (17.6%), unnecessary drug therapy (17.3%), need for additional drug therapy (11.6%), and need for different drug product (11.6%). The drug classes most frequently involved were anti-infectives (36.9%), analgesics (25.2%), and gastrointestinal agents (15.5%). More than two-third of the interventions (67.5%) were accepted and implemented by physicians. The most frequently accepted interventions were related to nonadherence, adverse drug reaction, monitoring parameters, inappropriate dosage, and need for additional drug therapy. The current findings expand the existing body of data by reporting on pharmacist recommendations of identified DTPs and importantly, their high rate of acceptance and implementation by the treating physician. These results could serve as a springboard to support further development and implementation of clinical pharmacy services in other healthcare settings in Kuwait. Copyright © 2018 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Combining Immunotherapy with Standard Glioblastoma Therapy

Science.gov (United States)

This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.

THE INFLUENCE OF BIOFEEDBACK SESSIONS IN CLOSED LOOP OF HEART RATE VARIABILITY AND PACED BREATHING ON SYSTOLIC BLOOD PRESSURE CONTROL DURING STANDARD DRUG THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

S. A. S. Belal

2015-06-01

Full Text Available Changes of systolic blood pressure (SBP in biofeedback (BFB sessions with closed loop of paced breathing (PB and heart rate variability (HRV during standard drug therapy of arterial hypertension (AH was studied. 275 patients with 1-3 degree of AH (143 men and 132 women, mean age 58,55 ± 7,99 years was divided into two comparable groups: 1 - BFB (139 patients in investigated PB loop, 2 - control group (136 patients with BFB without PB. In both groups was performed 10 sessions of BFB. Changes of SBP depending on the stage and degree of AH, gender and age was assessed. BP was measured by the method of Korotkov’s with monometer Microlife BP AG1-20 in same conditions. Data were processed by parametric and nonparametric statistics. It is proved that the use of biofeedback in the loop of PB and HRV significantly (p < 0.01 exceeds in efficiency an isolated drug therapy in control of SBP at any stage and degree of AH in patients of both sexes in all age groups. Extent of the effect increases with the stage and degree of the disease and not related to the sex and age of the patient. Findings allow to recommend this technique in clinical practice.

Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

Directory of Open Access Journals (Sweden)

P Padma Rao

2015-01-01

Full Text Available Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with established parametric standards for manufacturing the drug. Materials and Methods: Pharmacognostic studies on leaves and young aerial parts of authentic samples of J. virginiana L. have been carried out; physico-chemical parameters of raw drug viz., extractive values, ash values, formulation, besides weight per mL, total solids, alcohol content along with High Performance Thin Layer Chromatography (HPTLC and ultraviolet visible studies have been worked out for mother tincture. Results: The leaves are needles, narrow and sharp at tips; stems are round with greyish white to brown bark possessing small lenticels and covered by imbricate leaves. Epidermal cells in the surface have polygonal linear sides with pitted walls containing crystals and starch. Stomata exclusively occur on the adaxial surface in linear rows. Hypodermis of leaf in T.S. is marked with 1-2 layered lignified sclerenchyma. 2-4 secretory canals are present with one conspicuously beneath midvein bundle. The young terminal axis is sheathed by two closely surrounding leaves while the mature stem possess four leaf bases attached. Vascular tissue of stem possesses predominant xylem surrounded by phloem containing sphaeraphides, prismatic crystals and starch grains. Uniseriate rays occur in the xylem. Mature stem possess shrivelled cork, followed by the cortex. Physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and

The Efficacy of Dog Assisted Therapy in Detained Drug Users: A Pilot Study in an Italian Attenuated Custody Institute.

Science.gov (United States)

Contalbrigo, Laura; De Santis, Marta; Toson, Marica; Montanaro, Maria; Farina, Luca; Costa, Aldo; Nava, Felice Alfonso

2017-06-24

Drug addiction is a major care and safety challenge in prison context. Nowadays, rehabilitation and specific therapeutic programs are suggested to improve health and well-being of inmates during their detention time and to reduce substance abuse relapse after release from prison. Among these programs, several studies reported the benefits for inmates coming from animal assisted interventions. In this pilot controlled study, we investigated the efficacy of a dog assisted therapy program addressed to 22 drug addicted male inmates housed in an attenuated custody institute in Italy. The study lasted six months, the treated group (12 inmates) was involved once a week for one hour in 20 dog assisted therapy sessions, whereas the control group (10 inmates) followed the standard rehabilitation program. One week before the beginning and one week after the end of the sessions, all inmates involved were submitted to symptom checklist-90-revised and Kennedy axis V. Inmates involved in the dog assisted therapy sessions significantly improved their social skills, reducing craving, anxiety and depression symptoms compared to the control group. Despite the limitation due to the small number of inmates enrolled and to the absence of follow up, we found these results encouraging to the use of dog assisted therapy as co-therapy in drug addicted inmates rehabilitation programs, and we claim the need of more extensive study on this subject.

Drug therapy for peripheral vestibular vertigo

Directory of Open Access Journals (Sweden)

L. M. Antonenko

2017-01-01

Full Text Available The choice of effective treatments for vestibular vertigo is one of the important problems, by taking into account the high prevalence of peripheral vestibular diseases. Different drugs, such as vestibular suppressants for the relief of acute vertigo attacks and vestibular compensation stimulants for rehabilitation treatment, are used to treat vestibular vertigo. Drug therapy in combination with vestibular exercises is effective in patients with vestibular neuronitis, Meniere's disease, so is that with therapeutic maneuvers in patients with benign paroxysmal positional vertigo. The high therapeutic efficacy and safety of betahistines permit their extensive use for the treatment of various vestibular disorders.

Nanomaterial-based drug delivery carriers for cancer therapy

CERN Document Server

Feng, Tao

2017-01-01

This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

Microsponges based novel drug delivery system for augmented arthritis therapy.

Science.gov (United States)

Osmani, Riyaz Ali M; Aloorkar, Nagesh H; Ingale, Dipti J; Kulkarni, Parthasarathi K; Hani, Umme; Bhosale, Rohit R; Jayachandra Dev, Dandasi

2015-10-01

The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug-polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug-polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.

The application of machine learning techniques in the clinical drug therapy.

Science.gov (United States)

Meng, Huan-Yu; Jin, Wan-Lin; Yan, Cheng-Kai; Yang, Huan

2018-05-25

The development of a novel drug is an extremely complicated process that includes the target identification, design and manufacture, and proper therapy of the novel drug, as well as drug dose selection, drug efficacy evaluation, and adverse drug reaction control. Due to the limited resources, high costs, long duration, and low hit-to-lead ratio in the development of pharmacogenetics and computer technology, machine learning techniques have assisted novel drug development and have gradually received more attention by researchers. According to current research, machine learning techniques are widely applied in the process of the discovery of new drugs and novel drug targets, the decision surrounding proper therapy and drug dose, and the prediction of drug efficacy and adverse drug reactions. In this article, we discussed the history, workflow, and advantages and disadvantages of machine learning techniques in the processes mentioned above. Although the advantages of machine learning techniques are fairly obvious, the application of machine learning techniques is currently limited. With further research, the application of machine techniques in drug development could be much more widespread and could potentially be one of the major methods used in drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

Science.gov (United States)

Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

Science.gov (United States)

Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

2009-02-01

Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

The comprehension of drug therapy in elderly in a family health unit

Directory of Open Access Journals (Sweden)

Maria Carolina Martinghi Spinola Moretti

2018-04-01

Full Text Available Introduction: The complex therapeutic regimen and aging changes contribute to the difficulty of understanding the drug therapy and treatment adherence. Objective: To evaluate the comprehension of drug therapy for elderly identifying the limiting factors to its adherence to the treatment. Methods: A descriptive, exploratory and quantitative study using na evaluation questionnaire of the comprehension of the drug therapy, mini-mental state examination and the Lawton scale in patients from the Adult Program of a Family Health Unit, in nearby São Paulo, SP, Brazil. Data were analyzed by χ2 tests or Fisher’s exact test, of Mann-Whitney or Kruskal-Wallis. Results: The sample consisted of 50 elderly patients with diabetes and/or arterial hypertension with the average age of 68.8 years and low education. Only 30% of them knew the name of the medications that they make use of, 6% understood the letter of the prescription, 24% thought there is no need to take their medications when they feel good; and 20% have abandoned treatment sometime. The factors that influenced the comprehension of the drug therapy were marital status, family composition, cognitive status, number of pills/day and level of education. Conclusion: The lack of understanding by the elderly about their drug therapy may hinder to its adherence to the treatment, lead to poor control of symptoms, and interfere directly in their health and quality of life.

Recent advances in targeted drug therapy for hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

FAN Yongqiang

2018-02-01

Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

Science.gov (United States)

Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

Standardization Study of Antifertility Drug - Pippalyadiyoga

Directory of Open Access Journals (Sweden)

D. Shaila

2005-01-01

Full Text Available The present paper deals with the standardization study of pippalyadiyoga powder. It is used as a long acting contraceptive. The standardization of compound drug has been achieved by physico-chemical analysis and high performance liquid chromatography (HPLC fingerprint studies. Quantitative evaluation of borax in pippalyadiyoga showed 19.08% as sodium borate. RP-HPLC was performed using methanol and water as mobile phase. The detection and quantification was performed at a wavelength of 345 nm. Linearity of detector response for piperine was between the concentrations 0.005% to 0.1%. The correlation coefficient obtained for the linearity was 0.998. The recovery value of standard piperine was 99.4%. Low value of standard deviation and coefficient of variation are indicative of high precision of the method. Quantitative evaluation of piperine in pippalyadiyoga was found to be 0.339%.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

Radiation therapy: model standards for determination of need

International Nuclear Information System (INIS)

Lagasse, L.G.; Devins, T.B.

1982-03-01

Contents: Health planning process; Health care requirements (model for projecting need for megavoltage radiation therapy); Operational objectives (manpower, megavoltage therapy and treatment planning equipment, support services, management and evaluation of patient care, organization and administration); Compliance with other standards imposed by law; Financial feasibility and capability; Reasonableness of expenditures and costs; Relative merit; Environmental impact

Novel Drug Delivery Technique for Breast Cancer Therapy

National Research Council Canada - National Science Library

Esenaliev, Rinat O

2004-01-01

.... We proposed to complete Task 3 and to implement Task 4 in the third year of the project. Task 3 focuses on in vivo studies of efficacy of cancer therapy with the use of ultrasound-enhanced delivery of anti-cancer drug 5-FU...

Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

International Nuclear Information System (INIS)

Alexiou, Christoph; Tietze, Rainer; Schreiber, Eveline; Jurgons, Roland; Richter, Heike; Trahms, Lutz; Rahn, Helene; Odenbach, Stefan; Lyer, Stefan

2011-01-01

The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: →Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. → Histology evidences the intravasation of particles enter the intracellular space. → Non-invasive imaging techniques can display the spatial arrangement of particles. → HPLC-analysis show outstanding drug enrichment in tumors after MDT.

Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

Energy Technology Data Exchange (ETDEWEB)

Alexiou, Christoph, E-mail: c.alexiou@web.d [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Tietze, Rainer; Schreiber, Eveline [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Jurgons, Roland [Franz Penzoldt Center, University Hospital Erlangen (Germany); Richter, Heike; Trahms, Lutz [PTB Berlin (Germany); Rahn, Helene; Odenbach, Stefan [TU Dresden, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Lyer, Stefan [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany)

2011-05-15

The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. Histology evidences the intravasation of particles enter the intracellular space. Non-invasive imaging techniques can display the spatial arrangement of particles. HPLC-analysis show outstanding drug enrichment in tumors after MDT.

Family Therapy for Drug Abuse: Review and Updates 2003-2010

Science.gov (United States)

Rowe, Cynthia L.

2012-01-01

Just 15 years ago, Liddle and Dakof ("Journal of Marital and Family Therapy," 1995; 21, 511) concluded, based on the available evidence, that family therapy represented a "promising, but not definitive" approach for the treatment of drug problems among adolescents and adults. Seven years later, Rowe and Liddle (2003) review described considerable…

Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

Science.gov (United States)

Yuan, Youyong; Liu, Bin

2014-09-10

A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

Microwave coagulation therapy and drug injection to treat splenic injury.

Science.gov (United States)

Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

2014-01-01

The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P microwave group than those in the 2450-MHz microwave and drug injection groups (P microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

Science.gov (United States)

Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

2017-06-01

Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential drug interactions in patients given antiretroviral therapy.

Science.gov (United States)

Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

2016-11-21

to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga

Standard dose 131I therapy for toxic multinodular goiter in an endemic goiter region

International Nuclear Information System (INIS)

Goncalves, E.; Castro, J.A.S.; Gross, J.L.

1986-01-01

The effect of the standard 15 mCi dose of 131 I on the thyroid function of 25 patients from an endemic goiter region with toxic multinodular goiter of different sizes was determined. The patients were followed for 1 to 5 years and 7 months (mean: 2 years and 10 months). Eighteen patients were treated with the antithyroid drugs propylthiouracil or methimazole before 131 I and seven only received 131 I. All but three patients achieved euthyroidism after a single dose of 131 I. Two patients in the antithyroid treatment group became hypothyroid 2 months and 2 years after the isotope therapy, respectively. Pretreatment with antithyroid drugs did not significantly modify the effectiveness of 131 I treatment. This simplified dose regimen of 131 I was effective in the treatment of hyperthyroidism caused by multinodular goiter in an endemic region, and the efficacy was independent of the size of the goiter. (author)

Competence of medical students in communicating drug therapy: Value of role-play demonstrations.

Science.gov (United States)

Tayem, Yasin I; Altabtabaei, Abdulaziz S; Mohamed, Mohamed W; Arrfedi, Mansour M; Aljawder, Hasan S; Aldebous, Fahad A; James, Henry; Al Khaja, Khalid A J; Sequeira, Reginald P

2016-01-01

This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students' competence in this skill. Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients.

Drug addiction therapy. A dance to the music of time.

Science.gov (United States)

Goodison, L; Schafer, H

1999-10-21

Dance therapy can play a useful role in the treatment and rehabilitation of women with drug addiction. It works by raising self-esteem through an improved relationship with the body, giving women the strength to help combat their habit. The benefits of dance therapy for women at the detox unit of Holloway Prison have been confirmed by prison staff.

Enhancing the Pediatric Drug Development Framework to Deliver Better Pediatric Therapies Tomorrow.

Science.gov (United States)

Bucci-Rechtweg, Christina

2017-10-01

Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development. These initiatives, in conjunction with a more sophisticated process of drug discovery and development, have led to significant advancements in the labeling of drugs for pediatric use. Facilitated by the emergence of new targets, precision medicine, and innovations in regulatory science, there is now a subtle shift in focus toward drug development research for children rather than simply in children. Although there has been an increase in pediatric studies of investigational agents and labeling of pediatric information for use, there have been unintended consequences of existing policies. As a result, limited progress has been made in certain therapeutic areas and for off-patent therapies. Future policy reform to enhance the availability and accessibility of pediatric medicines should not only reflect an understanding not only of the successes of existing policy and legislative initiatives but also constructively address failures and unintended consequences. Taken together, policy reform, global cooperation, and innovation in regulatory science will more ably deliver better pediatric therapies tomorrow. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A Randomized Controlled Trial of 7-Day Intensive and Standard Weekly Cognitive Therapy for PTSD and Emotion-Focused Supportive Therapy

Science.gov (United States)

Ehlers, Anke; Hackmann, Ann; Grey, Nick; Wild, Jennifer; Liness, Sheena; Albert, Idit; Deale, Alicia; Stott, Richard; Clark, David M.

2014-01-01

Objective Psychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice weekly over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals, (1) to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD, and (2) to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment. Method Patients with chronic PTSD (N=121) were randomly allocated to 7-day intensive or standard 3-month weekly cognitive therapy for PTSD, 3-month weekly emotion-focused supportive therapy, or a 14-week waitlist condition. Primary outcomes were PTSD symptoms and diagnosis as assessed by independent assessors and self-report. Secondary outcomes were disability, anxiety, depression, and quality of life. Measures were taken at initial assessment, 6 weeks and 14 weeks (post-treatment/wait). For groups receiving treatment, measures were also taken at 3 weeks, and follow-ups at 27 and 40 weeks after randomization. All analyses were intent-to-treat. Results At post-treatment/wait assessment, 73%, 77%, 43%, 7% of the intensive cognitive therapy, standard cognitive therapy, supportive therapy, and waitlist groups, respectively, had recovered from PTSD. All treatments were well tolerated and were superior to waitlist on all outcome measures, with the exception of no difference between supportive therapy and waitlist on quality of life. For primary outcomes, disability and general anxiety, intensive and standard cognitive therapy were superior to supportive therapy. Intensive cognitive therapy achieved faster symptom reduction and comparable overall outcomes to standard cognitive therapy. Conclusions Cognitive therapy for PTSD delivered intensively over little more than a week is as effective as cognitive therapy delivered

Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy

Science.gov (United States)

2014-05-01

from anti-cancer drug therapy [1,2]. Platinum drugs, taxanes, proteasome inhibitors, vinca alkaloids, epothilones, and immunomodulators are the...and immunomodulators are the standard of anti-cancer therapies for the six most cancers. An estimated 2010 incidence of 994, 680 cases for these

Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

Science.gov (United States)

Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

2010-05-01

The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy

Directory of Open Access Journals (Sweden)

Hao Chen

2017-08-01

Full Text Available Antibody-drug conjugates (ADCs are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation strategies, cytotoxic drugs, and their molecular targets has led to the successful development of several approved ADCs. These ADCs are powerful therapeutics for cancer treatment, enabling wider therapeutic windows, improved pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin inhibitors are one of the most successful cytotoxic drugs in the ADC armamentarium, this review focuses on the progress in tubulin inhibitor-based ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin inhibitors. This review should be helpful to facilitate future development of new generations of tubulin inhibitor-based ADCs for cancer therapy.

[Combination drug therapy in patients with BPH].

Science.gov (United States)

Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

2018-03-01

Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself

Treatment with antithyroid drugs or iodine following radioiodine therapy for Graves' disease

International Nuclear Information System (INIS)

Mazeto, Glaucia; Leal, B.M.B.; Souza, L.S.; Griva, B.L.; Moriguchi, S.M.; Moreira, C.C.; Lemos, A.C.; Kiy, Y.

2005-01-01

Full text: The effect of radioiodine ( 131 I) therapy in Graves' disease is gradual and the patients continue to be hyperthyroid for much time after this therapy. In a retrospective study, we compared the evolution of 196 patients in this situation treated with some therapeutic regimens. They received propylthiouracil or methimazole (ATD), one of them and potassium iodide (KI), KI only, or no drugs after 131 I therapy. ATD was started usually one day and KI two months after the radioiodine. The groups had similar age, pretreatment serum T 4 concentrations and 131 I treatment dose. Cure of the hyperthyroidism occurred in 83,9%, 75,5%, 75,0% and 70,6% in no-drugs, KI, ATD and KI-ATD groups, respectively. Hyperthyroidism was longer in KI and KI-ATD groups. Definitive hypothyroidism occurred in 39,2%, 47,2%, 52,9% and 66,1% in KI-ATD, KI, ATD and no-drugs groups, respectively. This condition appeared more quickly in no-drugs and ATD groups. Conclusion: We conclude that KI and ATD groups had similar evolutions as to cure of hyperthyroidism and occurrence of hypothyroidism. (author)

Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

OpenAIRE

Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

2002-01-01

Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

VNS Therapy versus the latest antiepileptic drug.

Science.gov (United States)

Ben-Menachem, Elinor; French, Jacqueline A

2005-09-01

Pro AED: The central issue in medical decision-making is risk-benefit assessment. Surgery of any type is still considered to be a major undertaking. To warrant these risks, the patient has a right to expect that they have a greater chance of a good outcome with an invasive therapy than with a non-invasive one. The main question is when, if ever, this becomes the case when comparing implantation of a VNS Therapy System versus adding an antiepileptic drug (AED)? After the first drug? The second? After all AEDs have failed? To date, no randomized trial comparing the addition of an AED against vagus nerve stimulation (VNS Therapy) has been undertaken, although several are currently being contemplated. Without this information, it is more difficult to make a case for early implementation of VNS Therapy. Unfortunately, few data are available regarding the potential for patients to become seizure-free after implantation of a VNS Therapy System. Another issue is side effects. It is important to remember that VNS Therapy also produces adverse events, albeit very different in character than those associated with AEDs, to which physicians have become accustomed. These include cough, dyspnea, pharyngitis, voice alteration and sleep apnea. A less frequently discussed, potentially negative consequence of VNS Therapy relates to the ability to obtain imaging of the patient. Patients who have undergone VNS Therapy System implantation are not candidates for imaging of the chest, breast, or abdomen. A second issue is that imaging of the brain can only be performed with MRI scanners that meet certain requirements, and as MRI technology develops, scanners meeting these requirements may become harder to find. However, to summarize, VNS Therapy is an excellent and useful treatment choice. Fortunately, the choice between AEDs and VNS Therapy is not an "either/or" decision. Each has a role in the treatment of patients with epilepsy, and the advantages and disadvantages of each should be

Synergistic gene and drug tumor therapy using a chimeric peptide.

Science.gov (United States)

Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2013-06-01

Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

International Nuclear Information System (INIS)

Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar; Singh, Satyawan

2013-01-01

Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

Directory of Open Access Journals (Sweden)

Swatantra Kumar Singh Kushwaha

2013-12-01

Full Text Available Carbon nanotubes (CNTs were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

Energy Technology Data Exchange (ETDEWEB)

Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar, E-mail: swatantrakushwaha@yahoo.co.in [Pranveer Singh Institute of Technology, Kanpur (India); Singh, Satyawan [Saroj Institute of Technology and Management, Lucknow (India)

2013-10-15

Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

Two drugs are better than one. A short history of combined therapy of ovarian cancer.

Science.gov (United States)

Bukowska, Barbara; Gajek, Arkadiusz; Marczak, Agnieszka

2015-01-01

Combined therapy of ovarian cancer has a long history. It has been applied for many years. The first drug which was commonly combined with other chemotherapeutics was cisplatin. It turned out to be effective given together with alkylating agents as well as with taxanes. Another drug which is often the basis of first-line therapy is doxorubicin. The use of traditional chemotherapy is often limited due to side effects. This is why new drugs, targeted specifically at cancer cells (e.g. monoclonal antibodies or epidermal growth factor receptor inhibitors), offer a welcome addition when used in combination with conventional anticancer agents. Drugs applied in combination should be synergistic or at least additive. To evaluate the type of interaction between drugs in a plausible sequence, isobolographic analysis is used. This method allows one to assess whether the two agents could make an efficient combination, which might improve the therapy of ovarian cancer.

Access to antiepileptic drug therapy in children in Camagüey Province, Cuba

Science.gov (United States)

Arencibia, Zeina Bárzaga; Leyva, Alberto López; Peña, Yordanka Mejías; Reyes, Alba Rosa González; Nápolez, Maurilys Acosta; Carbonell Perdomo, Demetrio; Manzano, Edita Fernández; Choonara, Imti

2012-01-01

Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries. PMID:23134098

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

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Alessandra Romano

2014-01-01

Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

Science.gov (United States)

Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

2014-01-01

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

Science.gov (United States)

Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar

2012-09-01

Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Individualization of anticancer therapy; molecular targets of novel drugs in oncology

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2012-11-01

Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

Science.gov (United States)

Zhan, Changyou; Li, Chong; Wei, Xiaoli; Lu, Wuyuan; Lu, Weiyue

2015-08-01

Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics. Some toxins have evolved from a relatively small number of structural frameworks that are particularly suitable for addressing the crucial issues of potency and stability, making them an instrumental source of leads and templates for targeted therapy. The focus of this review is on protein and peptide toxins for the development of targeted drug delivery systems and molecular therapies. We summarize disease- and biological barrier-related toxin receptors, as well as targeted drug delivery strategies inspired by those receptors. The design of new therapeutics based on protein and peptide toxins is also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

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BROSCATEAN, Emanuela-Flavia

2013-12-01

Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

Preclinical and clinical experience in vascular gene therapy: advantages over conservative/standard therapy.

Science.gov (United States)

Nikol, S; Huehns, T Y

2001-04-01

No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty or increase the formation of collaterals in ischemic tissue in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates or in inducing angiogenesis post-angioplasty and following stent implantation has encouraged the development of new technological treatment approaches. Gene therapy is a novel strategy with the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation, and to induce growth of new vessels or remodeling of pre-existing vessel branches, which may help patients with critical ischemia. Gene therapy strategies have the advantage of minimizing systemic side effects and may have a long-term effect as the encoded protein is released. Most clinical trials investigating gene therapy for vascular disease have been uncontrolled phase I and IIa trials. Gene therapy into vessels with the genes for growth factors has been demonstrated to be feasible and efficient. Local drug delivery devices have been used in combination with gene therapy in several trials to maximize safety and efficiency. Data from experimental animal work indicates that gene therapy may modify intimal hyperplasia after arterial injury, but there are few clinical trials on restenosis in patients. Preliminary clinical results show only limited success in altering restenosis rates. In vitro and experimental in vivo investigations into gene therapy for angiogenesis demonstrate increased formation of collaterals and functional improvement of limb ischemia. There is some evidence of increased collateral formation and clinical improvement in patients with critical limb ischemia. Results of placebo-controlled and double-blind trials of gene therapy for vascular disease are awaited.

Pharmokinetics in Drug Therapy as a Required Undergraduate Course

Science.gov (United States)

Schumacher, G. E.

1976-01-01

This course is offered in the third quarter of the fourth year of the five-year curriculum in pharmacology. The year includes (1) a 350-hour clinical clerkship, (2) two courses in "Case Studies in Drug Therapy," (3) one course in "Case Studies in Pharmacy Practice," and (4) professional electives. (LBH)

Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse:

DEFF Research Database (Denmark)

Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2015-01-01

trials. Meta-analytic methods were used to quantitatively synthesize study results.  Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions.  Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however......Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.  Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...

Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa.

Science.gov (United States)

Inzaule, Seth C; Ondoa, Pascale; Peter, Trevor; Mugyenyi, Peter N; Stevens, Wendy S; de Wit, Tobias F Rinke; Hamers, Raph L

2016-11-01

Increased provision of antiretroviral therapy in sub-Saharan Africa has led to a growing number of patients with therapy failure and acquired drug-resistant HIV, driving the demand for more costly further lines of antiretroviral therapy. In conjunction with accelerated access to viral load monitoring, feasible and affordable technologies to detect drug-resistant HIV could help maximise the durability and rational use of available drug regimens. Potential low-cost technologies include in-house Sanger and next-generation sequencing in centralised laboratories, and point mutation assays and genotype-free systems that predict response to antiretroviral therapy at point-of-care. Strengthening of centralised high-throughput laboratories, including efficient systems for sample referral and results delivery, will increase economies-of-scale while reducing costs. Access barriers can be mitigated by standardisation of in-house assays into commercial kits, use of polyvalent instruments, and adopting price-reducing strategies. A stepwise rollout approach should improve feasibility, prioritising WHO-recommended population-based surveillance and management of complex patient categories, such as patients failing protease inhibitor-based antiretroviral therapy. Implementation research, adaptations of existing WHO guidance, and political commitment, will be key to support the appropriate investments and policy changes. In this Personal View, we discuss the potential role of HIV drug resistance testing for population-based surveillance and individual patient management in sub-Saharan Africa. We review the strengths and challenges of promising low-cost technologies and how they can be implemented. Copyright © 2016 Elsevier Ltd. All rights reserved.

RNA Editing and Drug Discovery for Cancer Therapy

Directory of Open Access Journals (Sweden)

Wei-Hsuan Huang

2013-01-01

Full Text Available RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.

An Oral Contraceptive Drug Interaction Study

Science.gov (United States)

Bradstreet, Thomas E.; Panebianco, Deborah L.

2004-01-01

This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

[Deep brain stimulation in movement disorders: evidence and therapy standards].

Science.gov (United States)

Parpaley, Yaroslav; Skodda, Sabine

2017-07-01

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice. Georg Thieme Verlag KG Stuttgart · New York.

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

Science.gov (United States)

Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

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Vera M. Kroesen

2017-06-01

Full Text Available Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs, in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.

Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

Directory of Open Access Journals (Sweden)

Toril Andersen

2015-01-01

Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

Science.gov (United States)

Meyers, Todd

2014-06-01

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

[The relation of the patient's condition and outcome of drug maintainance therapy in schizophrenia (analysis of the curative effect in 324 cases)].

Science.gov (United States)

Zhang, Z

1989-12-01

Cf, the methodology and diagnostic standard of 12 collaborative units about "Epidemiological investigation" of 1982, we traced to investigate the relation between the patients' condition outcome and drug maintain therapy of 324 cases with schizophrenia in community. The investigative result showed the cure rate of insisting on taking medicine group was 25.21%, the effective rate was 97.48%, the cure rate of irregular taking medicine groups was 6.63%, the effective rate was 68.37%, there was remarkable difference between the cure rate and the effective rate in two groups. Otherwise we also compared the patients, condition of insisting on taking drug groups with during investigation. We found there was no remarkable change that showed insisting a drug maintain therapy out the hospital to the curative effect of the disease to possess on important meaning. The pattern also compared the curative effect of a time onset of disease group and many times. There was no remarkable difference about the statistical analysis of the curative effect among each group. It showed me never lose confidence to the patients. We should treat actively them.

The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case

Directory of Open Access Journals (Sweden)

N. V. Demidova

2016-01-01

Full Text Available Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab, and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA, a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

Drug Therapy.

Science.gov (United States)

He, Ri-Hui; Tao, Ran

2017-01-01

This chapter first summarizes the therapy of addiction disorder, and elaborates on the progress of medication. First, the difference between dependency and addiction are introduced. The basic principles of the therapy of substance and non-substance addiction are then put forward. It is also pointed out in this chapter that with the progress of the study, the goal of addiction disorder therapy is expected to transfer from reducing the relapse and harm of the addiction to completely eliminating and recovering from it. This chapter also introduces the progress of psychological addiction elimination technology, especially the "Unconditioned Stimulus Retrieval Extinction Paradigm and Conditioned Stimulus Retrieval Extinction Paradigm" and PITDH technology. Finally it is pointed out that in addiction disorder therapy, comprehensive intervention has become a trend. With regard to the medication for addiction disorders, this chapter also includes the progress and deficiencies of substance and non-substance addiction. In terms of addiction disorder rehabilitation, the foundation of substance addiction is medication which is, however, limited for non-substance addiction. The key to the rehabilitation of addiction disorder is psycho-behavioral therapy, which is especially effective in eliminating craving.

Principles governing heart failure therapy re-examined relative to standard evidence-based medicine-driven guidelines.

Science.gov (United States)

Tan, Lip-Bun; Chinnappa, Shanmugakumar; Tan, David K H; Hall, Alistair S

2011-09-01

Although all aspects of clinical work nowadays are modified by the pervading influence of evidence-based medicine (EBM) and multiplicative guidelines, not many clinicians realize that the underlying premise of EBM-driven guidelines is a particular strain of consequentialist ideology. Subservience to this ideology has transformed modern medical practice, but there is a real risk of distorting good medical practice, of belittling clinical judgement, of disempowering clinicians, and subjecting patients to skewed medical reality and treatment options. With so many heart failure (HF) guidelines issued by various august bodies, it is therefore timely to reappraise principles governing modern HF therapy with a fresh examination of the hierarchy of medical imperatives, the role of alternatives to consequentialism including deontological principles in HF therapy. In addition, other ideology worth re-examining, aside from EBM, are the principle of appropriate definition of HF underlying therapeutic goals and the principle of prioritizing objectives of HF therapy. Even within standard EBM, there are many questions to reconsider: about what types of evidence are admissible, different interpretations of available evidence, emphasizing patient-centered outcome measures instead of randomized controlled trials quantifiable therapeutic outcomes, how to prescribe drugs for prognostic versus symptomatic benefits, and how to deliver HF therapy based on pathophysiological features through mechanistic considerations and not just confined to randomized controlled trials or meta-analytical statistical imperatives. Through re-examination of these fundamental principles of HF therapy, it is hoped that clinicians will be empowered to manage HF patients more holistically and better deliver HF therapies in the best interest of each individual patient.

Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

Directory of Open Access Journals (Sweden)

Ponizovskiy MR

2015-04-01

Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

Behavioral couples therapy (BCT) for alcohol and drug use disorders: A meta-analysis

NARCIS (Netherlands)

Powers, M.B.; Vedel, E.; Emmelkamp, P.M.G.

2008-01-01

Narrative reviews conclude that behavioral couples therapy (BCT) produces better outcomes than individual-based treatment for alcoholism and drug abuse problems (e.g., [Epstein, E. E., & McCrady, B. S. (1998). Behavioral couples treatment of alcohol and drug use disorders: Current status and

Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

Directory of Open Access Journals (Sweden)

Jiming Chen

2008-03-01

Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles

Science.gov (United States)

Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

2014-09-01

The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

Directory of Open Access Journals (Sweden)

Warangkana Lohcharoenkal

2014-01-01

Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Protein nanoparticles as drug delivery carriers for cancer therapy.

Science.gov (United States)

Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie; Rojanasakul, Yon

2014-01-01

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

Science.gov (United States)

Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

2016-03-11

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

Directory of Open Access Journals (Sweden)

Giovana Maria Fioramonti Calixto

2016-03-01

Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

Science.gov (United States)

Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

Science.gov (United States)

Qiu, Meng; Wang, Dou; Liang, Weiyuan; Liu, Liping; Zhang, Yin; Chen, Xing; Sang, David Kipkemoi; Xing, Chenyang; Li, Zhongjun; Dong, Biqin; Xing, Feng; Fan, Dianyuan; Bao, Shiyun; Zhang, Han; Cao, Yihai

2018-01-16

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease

International Nuclear Information System (INIS)

Hayashi, Katsumi; Abe, Katsumi; Sakata, Ikuko; Sakaguchi, Chiharu; Yamamoto, Kentaro; Kosuda, Shigeru

2005-01-01

There is no comparative cost-utility study between 131 I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131 I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131 I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131 I therapy. A simulation of 1,000 female patients weighing≥50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131 I therapy strategy. These results quantitatively demonstrated that the 131 I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131 I therapy should be used more widely in Japan because of its greater utility and lower cost. (author)

A preliminary study of spiritual self-schema (3-S(+)) therapy for reducing impulsivity in HIV-positive drug users.

Science.gov (United States)

Margolin, Arthur; Schuman-Olivier, Zev; Beitel, Mark; Arnold, Ruth M; Fulwiler, Carl E; Avants, S Kelly

2007-10-01

The purpose of this study was twofold. First, pretreatment correlations are presented among impulsivity, intoxicant use, HIV risk behavior, spirituality, and motivation in a sample of 38 HIV-positive drug users. Second, treatment outcomes are presented from a preliminary study of spiritual self-schema (3-S(+)) therapy - a manual-guided psychotherapy integrating cognitive and Buddhist psychologies - for increasing motivation for abstinence, HIV prevention, and medication adherence. Impulsivity was negatively correlated with spiritual practices and motivation for recovery, and was positively related to intoxicant use and HIV risk behavior. Relative to a standard care comparison condition, patients completing 3-S(+) therapy reported greater decreases in impulsivity and intoxicant use, and greater increases in spiritual practices and motivation for abstinence, HIV prevention, and medication adherence. (c) 2007 Wiley Periodicals, Inc.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Science.gov (United States)

Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.

Effects of aerobic exercise and drug therapy on blood pressure and ...

African Journals Online (AJOL)

EB

Key words: Aerobic exercise, drug therapy, blood pressure, randomised controlled trial. African Health Sciences 2013; (1): .... body fat and displayed it on the screen of the meter. ... inelastible tape measure (Butterfly, China). Blood pressure ...

Aspirin plus dipyridamole has the highest surface under the cumulative ranking curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse event rate among 7 drug therapies in the treatment of cerebral infarction.

Science.gov (United States)

Zhang, Jian-Jun; Liu, Xin

2018-03-01

The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%). Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

Standard and Nonstandard Craniospinal Radiotherapy Using Helical TomoTherapy

International Nuclear Information System (INIS)

Parker, William; Brodeur, Marylene; Roberge, David; Freeman, Carolyn

2010-01-01

Purpose: To show the advantages of planning and delivering craniospinal radiotherapy with helical TomoTherapy (TomoTherapy Inc., Madison, WI) by presenting 4 cases treated at our institution. Methods and Materials: We first present a standard case of craniospinal irradiation in a patient with recurrent myxopapillary ependymoma (MPE) and follow this with 2 cases requiring differential dosing to multiple target volumes. One of these, a patient with recurrent medulloblastoma, required a lower dose to be delivered to the posterior fossa because the patient had been previously irradiated to the full dose, and the other required concurrent boosts to leptomeningeal metastases as part of his treatment for newly diagnosed MPE. The final case presented is a patient with pronounced scoliosis who required spinal irradiation for recurrent MPE. Results: The four cases presented were planned and treated successfully with Helical Tomotherapy. Conclusions: Helical TomoTherapy delivers continuous arc-based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Increased healthy tissue sparing is achieved at higher doses albeit at the expense of larger volumes of tissue receiving lower doses. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very elegant dose distributions. Daily megavoltage computed tomography imaging allows for precision of patient positioning, permitting a reduction in planning margins and increased healthy tissue sparing in comparison with standard techniques.

Assessment of patients' knowledge of their drug therapy in a ...

African Journals Online (AJOL)

Patients' knowledge of their medications is an important factor in ensuring adherence. Medication adherence is essential for rational drug use and derivation of optimal therapy. This study was conducted to assess knowledge of outpatients regarding their medications. A well structured questionnaire was administered to 200 ...

Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday.

Science.gov (United States)

Villa, Jordan C; Gianakos, Arianna; Lane, Joseph M

2016-02-01

Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer-review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options.

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

Science.gov (United States)

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Cognitive-Behavioral Therapies for Young People in Outpatient Treatment for Nonopioid Drug Use

Science.gov (United States)

Filges, Trine; Jorgensen, Anne-Marie Klint

2018-01-01

Objectives: This review evaluates the evidence on the effects of cognitive-behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for Non-Opioid Drug Use:

DEFF Research Database (Denmark)

Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken

2015-01-01

), Multidimensional Family Therapy (MDFT), and Psychoeducational Therapy (PET)). RESULTS Our main objective was to evaluate the current evidence on the effect of CBT on abstinence and drug use reduction for young people in outpatient treatment for non-opioid drug use. Seven randomised trials, involving 953......, and PET ) with respect to reduction in young people’s drug use. The evidence drawn from this systematic review is based on seven included studies analysed in two separate analyses, depending on whether the intervention was CBT with an add-on component such as motivational interviewing (four studies......) or CBT without an add-on component (three studies). The seven studies are very different in terms of their findings regarding the effects of CBT interventions compared to other interventions (ACRA, CBOP (+ACC), DHPE, FFT, IT, MDFT, and PET ) on young people’s drug use. Therefore, the overall conclusion...

Dual antiretroviral therapy for HIV infection.

Science.gov (United States)

Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

2017-08-01

For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

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Subramanian Palani

2016-01-01

Full Text Available Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of authentic raw drug have been carried out; physicochemical parameters, namely, extractive value, ash values, formulation besides weight per mL, total solids, alcohol content along with high-performance thin layer chromatography (HPTLC and ultraviolet studies for mother tincture have been worked out. Results: Roots are blackish-brown, wiry, rounded with irregular striations, tortuous; internally, it is softwood, light-yellow, and fracture fibrous. Phellem is 8-10 layered, discontinuous, and tanniniferous. Phellogen is two-layered and contains inulin crystals in few. Outer phelloderm is 12-16 layered often containing spherocrystals and associated with stone cells. Secondary phloem is up to 25 layered. Xylem is in the form of strips. The physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and organoleptic characters along with anatomical and physicochemical studies are diagnostic to establish standards for the drug.

STANDARDIZATION OF CUPPING THERAPY POINTS AND MECHANISM OF ACTION IN THE LIGHT OF SCIENCE

OpenAIRE

Dr. Izharul Hasan

2018-01-01

Now a day’s cupping therapy is an established therapeutic modality among Indian system of medicine as well as worldwide. Inspite of that, standard operative procedure (SOPs) for cupping therapy is yet to develop. In this paper author comprises the possible indications of cupping therapy along with procedures, application points, safety concerns, historical perspective, surgical operative standards described in traditional system of medicine as well as in the light of science. Cupping may be d...

42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

Science.gov (United States)

2010-10-01

... PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.153 Drug utilization... 42 Public Health 3 2010-10-01 2010-10-01 false Drug utilization management, quality assurance, and medication therapy management programs (MTMPs). 423.153 Section 423.153 Public Health CENTERS FOR MEDICARE...

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

International Nuclear Information System (INIS)

Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

2009-01-01

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Standard on microbiological management of fluids for hemodialysis and related therapies by the Japanese Society for Dialysis Therapy 2008.

Science.gov (United States)

Kawanishi, Hideki; Akiba, Takashi; Masakane, Ikuto; Tomo, Tadashi; Mineshima, Michio; Kawasaki, Tadayuki; Hirakata, Hideki; Akizawa, Tadao

2009-04-01

The Committee of Scientific Academy of the Japanese Society for Dialysis Therapy (JSDT) proposes a new standard on microbiological management of fluids for hemodialysis and related therapies. This standard is within the scope of the International Organization for Standardization (ISO), which is currently under revision. This standard is to be applied to the central dialysis fluid delivery systems (CDDS), which are widely used in Japan. In this standard, microbiological qualities for dialysis water and dialysis fluids are clearly defined by endotoxin level and bacterial count. The qualities of dialysis fluids were classified into three levels: standard, ultrapure, and online prepared substitution fluid. In addition, the therapeutic application of each dialysis fluid is clarified. Since high-performance dialyzers are frequently used in Japan, the standard recommends that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis facilities. It also recommends that the dialysis equipment safety management committee at each facility should validate the microbiological qualities of online prepared substitution fluid.

Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy.

Science.gov (United States)

Palmer, Adam C; Sorger, Peter K

2017-12-14

Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

Science.gov (United States)

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

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George L Drusano

Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

Radioiodine therapy and thyrostatic drugs and iodine

Energy Technology Data Exchange (ETDEWEB)

Moka, D.; Dietlein, M.; Schicha, H. [Department of Nuclear Medicine, University of Cologne, Joseph Stelzmannstrasse 9, 50924 Koeln (Germany)

2002-08-01

Radioiodine therapy is now the most common definite treatment for persistent hyperthyroidism. The outcome of radioiodine therapy depends mainly on the absorbed energy dose in the diseased thyroid tissue. The administered activity and the resulting target dose in the thyroid depend on both the biokinetics of radioiodine and the actual therapeutic effect of radioiodine in the thyroid. Thyrostatic drugs have a major influence on the kinetics of radioiodine in the thyroid and may additionally have a radioprotective effect. Pre-treatment with thyrostatic medication lowers the effective half-life and uptake of radioiodine. This can reduce the target dose in the thyroid and have a negative influence on the outcome of the therapy. Discontinuation of medication shortly before radioiodine administration can increase the absorbed energy dose in the thyroid without increasing the whole-body exposure to radiation as much as would a higher or second radioiodine administration. Furthermore, administration of non-radioactive iodine-127 2-3 days after radioiodine administration can also increase the effective half-life of radioiodine in the thyroid. Thus, improving the biokinetics of radioiodine will allow lower activities to be administered with lower effective doses to the rest of the body, while achieving an equally effective target dose in the thyroid. (orig.)

Management of noninfectious posterior uveitis with intravitreal drug therapy

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Tan HY

2016-10-01

Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

Fighting cancer with nanomedicine---drug-polyester nanoconjugates for targeted cancer therapy

Science.gov (United States)

Yin, Qian

The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.

Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for NonOpioid Drug Use

DEFF Research Database (Denmark)

Filges, Trine; Jørgensen, Anne-Marie Klint

2016-01-01

Objectives: This review evaluates the evidence on the effects of cognitive–behavioral therapy (CBT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials...

Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use

DEFF Research Database (Denmark)

Filges, Trine; Andersen, Ditte

2016-01-01

Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized...... and nonrandomized trials. Results: The search yielded two studies that met inclusion criteria. Only one study provided numerical results on the effect of FFT on drug use reduction. Conclusions: There is insufficient evidence to allow any conclusion to be drawn on the effect of FFT for young people in treatment...

Brief strategic family therapy for young people in treatment for drug use

DEFF Research Database (Denmark)

Lindstrøm, Maia; Filges, Trine; Jørgensen, Anne-Marie Klint

2015-01-01

This review evaluates the evidence on the effects of brief strategic family therapy (BSFT) on drug use reduction for young people in treatment for nonopioid drug use. Method: We followed Campbell Collaboration guidelines to prepare this review and ultimately located three studies for final analysis...... and interpretation. Results: The results are mixed: BSFT does not seem to have better or worse effects on drug use frequency and family functioning than other treatments but has positive effects on treatment retention compared to control conditions. Longer retention in treatment has been identified as a consistent...

帕金森病的药物治疗%Drug therapy for Parkinson's disease

Institute of Scientific and Technical Information of China (English)

杨任民

2011-01-01

帕金森病(PD)的多种治疗药物是针对运动症状的治疗,而PD非运动症状可降低患者生活质量,甚至可加重PD患者的运动症状和功能残疾,其治疗也不容忽视.本文综述PD运动症状的药物治疗原则,以及各类药物的临床使用及其疗效评价,同时汇总多种非运动症状的药物治疗研究.%Several drugs have been used to treat the motor symptoms of Parkinson's disease (PD). Non-motor symptoms may reduce quality of life, cause more motor symptoms and functional disability in PD patients. The therapy for non-motor symptoms should not be ignored. This review describes the principle and application of drug therapy for motor symptoms of PD, and summarizes drug therapy for a variety of non-motor symptoms.

Characteristics of Hemorrhagic Peptic Ulcers in Patients Receiving Antithrombotic/Nonsteroidal Antiinflammatory Drug Therapy

OpenAIRE

Nakamura, Kazuhiko; Akahoshi, Kazuya; Ochiai, Toshiaki; Komori, Keishi; Haraguchi, Kazuhiro; Tanaka, Munehiro; Nakamura, Norimoto; Tanaka, Yoshimasa; Kakigao, Kana; Ogino, Haruei; Ihara, Eikichi; Akiho, Hirotada; Motomura, Yasuaki; Kabemura, Teppei; Harada, Naohiko

2012-01-01

Background/Aims Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were c...

Chinese herbal therapy and Western drug use, belief and adherence for hypertension management in the rural areas of Heilongjiang province, China.

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Xia Li

Full Text Available Traditional Chinese medicine (TCM including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users. When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.

Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

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Anish Babu

2013-01-01

Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

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Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

Treatment of hyperthyroidism with radioiodine: adjunctive therapy with antithyroid drugs reconsidered

International Nuclear Information System (INIS)

Velkeniers, B.; Vanhaelst, L.; Cytryn, R.; Jonckheer, M.H.

1988-01-01

To assess the value of antithyroid drugs as an adjunct to radioactive iodine for the treatment of hyperthyroidism the incidence of relapse or hypothyroidism after a mean follow-up of 51/2 years (range 2-7 years) was reviewed retrospectively for 206 patients, some treated with and others without antithyroid drugs after radioiodine therapy. Allocation to treatment group had been random, and both groups were similar in all respects except for the adjunctive treatment with antithyroid drugs. All doses of 131 I had been calculated by one physician. Compared with those who received 131 I alone, those starting on antithyroid drugs within 8 days after 131 I had a lower incidence of hypothyroidism but a higher incidence of early post-treatment recurrence or persistence of hyperthyroidism, and considerably lower incidence of remission. (author)

Study and comparison of the meta cognitive-emotional processing and drug therapy in modifying emotional, cognitive and social skills in bipolar disorders

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fatemeh bahrami

2009-11-01

Full Text Available Psychotherapy for bipolor disorder has been very much neglected. The aim of this study was to determine and compare the meta cognitive, emotional processing training (MEPT with medical and standard therapy (drug in increasing emotional, cognitive and social skills, of the patients with bipolar disorders. Materials and Methods: This semi experimental study with control group was carried out on 32 females in the 16-40 age bracket, diagnosed with bipolar disorder by means of DSM - IV –R criteria selected among referrals from Isfahan hospitals and psychology clinics. One group randomly received medical therapy plus MEPT. The second group (control group received standard drug therapy. Data gathering instruments were a semi – structural interview based on DSM – IV – R criteria and the following questionnaires: Mania (Bech, et al, 1979, Depression (Hamilton, 1980, Emotional intelligence (Cooper, 1999, Self – control (Rosenbaum, 1980, Insigt (David, et al, 1992, Social function (Hurry, et al, 1983. And the Aconomic, social, cultural questionnaire was used to control social ststus of the subjects. this questionnaire was made by the researcher. Results: The MEPT method influenced on increasing all of the emotional skills, sub scales and total scales. And also influenced on cognitive scales such as: dysfunctional thought, (p=0. 000, insight (p=0. 05, self – control (p=0. 000. Social skills could be increased (p=0. 02 by use of MEPT. Conclusion: Using pschological treatment in addition to pharmacotherapy increases treatment efficay. Therefor an educational program about MEPT is necessary for therapists.

A strategy to develop and implement Canadian standards for quality assurance in radiation therapy

International Nuclear Information System (INIS)

1999-05-01

In Canada, the Atomic Energy Control Board (AECB) regulates the limits of radiation exposure to the public and to workers in industry. In 1993, it discussed the fact that the safety of radiation therapy patients who receive medical exposures is not regulated [AE93]. The Group of Medical Advisors (GMA) to the AECB initiated a research contract to review quality assurance in Canadian radiation oncology centres and nuclear medicine departments. The review [MA95] revealed that the level of quality assurance in radiation therapy facilities varied across the country. As a result, the GMA undertook its own review of quality assurance in radiation therapy centres and made recommendations on how to achieve a uniform national system [MA98]. In response to the GMA report, the President of the AECB formed a Joint Working Group (JWG-11) to propose how Canadian Standards for Quality Assurance in Radiation Therapy could be developed and implemented. These national standards for quality assurance will serve as a common basis for establishing and evaluating quality assurance programs at individual radiation therapy centres. These standards should address the structure of quality assurance programs and quality assurance for radiation therapy equipment, personnel, and procedures. (author)

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

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Tai-Chi Lin

2015-11-01

Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

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Justin Cohen

2017-08-01

Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?

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Anna Gumieniczek

2016-05-01

Full Text Available Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs’ action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs – analogs of glucagon-like peptide 1 (GLP-1, inhibitors of dipeptidyl peptidase IV (DPPIV and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2 – has been made, based on a review of the literature over the past five years (2010-2014. The information included in the present review concerns the structure and activity relationship, therapeutic efficacy, side effects and the observed additional therapeutic effects, which can determine new standards in therapy of diabetes and also facilitate the development of better antidiabetic drugs.

Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

Science.gov (United States)

Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

2017-06-23

The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

Study and comparison of the meta cognitive-emotional processing and drug therapy in modifying emotional, cognitive and social skills in bipolar disorders

OpenAIRE

fatemeh bahrami; seyed kamal Solati dehkordi; ali farhadi

2009-01-01

Psychotherapy for bipolor disorder has been very much neglected. The aim of this study was to determine and compare the meta cognitive, emotional processing training (MEPT) with medical and standard therapy (drug) in increasing emotional, cognitive and social skills, of the patients with bipolar disorders. Materials and Methods: This semi experimental study with control group was carried out on 32 females in the 16-40 age bracket, diagnosed with bipolar disorder by means of DSM - IV –R crite...

Role of antithyroid drug treatment prior to radioiodine therapy in hyperthyroidism

International Nuclear Information System (INIS)

Das, B.K.; Pradhan, P.K.; Senthilnathan, M.S.; Malhotra, G.

2005-01-01

Full text: Radio Iodine (RI) therapy is preceded by anti thyroid drug treatment in most centres. There is a general notion that this is a pre-requisite for RI therapy. There have been some sporadic reports in the past emphasizing that euthyroid state is not necessary in all cases before RI. However, no prospective randomized study has been reported in recent literature. The aim of this prospective study was to find out whether prior treatment with anti thyroid drugs showed any advantage in comparison to direct application of radio iodine in hyperthyroid patients. Seventy-two clinically and bio chemically proven cases of hyperthyroidism were randomized into two groups , each with 36 patients. They were matched by age, sex and size of goiter. After establishment of the diagnosis the patients were either subjected to anti thyroid drug treatment (Group A) or given calculated dose of radio iodine (Group B). After being euthyroid for at least 4 weeks the Group A patients were asked to stop the drugs (Neomercazole) for 3-5 days and radio iodine was administered. Patients in both groups were prescribed beta blockers for 4-6 weeks. Average radio iodine dose in both groups was 5 ± 0.92 mCi. All patients were evaluated both clinically and bio chemically 3, 6, 12 months after the radio iodine application. The duration to achieve euthyroid state, patient tolerance and side effects if any were meticulously recorded. In the pre treated group 72.1, 83.4 and 97.2% of the patients attained euthyroid state at 3, 6, 12 months respectively. Five patients needed a second dose after 3 months. No side effect or complications were observed. In group B 77.7, 88.8 and 94.4% of patients achieved euthyroid status at 3, 6 and 12 months respectively. There was no side effects or complications noted. However, 16.7 and 22.2% of the patients in group A and 27.7 and 36.1% of the group B became hypothyroid at 6 and 12 months respectively. They were treated with Thyroxine supplementation. Overall

High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.

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Justen Manasa

Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

Impact of use of alcohol and illicit drugs by AIDS patients on adherence to antiretroviral therapy in Bahia, Brazil.

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Teixeira, Celia; Dourado, Maria De Lourdes; Santos, Marcio P; Brites, Carlos

2013-05-01

Use of alcohol and illicit drugs is a common finding among HIV-infected individuals, but there are many open questions about its impact on adherence to antiretroviral therapy and virological outcomes. Our study aimed to evaluate the impact of the use of alcohol and illicit drugs on the adherence to antiretroviral therapy (ART) among patients starting ART in Salvador, Brazil. We followed up 144 AIDS patients initiating ART for a 6-month period. At baseline, they were interviewed about demographics, behavior, and use of illicit drugs and alcohol. All of them had HIV-1 RNA plasma viral load and CD4(+)/CD8(+) cells count measured before starting therapy. After 60 days of treatment they were asked to answer a new questionnaire on adherence to ART. All patients were monitored during the following months, and new CD4(+) cell count/HIV-1 RNA plasma viral load determinations were performed after 6 months of therapy. Optimal adherence to therapy was defined by self-reported questionnaire, by 95% use of prescribed drug doses, and by using plasma HIV-1 RNA viral load as a biological marker. A total of 61 (42.4%) patients reported alcohol use, 7 (4.9%) used illicit drugs, and 17 (11.8%) used both alcohol and illicit drugs. Being in a steady relationship was protective to nonadherence (95% CI: 0.18-0.84). Missing more than two medical visits was also associated with a 68% higher likelihood of nonadherence (95% CI: 0.10-1.02). After logistic regression we detected a higher risk of nonadherence for patients declaring use of alcohol plus illicit drugs (odds ratio=6.0; 95% CI: 1.78-20.28) or high-intensity use of alcohol (odds ratio=3.29; 95% CI: 1.83-5.92). AIDS patients using alcohol and/or illicit drugs are socially vulnerable, and need specific and flexible programs, combining mental health care, harm reduction strategies, and assisted drug therapy to maximize the chances of successful use of ART.

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

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Juan D Unciti-Broceta

2015-06-01

Full Text Available African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

[Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

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Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

2014-03-04

Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

G2 checkpoint abrogator abates the antagonistic interaction between antimicrotubule drugs and radiation therapy

International Nuclear Information System (INIS)

Sui Meihua; Zhang Hongfang; Di Xiaoyun; Chang Jinjia; Shen Youqing; Fan Weimin

2012-01-01

Background and purpose: We previously demonstrated that radiation may arrest tumor cells at G2 phase, which in turn prevents the cytotoxicity of antimicrotubule drugs and results in antagonistic interaction between these two modalities. Herein we tested whether G2 abrogators would attenuate the above antagonistic interaction and improve the therapeutic efficacy of combination therapy between radiation and antimicrotubule drugs. Materials and methods: Breast cancer BCap37 and epidermoid carcinoma KB cell lines were administered with radiation, UCN-01 (a model drug of G2 abrogator), paclitaxel or vincristine, alone or in combinations. The antitumor activities of single and combined treatments were analyzed by a series of cytotoxic, apoptotic, cell cycle, morphological and biochemical assays. Results: UCN-01 significantly enhanced the cytotoxicity of radiation, antimitotic drugs, and their combined treatments in vitro. Further investigations demonstrated that UCN-01 attenuated radiation-induced G2 arrest, and subsequently repressed the inhibitory effect of radiation on drug-induced mitotic arrest and apoptosis. Conclusions: This is the first report demonstrating that G2 checkpoint abrogation represses the inhibitory effect of radiation on antimicrotubule drugs, which may be implicated in cancer combination therapy. Considering that G2 abrogators are under extensive evaluation for cancer treatment, our findings provide valuable information for this class of promising compounds.

IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

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Fu X

2017-05-01

Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

APPLICABILITY OF THE NON STEROID ANTIINFLAMMATORY DRUGS IN FEVER THERAPY OF CHILDREN

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O.A. Mubarakshina

2008-01-01

Full Text Available The non steroid anti-inflammatory drugs are widely applied in the pediatric practices for the fever therapy among children. While choosing the medications from this group to prescribe them to the children, it is essential to get guided towards the highly efficient medications with the least risk of the side effects. Only Paracetamol and ibuprofen are fully compliant with this requirement. They are officially recommended by who as the anti febrile medications for use in pediatrics. In the given article, the author reviews the advantages of ibuprofen over to Paracetamol based on the data from the foreign randomized research. She pays certain attention to the safety issues during the ibuprofen based treatment and to the opportunities of the combined Paracetamol and ibuprofen based therapy.Key words: fever, treatment, non steroid anti-inflammatory drugs, children.

Pulmonary fibrosis associated with psychotropic drug therapy: a case report

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Thornton Clare

2009-11-01

Full Text Available Abstract Introduction Sertraline and Risperidone are commonly used psychotropic drugs. Sertraline has previously been associated with eosinopilic pneumonia. Neither drug is recognised as a cause of diffuse fibrotic lung disease. Our report represents the first such case. Case Presentation We describe the case of a 33 year old Asian male with chronic schizophrenia who had been treated for three years with sertraline and risperidone. He presented to hospital in respiratory failure following a six month history of progressive breathlessness. High resolution CT scan demonstrated diffuse pulmonary fibrosis admixed with patchy areas of consolidation. Because the aetiology of this man's diffuse parenchymal lung disease remained unclear a surgical lung biopsy was undertaken. Histological assessment disclosed widespread fibrosis with marked eosinophillic infiltration and associated organising pneumonia - features all highly suggestive of drug induced lung disease. Following withdrawal of both sertraline and risperidone and initiation of corticosteroid therapy the patient's respiratory failure resolved and three years later he remains well albeit limited by breathlessness on heavy exertion. Conclusion Drug induced lung disease can be rapidly progressive and if drug exposure continues may result in respiratory failure and death. Prompt recognition is critical as drug withdrawal may result in marked resolution of disease. This case highlights sertraline and risperidone as drugs that may, in susceptible individuals, cause diffuse pulmonary fibrosis.

Drug utilization and therapy provision patterns by prescriber types among patients with systemic lupus erythematosus in Korea

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Shin S

2017-10-01

Full Text Available Sooyoung Shin College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST, Ajou University, Yeongtong-gu, Suwon, Republic of Korea Background: Systemic lupus erythematosus (SLE poses a growing challenge for healthcare systems, affecting an increasing number of people in Korea. This study aimed to investigate the prescribing patterns of SLE therapies and to compare common drug regimens prescribed by provider types.Methods: Sampled national health insurance claims data in 2015 were used to select eligible SLE patients. Frequency analyses were carried out regarding patient characteristics related to relevant SLE prescriptions. Patient-days were calculated per substance and per drug class and then categorized by provider types. Differences in drug utilization trends among the main types of providers were examined with the chi-square test.Results: A total of 2,074 patients with SLE were selected for study inclusion. Systemic corticosteroid therapy was provided for up to 67.9% of patients, frequently in conjunction with other SLE therapies. About 33.2% and 18.7% of steroid users were treated for more than 150 days and 300 days during the study period, respectively. The provider group that most frequently prescribed systemic corticosteroids was dermatologists. Hydroxychloroquine, an antimalarial considered pivotal to SLE management, was prescribed for only 32.4% of patients, predominantly by rheumatologists. Antimalarial therapy was associated with the longest therapy duration (257.7±120.1 days, followed by immunosuppressant therapy (187.0±153.0 days. Prescription rates of antimalarials and immunosuppressants were substantially lower in primary care doctor group and particularly in dermatologist group, compared to rheumatologist group (P-value associated with prescription patterns by provider types was <0.001 for both drug classes.Conclusion: The drug utilization patterns among the main provider groups commonly

Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

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Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

2010-07-01

The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy.

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Pasipanodya, Jotam G; Srivastava, Shashikant; Gumbo, Tawanda

2012-07-01

Using hollow-fiber tuberculosis studies, we recently demonstrated that nonadherence is not a significant factor for ADR and that therapy failure only occurs after a large proportion of doses are missed. Computer-aided clinical trial simulations have suggested that isoniazid and rifampin pharmacokinetic variability best explained poor outcomes. We were interested in determining whether isoniazid pharmacokinetic variability was associated with either microbiological failure or ADR in the clinic. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Prospective, randomized, controlled clinical trials that reported isoniazid acetylation status and microbiological outcomes were selected. The main effects examined were microbiological sputum conversion, ADR, and relapse. Effect size was expressed as pooled risk ratios (RRs) comparing rapid with slow acetylators. Thirteen randomized studies with 1631 rapid acetylators and 1751 slow acetylators met inclusion and exclusion criteria. Rapid acetylators were more likely than slow acetylators to have microbiological failure (RR, 2.0; 95% confidence interval [CI], 1.5-2.7), ADR (RR, 2.0; CI, 1.1-3.4), and relapse (RR, 1.3; CI, .9-2.0). Higher failure rates were encountered even in drug regimens comprising >3 antibiotics. No publication bias or small-study effects were observed for the outcomes evaluated. Pharmacokinetic variability to a single drug in the regimen is significantly associated with failure of therapy and ADR in patients. This suggests that individualized dosing for tuberculosis may be more effective than standardized dosing, which is prescribed in directly observed therapy programs.

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

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Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A drug's life: the pathway to drug approval.

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Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Should pediatric patients with hyperlipidemia receive drug therapy?

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Bhatnagar, Deepak

2002-01-01

Hyperlipidemia is now established as a major risk factor for causation of coronary heart disease (CHD) in adults; however, there is much debate on the level of coronary risk at which lipid-lowering drugs should be used. These issues of possible harm or lack of benefit from long-term use of lipid-lowering therapy, and cost effectiveness, are also pertinent in the pediatric setting. Evidence from several countries indicates that children have an increasing prevalence of obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high serum lipids 'track' these increased levels into adulthood. In some countries there is a trend to screen children for hypercholesterolemia. Family history itself is a poor discriminator in determining which children need to be screened and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can improve prediction. Measuring high density lipoprotein cholesterol also helps, but obesity appears to be the best marker for screening children at high risk. These considerations should not cloud the need for case finding and treatment of children with genetic disorders. Low fat diets have been shown to be well tolerated and effective in children; however, there are no major long-term studies demonstrating harm or benefit in those on lipid-lowering drugs. Nevertheless, concerns regarding the psychological effect and the theoretical metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should be generally restricted to children with genetic disorders of lipid metabolism. Children with diabetes mellitus, hypertension or nonlipid-related inherited disorders leading to premature CHD in adults should be treated with diet, and with lipid-lowering drugs when they reach adulthood. Children with secondary hyperlipidemia should be assessed individually. A number of drugs and nutriceuticals are available for use in children, but only a few drugs are licensed for use in children.

Interventional procedures and future drug therapy for hypertension

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Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

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Emmerton, Lynne; Rizk, Mariam F S; Bedford, Graham; Lalor, Daniel

2015-02-01

Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports. © 2014 John Wiley & Sons, Ltd.

Indefinite antithyroid drug therapy in toxic Graves′ disease: What are the cons

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Rajesh Rajput

2013-01-01

Full Text Available Existing treatment modalities for Graves′ disease includes antithyroid drugs (ATDs, radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves′ disease after discussing this with the patient.

Indefinite antithyroid drug therapy in toxic Graves’ disease: What are the cons

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Rajput, Rajesh; Goel, Vasudha

2013-01-01

Existing treatment modalities for Graves’ disease includes antithyroid drugs (ATDs), radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves’ disease after discussing this with the patient. PMID:24251229

STEM CELL TRANSPLANTATION AS A POSSIBLE STRATEGY FOR TREATING STANDARD THERAPY-RESISTANT ANKYLOSING SPONDYLITIS

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I. Z. Gaidukova

2016-01-01

Full Text Available The authors have analyzed the literature dealing with studies of the efficiency and safety of stem cell transplantation (SCT in patients with ankylosing spondylitis (AS through the electronic resources Pubmed and Medline by using the keywords «bone marrow transplantation», «hematopoietic stem cell transplantation», «ankylosing spondylitis», «autoimmune diseases», and «sacroiliac joint biopsy». The paper describes four cases of SCT in AS patients, including transplantation that was carried out in one patient with lymphoma concurrent with AS, in two AS patients without blood cancers, and in one patient with AS concurrent with myeloid leukemia. Drug-free remission was achieved in 3 cases: lymphoma concurrent with AS (n=1, AS concurrent with myeloid leukemia (n=1, and AS without comorbidities (n=1. In addition to an improvement in the course of AS, there were also two cases with clinical presentations of AS after SCT. The given cases show that SCT can be basically used to induce drug-free remission in patients with severe forms of standard therapy-resistant AS. However, the introduction of SCT in clinical practice needs to adjust the technique to the specific features of AS patients. 

Molecular fundamentals of drug interactions in the therapy of colorectal cancer

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Katarzyna Regulska

2014-03-01

Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

3D mathematical modeling of glioblastoma suggests that transdifferentiated vascular endothelial cells mediate resistance to current standard-of-care therapy

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Yan, Huaming; Romero-López, Mónica; Benitez, Lesly I.; Di, Kaijun; Frieboes, Hermann B.; Hughes, Christopher C. W.; Bota, Daniela A.; Lowengrub, John S.

2017-01-01

Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, crosstalk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Further, GSC also transdifferentiate into bona-fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional anti-angiogenic therapies. Here we use 3D mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSC drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with anti-angiogenic therapies, reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSC and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GEC maintain GSC. Our study suggests that a combinatorial regimen targeting the vasculature, GSC, and GEC, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. PMID:28536277

33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

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2010-07-01

... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

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Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

What works in addiction treatment and what doesn't: is the best therapy no therapy?

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Peele, S

The current trend toward treating drug and alcohol (and other) addictions in disease-oriented, 12-step programs has had less success than most people believe. Treatments that teach coping skills, mobilize community forces, and instill values toward prosocial behavior have had success rates far superior to therapies that instruct individuals that they take drugs or drink excessively because they have a disease or because drugs are inherently addictive. Successful treatments instead deal with addicts' interactions with their environments and help them develop beliefs in their self-efficacy. Nonetheless, even addiction treatments which have demonstrated success face limitations in their ability to confront individual intentions and values, community standards, and environmental pressures and opportunities. At the same time, more individuals have quit addictions on their own than have been successfully treated by even the best therapies. Put simply, no therapy will ever be able in itself to make a substantial impact on our drug and alcohol or other addictive problems. In the meantime, addiction treatment is becoming more pervasive and coercive, and today holds out the possibility of corrupting our society and the self-conceptions of its members.

Rational use and interpretation of urine drug testing in chronic opioid therapy.

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Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L

2007-01-01

Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

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Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

Do the recommended standards for in vitro biopharmaceutic classification of drug permeability meet the "passive transport" criterion for biowaivers?

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Žakelj, Simon; Berginc, Katja; Roškar, Robert; Kraljič, Bor; Kristl, Albin

2013-01-01

BCS based biowaivers are recognized by major regulatory agencies. An application for a biowaiver can be supported by or even based on "in vitro" measurements of drug permeability. However, guidelines limit the application of biowaivers to drug substances that are transported only by passive mechanisms. Regarding published permeability data as well as measurements obtained in our institution, one can rarely observe drug substances that conform to this very strict criterion. Therefore, we measured the apparent permeability coefficients of 13 drugs recommended by FDA's Guidance to be used as standards for "in vitro" permeability classification. The asymmetry of permeability data determined for both directions (mucosal-to-serosal and serosalto- mucosal) through the rat small intestine revealed significant active transport for four out of the nine high-permeability standards and for all four low-permeability standard drugs. As could be expected, this asymmetry was abolished at 4°C on rat intestine. The permeability of all nine high-permeability, but none of the low permeability standards, was also much lower when measured with intestinal tissue, Caco-2 cell monolayers or artificial membranes at 4°C compared to standard conditions (37°C). Additionally, concurrent testing of several standard drugs revealed that membrane transport can be affected by the use of internal permeability standards. The implications of the results are discussed regarding the regulatory aspects of biopharmaceutical classification, good practice in drug permeability evaluation and regarding the general relevance of transport proteins with broad specificity in drug absorption.

Drug Improves Birth Rates for Women with Ovary Disorder

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... NIH Research Matters July 21, 2014 Drug Improves Birth Rates for Women with Ovary Disorder At a ... more effective than standard therapy in increasing live births for women with polycystic ovary syndrome. Letrozole could ...

HSA/PSS coated gold nanorods as thermo-triggered drug delivery vehicles for combined cancer photothermal therapy and chemotherapy

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Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

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Mijnhout, G S; Franken, A A M

2008-06-01

In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

Colchicine in therapy. State of the art and new perspectives for an old drug.

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Famaey, J P

1988-01-01

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development.

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Salazar-Méndez, Raquel; Yilmaz, Taygan; Cordero-Coma, Miguel

2016-01-01

Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches. Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research. Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

Lack of cross-reactivity of Ambien (zolpidem) with drugs in standard urine drug screens.

Science.gov (United States)

Piergies, A A; Sainati, S; Roth-Schechter, B

1997-04-01

To determine in healthy volunteers (men and women; 18 to 40 years old) the potential cross-reactivity of Ambien (zolpidem) and/or its metabolites with drugs that are screened by the Syva EMIT II and the Abbott ADx urine drug screens assays. Open-label, fixed-treatment sequence of 1 night each of treatment with zolpidem (10 mg) and temazepam (15 mg). Clinical Pharmacology Unit within a teaching hospital. Over a 24-hour period, presence or absence of positive results on the Syva EMIT II or the Abbott ADx urine drug assay system, each performed at two different laboratory assay sites. Following ingestion of zolpidem, no subject had any positive response in either laboratory to the Syva EMIT II or the Abbott ADx urine drug screen assays at 0, 4, 8, 12, and 24 hours postdose. During the same time period, all subjects had measurable zolpidem plasma concentrations at 1.5 and 8 hours postdose, with mean concentrations of 115.2 ng/mL and 30.1 ng/mL, respectively (in agreement with its half-life of 2.5 hours). The positive response rate at 10 hours after ingestion of Restoril (temazepam) among the four laboratory/assay combinations ranged from 36.8% to 73.7%, a range that is within the reported response rates for these tests. These data indicate that zolpidem will not cross-react in standard urine drug screens with benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines.

Functional Family Therapy for Young People in Treatment for Nonopioid Drug Use: A Systematic Review

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Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2018-01-01

Objectives: This review evaluates the evidence on the effects of functional family therapy (FFT) on drug abuse reduction for young people in treatment for nonopioid drug use. Data and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Results: The search yielded two…

Vibrio cholerae infection, novel drug targets and phage therapy.

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Fazil, Mobashar Hussain Urf Turabe; Singh, Durg V

2011-10-01

Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.

The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

Directory of Open Access Journals (Sweden)

Tinashe Mudzviti

2012-01-01

Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

Geriatric drug therapy and healthcare utilization in the United kingdom.

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Kennerfalk, Anita; Ruigómez, Ana; Wallander, Mari-Ann; Wilhelmsen, Lars; Johansson, Saga

2002-05-01

To describe the use of prescription drug therapy, especially polypharmacy, in an elderly general population; to relate that use to age, gender, and different types of healthcare utilization; and to investigate the influence of selection of different time windows on the result of the quantity as well as the categories of drugs used. Data on a sample of 5000 patients aged 65-90 years in 1996 were derived from the General Practice Research Database (GPRD). The population covered by GPRD is broadly representative of the UK population treated in general practice. Drug use was assessed using 2 time windows - current use of individual drugs on a random day (index date) and 1 month following the index date. Healthcare utilization was analyzed by use of information on visits to general practitioners (GPs), hospitalizations, and referrals to specialists. Women used more drugs than men; however, the prevalence of polypharmacy, defined as concomitant use of > or =5 drugs, was similar in both genders. The most frequently used therapeutic groups were cardiovascular, central nervous, and gastrointestinal system drugs. Almost 80% of both women and men visited a GP at least once a year. Overall, women used more ambulatory care services and men were hospitalized more often. Use of random date compared with 1-month period resulted in a significant underestimation of the amount of drugs used for acute conditions and, consequently, the risk of polypharmacy. The overall results confirm the findings in earlier studies suggesting that the GPRD might be a useful tool in further studies on prescription drug use among elderly persons. More information on the appropriateness of drug use is needed to prevent overuse as well as underuse of medications among the elderly.

77 FR 75177 - Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments

Science.gov (United States)

2012-12-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1172] Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments AGENCY... impact the entire class of opioid drugs or a large subcategory thereof (e.g., ER/LA opioids), such as the...

Antimalarial drug policy in India: past, present & future.

Science.gov (United States)

Anvikar, Anupkumar R; Arora, Usha; Sonal, G S; Mishra, Neelima; Shahi, Bharatendu; Savargaonkar, Deepali; Kumar, Navin; Shah, Naman K; Valecha, Neena

2014-02-01

The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

International Nuclear Information System (INIS)

Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

2010-01-01

Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

Proton-beam radiation therapy dosimetry standardization

International Nuclear Information System (INIS)

Gall, K.P.

1995-01-01

Beams of protons have been used for radiation therapy applications for over 40 years. In the last decade the number of facilities treating patients and the total number of patients being treated has begun go grow rapidly. Due to the limited and experimental nature of the early programs, dosimetry protocols tended to be locally defined. With the publication of the AAPM Task Group 20 report open-quotes Protocol for Dosimetry of Heavy Charged Particlesclose quotes and the open-quotes European Code of Practice for Proton-Beam Dosimetryclose quotes the practice of determining dose in proton-beam therapy was somewhat unified. The ICRU has also recently commissioned a report on recommendations for proton-beam dosimetry. There have been three main methods of determining proton dose; the Faraday cup technique, the ionization chamber technique, and the calorimeter technique. For practical reasons the ionization chamber technique has become the most widely used. However, due to large errors in basic parameters (e.g., W-value) is also has a large uncertainty for absolute dose. It has been proposed that the development of water calorimeter absorbed dose standards would reduce the uncertainty in absolute proton dose as well as the relative dose between megavoltage X-ray beams and proton beams. The advantages and disadvantages are discussed

A Pilot Prospective Randomized Control Trial Comparing Exercises Using Videogame Therapy to Standard Physical Therapy: 6 Months Follow-Up.

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Parry, Ingrid; Painting, Lynda; Bagley, Anita; Kawada, Jason; Molitor, Fred; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2015-01-01

Commercially available, interactive videogames that use body movements for interaction are used clinically in burn rehabilitation and have been shown to facilitate functional range of motion (ROM) but their efficacy with burn patients has not yet been proven. The purpose of this pilot randomized control study was to prospectively compare planar and functional ROM, compliance, pain, enjoyment, and exertion in pediatric burn patients receiving two types of rehabilitation therapy. Seventeen school-aged children with 31 affected limbs who demonstrated limited shoulder ROM from burn injury were randomized to receive exercises using either standard therapy ROM activities (ST) or interactive videogame therapy (VGT). Patients received 3 weeks of the designated therapy intervention twice daily. They were then given a corresponding home program of the same type of therapy to perform regularly for 6 months. Standard goniometry and three-dimensional motion analysis during functional tasks were used to assess ROM. Measures were taken at baseline, 3 weeks, 3 months, and 6 months. Pain was measured before and after each treatment session during the 3-week intervention. There was no difference in compliance, enjoyment, or exertion between the groups. Patients in both the ST and VGT groups showed significant improvement in shoulder flexion (P videogames were equally effective as traditional therapy for overall ROM gains and resulted in quicker recovery of motion with less pain experienced. Such videogames are a useful adjunct to therapy and should be considered as part of a holistic approach to rehabilitation within the hospital and at home after discharge in pediatric patients recovering from burn injury.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

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Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Cost-effectiveness-analysis: radioiodine or antithyroid drugs as first-line therapy of hyperthyroidism due to Graves' disease

International Nuclear Information System (INIS)

Dietlein, M.; Moka, D.; Dederichs, B.; Schicha, H.; Hunsche, E.; Lauterbach, K.W.

1999-01-01

Aim: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. Method: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq I-131 residual activity. Result: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. Conclusion: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake). (orig.) [de

Unfavourable effect of prolonged treatment with antithyroid drugs on radioiodine therapy outcome in Graves' hyperthyroidism

OpenAIRE

Rajić, Milena; Vlajković, Marina; Ilić, Slobodan; Stević, Miloš; Sekulić, Vladan; Zečević, Mila

2014-01-01

Radioiodine therapy (RIT) of Graves' hyperthyroidism (GH) is usually recommended after failure of primary therapy with antithyroid drugs (ATDs), which are commonly prescribed for up to 18-24 months. However, in our region, the prolonged ATDs treatment of the disease is very common. Thus, we assessed the efficacy of RIT after prolonged continual pretreatment with ATDs in Graves' hyperthyroidism. Therapy outcome using a single dose of radioiodine was evaluated after one year in 91 patients (f/m...

CAN MELATONIN BE EFFECTIVELY USED TO DIMINISH SIDE EFFECTS OF VARIOUS PSYCHOTROPIC DRUGS AND ELECTROCONVULSIVE THERAPY?

Directory of Open Access Journals (Sweden)

Roman Aleksandrovich Bekker

2017-10-01

Full Text Available Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.

Music therapy as an adjunct to standard treatment for obsessive compulsive disorder and co-morbid anxiety and depression: A randomized clinical trial.

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Shiranibidabadi, Shahrzad; Mehryar, Amirhooshang

2015-09-15

Previous studies have highlighted the potential therapeutic benefits of music therapy as an adjunct to standard care, in a variety of psychiatric ailments including mood and anxiety disorders. However, the role of music in the treatment of obsessive-compulsive disorder (OCD) have not been investigated to date. In a single-center, parallel-group, randomized clinical trial (NCT02314195) 30 patients with OCD were randomly assigned to standard treatment (pharmacotherapy and cognitive-behavior therapy) plus 12 sessions of individual music therapy (n = 15) or standard treatment only (n = 15) for one month. Maudsley Obsessive-Compulsive Inventory, Beck Anxiety Inventory, and Beck Depression Inventory-Short Form were administered baseline and after one month. Thirty patients completed the study. Music therapy resulted in a greater decrease in total obsessive score (post-intervention score: music therapy+standard treatment: 12.4 ± 1.9 vs standard treatment only: 15.1 ± 1.7, p Music therapy was significantly more effective in reducing anxiety (post-intervention score: music therapy + standard treatment: 16.9 ± 7.4 vs standard treatment only: 22.9 ± 4.6, p music therapy + standard treatment: 10.8 ± 3.8 vs standard treatment: 17.1 ± 3.7, p music therapy, as an adjunct to standard care, seems to be effective in reducing obsessions, as well as co-morbid anxiety and depressive symptoms. Copyright © 2015. Published by Elsevier B.V.

Progress in psoriasis therapy via novel drug delivery systems

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Nitha Vincent

2014-09-01

Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

Changes of serum cytokines levels after drug therapy in epileptic patients

International Nuclear Information System (INIS)

Xie Jianping; Li Suping; Xiong Gang

2004-01-01

Objective: To explore the role of the cytokines interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the neuroimmune modulation of epilepsy through measurement of the changes of the serum levels of the these cytokines after drug therapy in epileptic patients. Methods: Serum IL-2, IL-6, TNF-α levels were measured with RIA in 43 patients with epilepsy both before and after drug therapy for 3-6 months as well as 32 controls. Results: Before treatment, serum levels of these cytokines in the patients were significantly higher than those in the controls (p<0.001). After treatment, 18 of the 43 patients were regarded as treatment very successful, with attack numbers decreased more than 75%. Some of this group of patient had their serum cytokines levels significantly dropped down, but the mean level for the group as a whole did not change much. In the rest 25 patients with less successful result, changes were not significant with the levels increased in a few cases. Among the cytokines, levels of IL-2 were significantly positively correlated to those of IL-6 and TNF-α (r=0.47, p<0.01, r=0.55, p<0.01). Conclusion: Increased levels of the cytokines in the epileptic patients suggest an activated immune state. However, the changes of levels after therapy are not predictable and do not necessarily drop down significantly even with very successful treatment

Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

International Nuclear Information System (INIS)

2016-01-01

Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

Effectiveness of Cognitive-Behavioral Therapy in the Improvement of Coping Strategies and Addiction Symptoms in Drug-Dependent Patients

Directory of Open Access Journals (Sweden)

H BrockieMilan

2014-12-01

Full Text Available Objective: This study was carried out to determine the effectiveness of cognitive-behavioral therapy in improving coping strategies and symptoms of drug addiction patients. Method: In a quasi-experimental study, the number of 90drug-dependent patients referring to clinics to stop taking drugs existing in the city of Urmia were divided into two experimental (n=45 groups and control (n=45 using random sampling. The experimental group received 12 sessions of cognitive-behavioral treatment in Carroll style while the control group received only methadone and the physical pills. All the participants completed coping strategies questionnaire at the beginning, during (after three months, and three months after treatment (follow-up. As well, they were assessed for the rate of improvement in symptoms of addiction and process of addiction treatment using by Madzly’s addiction profile questionnaire. Findings: The results proved the effectiveness of cognitive-behavioral therapy and its survival. Conclusion: Cognitive behavioral therapy is very influential in the boost of coping strategies and the improvement of mental and physical health in drug-dependent patients.

Poly(acrylic acid) conjugated hollow mesoporous carbon as a dual-stimuli triggered drug delivery system for chemo-photothermal synergistic therapy

Energy Technology Data Exchange (ETDEWEB)

Li, Xian; Liu, Chang; Wang, Shengyu; Jiao, Jian; Di, Donghua; Jiang, Tongying; Zhao, Qinfu, E-mail: zqf021110505@163.com; Wang, Siling, E-mail: silingwang@syphu.edu.cn

2017-02-01

In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment. The DOX loaded DOX/HMC-SS-PAA had a high drug loading amount up to 51.9%. The in vitro drug release results illustrated that DOX/HMC-SS-PAA showed redox and pH dual-responsive drug release, and the release rate could be further improved by the near infrared (NIR) irradiation. Cell viability experiment indicated that DOX/HMC-SS-PAA had a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This work suggested that HMC-SS-PAA exhibited dual-responsive drug release property and could be used as a NIR-adsorbing drug delivery system for chemo-photothermal synergistic therapy. - Highlights: • Poly(acrylic acid) was grafted on hollow mesoporous carbon (HMC) via disulfide bonds. • The grafted PAA could increase the biocompatibility and stability of HMC. • The DOX-loaded DOX/HMC-SS-PAA had a high drug loading efficiency up to 51.9%. • DOX/HMC-SS-PAA showed redox/pH dual-responsive and NIR-triggered drug release. • DOX/HMC-SS-PAA showed a chemo/photothermal synergistic therapy effect.

Poly(acrylic acid) conjugated hollow mesoporous carbon as a dual-stimuli triggered drug delivery system for chemo-photothermal synergistic therapy

International Nuclear Information System (INIS)

Li, Xian; Liu, Chang; Wang, Shengyu; Jiao, Jian; Di, Donghua; Jiang, Tongying; Zhao, Qinfu; Wang, Siling

2017-01-01

In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment. The DOX loaded DOX/HMC-SS-PAA had a high drug loading amount up to 51.9%. The in vitro drug release results illustrated that DOX/HMC-SS-PAA showed redox and pH dual-responsive drug release, and the release rate could be further improved by the near infrared (NIR) irradiation. Cell viability experiment indicated that DOX/HMC-SS-PAA had a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This work suggested that HMC-SS-PAA exhibited dual-responsive drug release property and could be used as a NIR-adsorbing drug delivery system for chemo-photothermal synergistic therapy. - Highlights: • Poly(acrylic acid) was grafted on hollow mesoporous carbon (HMC) via disulfide bonds. • The grafted PAA could increase the biocompatibility and stability of HMC. • The DOX-loaded DOX/HMC-SS-PAA had a high drug loading efficiency up to 51.9%. • DOX/HMC-SS-PAA showed redox/pH dual-responsive and NIR-triggered drug release. • DOX/HMC-SS-PAA showed a chemo/photothermal synergistic therapy effect.

Liposomes as a drug delivery system in photodynamic therapy for colon cancer treatment

CSIR Research Space (South Africa)

Maduray, K

2010-01-01

Full Text Available Photodynamic therapy (PDT) uses a drug termed a photosensitizer (PS), light (laser) of an appropriate wavelength and molecular oxygen (tissue) to elicit cell death of cancer cells. The objective of this study was to evaluate the enhancement of PDT...

Monitoring early tumor response to drug therapy with diffuse optical tomography

Science.gov (United States)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

Science.gov (United States)

Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

2014-08-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

DNA Nanotechnology for Precise Control over Drug Delivery and Gene Therapy.

Science.gov (United States)

Angell, Chava; Xie, Sibai; Zhang, Liangfang; Chen, Yi

2016-03-02

Nanomedicine has been growing exponentially due to its enhanced drug targeting and reduced drug toxicity. It uses the interactions where nanotechnological components and biological systems communicate with each other to facilitate the delivery performance. At this scale, the physiochemical properties of delivery systems strongly affect their capacities. Among current delivery systems, DNA nanotechnology shows many advantages because of its unprecedented engineering abilities. Through molecular recognition, DNA nanotechnology can be used to construct a variety of nanostructures with precisely controllable size, shape, and surface chemistry, which can be appreciated in the delivery process. In this review, different approaches that are currently used for the construction of DNA nanostructures are reported. Further, the utilization of these DNA nanostructures with the well-defined parameters for the precise control in drug delivery and gene therapy is discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A 37-year-old woman presenting with impaired visual function during antituberculosis drug therapy: a case report

Directory of Open Access Journals (Sweden)

Ayanniyi Abdulkabir A

2011-07-01

Full Text Available Abstract Introduction Combination antituberculosis drug therapy remains the mainstay of treating tuberculosis. Unfortunately, antituberculosis drugs produce side effects including (toxic impaired visual function, which may be irreversible. We report a case of antituberculosis-drug-induced impaired visual function that was reversed following early detection and attention. Case presentation A 37-year-old Yoruba woman, weighing 48 kg, presented to our facility with impaired visual functions and mild sensory polyneuropathy in about the fourth month of antituberculosis treatment. Her therapy comprised ethambutol 825 mg, isoniazid 225 mg, rifampicin 450 mg, and pyrazinamide 1200 mg. Her visual acuity was 6/60 in her right eye and 1/60 in her left eye. She had sluggish pupils, red-green dyschromatopsia, hyperemic optic discs and central visual field defects. Her intraocular pressure was 14 mmHg. Her liver and kidney functions were essentially normal. Screening for human immunodeficiency virus was not reactive. Her impaired visual function improved following prompt diagnosis and attention, including the discontinuation of medication. Conclusions The ethambutol and isoniazid in antituberculosis medication are notorious for causing impaired visual function. The diagnosis of ocular toxicity from antituberculosis drugs should never be delayed, and should be possible with the patient's history and simple but basic eye examinations and tests. Tight weight-based antituberculosis therapy, routine peri-therapy visual function monitoring towards early detection of impaired function, and prompt attention will reduce avoidable ocular morbidity.

Association of opioid agonist therapy with lower incidence of hepatitis C virus infection in young adult injection drug users.

Science.gov (United States)

Tsui, Judith I; Evans, Jennifer L; Lum, Paula J; Hahn, Judith A; Page, Kimberly

2014-12-01

Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for

Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse: A Systematic Review and Meta-Analysis

Science.gov (United States)

Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2018-01-01

Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

Innovating cystic fibrosis clinical trial designs in an era of successful standard of care therapies.

Science.gov (United States)

VanDevanter, Donald R; Mayer-Hamblett, Nicole

2017-11-01

Evolving cystic fibrosis 'standards of care' have influenced recent cystic fibrosis clinical trial designs for new therapies; care additions/improvements will require innovative trial designs to maximize feasibility and efficacy detection. Three cystic fibrosis therapeutic areas (pulmonary exacerbations, Pseudomonas aeruginosa airway infections, and reduced cystic fibrosis transmembrane conductance regulator [CFTR] protein function) differ with respect to the duration for which recognized 'standards of care' have been available. However, developers of new therapies in all the three areas are affected by similar challenges: standards of care have become so strongly entrenched that traditional placebo-controlled studies in cystic fibrosis populations likely to benefit from newer therapies have become less and less feasible. Today, patients/clinicians are more likely to entertain participation in active-comparator trial designs, that have substantial challenges of their own. Foremost among these are the selection of 'valid' active comparator(s), estimation of a comparator's current clinical efficacy (required for testing noninferiority hypotheses), and effective blinding of commercially available comparators. Recent and future cystic fibrosis clinical trial designs will have to creatively address this collateral result of successful past development of effective cystic fibrosis therapies: patients and clinicians are much less likely to accept simple, placebo-controlled studies to evaluate future therapies.

The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines.

Science.gov (United States)

Poirier, A F; Murphy, W R

2016-12-01

The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al. 1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Effects of music therapy on drug avoidance self-efficacy in patients on a detoxification unit: a three-group randomized effectiveness study.

Science.gov (United States)

Silverman, Michael J

2014-01-01

Self-efficacy is a component of Bandura's social cognitive theory and can lead to abstinence and a reduction of relapse potential for people who have substance abuse disorders. To date, no music therapy researcher has utilized this theoretical model to address abstinence and reduce the likelihood of relapse in people who have addictions. The purpose of this study was to determine the effects of music therapy on drug avoidance self-efficacy in a randomized three-group wait-list control design with patients on a detoxification unit. Participants (N = 131) were cluster randomized to one of three single-session conditions: music therapy, verbal therapy, or wait-list control. Music therapy participants received a group lyric analysis intervention, verbal therapy participants received a group talk therapy session, and wait-list control participants eventually received a group recreational music therapy intervention. Although there was no significant between-group difference in drug avoidance self-efficacy, participants in the music therapy condition tended to have the highest mean drug avoidance self-efficacy scores. Posttest written comments supported the use of both music therapy and verbal therapy sessions. Two music therapy participants specifically noted that their initial skepticism had dissipated after receiving music therapy. Despite a lack of significant differences, the theoretical support of self-efficacy for substance abuse rehabilitation suggests that this may be an area of continued clinical focus and empirical investigation. Clinical anecdotes, limitations of the study, and suggestions for future research are provided.

Development of a standardized, citywide process for managing smart-pump drug libraries.

Science.gov (United States)

Walroth, Todd A; Smallwood, Shannon; Arthur, Karen; Vance, Betsy; Washington, Alana; Staublin, Therese; Haslar, Tammy; Reddan, Jennifer G; Fuller, James

2018-06-15

Development and implementation of an interprofessional consensus-driven process for review and optimization of smart-pump drug libraries and dosing limits are described. The Indianapolis Coalition for Patient Safety (ICPS), which represents 6 Indianapolis-area health systems, identified an opportunity to reduce clinically insignificant alerts that smart infusion pumps present to end users. Through a consensus-driven process, ICPS aimed to identify best practices to implement at individual hospitals in order to establish specific action items for smart-pump drug library optimization. A work group of pharmacists, nurses, and industrial engineers met to evaluate variability within and lack of scrutiny of smart-pump drug libraries. The work group used Lean Six Sigma methodologies to generate a list of key needs and barriers to be addressed in process standardization. The group reviewed targets for smart-pump drug library optimization, including dosing limits, types of alerts reviewed, policies, and safety best practices. The work group also analyzed existing processes at each site to develop a final consensus statement outlining a model process for reviewing alerts and managing smart-pump data. Analysis of the total number of alerts per device across ICPS-affiliated health systems over a 4-year period indicated a 50% decrease (from 7.2 to 3.6 alerts per device per month) after implementation of the model by ICPS member organizations. Through implementation of a standardized, consensus-driven process for smart-pump drug library optimization, ICPS member health systems reduced clinically insignificant smart-pump alerts. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

Science.gov (United States)

Zafari, Zafar; Sadatsafavi, Mohsen; Marra, Carlo A; Chen, Wenjia; FitzGerald, J Mark

2016-01-01

Bronchial thermoplasty (BT) is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy. To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA. A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]). A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs) and exacerbations as the outcomes. For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER) of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP) of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI) was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%. Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes cost

Cost-Effectiveness of Bronchial Thermoplasty, Omalizumab, and Standard Therapy for Moderate-to-Severe Allergic Asthma.

Directory of Open Access Journals (Sweden)

Zafar Zafari

Full Text Available Bronchial thermoplasty (BT is a recently developed treatment for patients with moderate-to-severe asthma. A few studies have suggested the clinical efficacy of this intervention. However, no study has evaluated the cost-effectiveness of BT compared to other alternative treatments for moderate-to-severe allergic asthma, which currently include omalizumab and standard therapy.To evaluate the cost-effectiveness of standard therapy, BT, and omalizumab for moderate-to-severe allergic asthma in the USA.A probabilistic Markov model with weekly cycles was developed to reflect the course of asthma progression over a 5-year time horizon. The study population was adults with moderate-to-severe allergic asthma whose asthma remained uncontrolled despite using high-dose inhaled corticosteroids (ICS, with or without long-acting beta-agonists [LABA]. A perspective of the health-care system was adopted with asthma-related costs as well as quality-adjusted life years (QALYs and exacerbations as the outcomes.For standard therapy, BT, and omalizumab, the discounted 5-year costs and QALYs were $15,400 and 3.08, $28,100 and 3.24, and $117,000 and 3.26, respectively. The incremental cost-effectiveness ratio (ICER of BT versus standard therapy and omalizumab versus BT was $78,700/QALY and $3.86 million/QALY, respectively. At the willingness-to-pay (WTP of $50,000/QALY and $100,000/QALY, the probability of BT being cost-effective was 9%, and 67%, respectively. The corresponding expected value of perfect information (EVPI was $155 and $1,530 per individual at these thresholds. In sensitivity analyses, increasing the costs of BT from $14,900 to $30,000 increased its ICER relative to standard therapy to $178,000/QALY, and decreased the ICER of omalizumab relative to BT to $3.06 million/QALY. Reducing the costs of omalizumab by 25% decreased its ICER relative to BT by 29%.Based on the available evidence, our study suggests that there is more than 60% chance that BT becomes

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

Science.gov (United States)

Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

2017-08-01

In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial.

Science.gov (United States)

Young, James R; Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-07-10

Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4-16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2-3 weeks postintervention. The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

Science.gov (United States)

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

Science.gov (United States)

Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

2003-12-01

The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

Are the effects of a non-drug multimodal activation therapy of dementia sustainable? Follow-up study 10 months after completion of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Luttenberger Katharina

2012-12-01

Full Text Available Abstract Background Little is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy. Methods This randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n = 52 with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardised intervention, MAKS, consisted of motor stimulation, practice of activities of daily living (ADLs, and cognitive stimulation. Each group of 10 patients was treated for 2 h, 6 days a week for 12 months. Control patients received standard nursing home care. At baseline, at the end of therapy (month 12, and 10 months thereafter (month 22, cognitive functioning was assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale, and the ability to perform ADLs was assessed using the Erlangen Test of Activities of Daily Living. Results During the therapy phase, the MAKS patients maintained their cognitive function and ability to carry out ADLs. After the end of therapy, both the control and the MAKS groups deteriorated in both their cognitive function (control, p = 0.02; MAKS, p 0: βMAKS + βMAKS month 22 = 0; χ2 = 3.8568, p = 0.0496. Cohen’s d for the difference between the two groups in ADLs and cognitive abilities 10 months after the end of therapy was 0.40 and 0.22, respectively. Conclusions A multimodal non-drug therapy of dementia resulted in stabilisation of the ability to perform ADLs, even beyond the end of therapy. To prevent functional decline for as long as possible, therapy should be performed continuously until the benefit for the patient ends. Follow-up studies on larger numbers of patients are needed to definitively confirm these results. Trial registration http://www.isrctn.com Identifier: ISRCTN

Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report

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Servadei Franco

2010-04-01

Full Text Available Abstract Background Management of glioblastoma multiforme (GBM has been difficult using standard therapy (radiation with temozolomide chemotherapy. The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI. Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Methods Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET. Results After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy. Conclusion This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed

Antimalarial drug policy in India: Past, present & future

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Anupkumar R Anvikar

2014-01-01

Full Text Available The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

Physical therapy with drug treatment in Bell palsy: a focused review.

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Ferreira, Margarida; Marques, Elisa E; Duarte, José A; Santos, Paula C

2015-04-01

The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

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Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

2018-08-01

The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

Drug-resistant tuberculosis: emerging treatment options

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Adhvaryu MR

2011-12-01

Full Text Available Meghna Adhvaryu1, Bhasker Vakharia21Department of Biotechnology, SRK Institute of Computer Education and Applied Sciences, 2R&D, Bhuma Research in Ayurvedic and Herbal Medicine, Surat, Gujarat, IndiaAbstract: Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug–drug interactions in patients coinfected with human immunodeficiency virus (HIV, inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drug-susceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and

Prolonged Intermittent Renal Replacement Therapy.

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Edrees, Fahad; Li, Tingting; Vijayan, Anitha

2016-05-01

Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Caramiphen edisylate as Adjunct to Standard Therapy attenuates soman-induced Seizures and Cognitive Deficits in Rats

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2014-06-16

705. Maren S. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats. Eur J Neurosci 2008;28... conditioning . Hear Res 2011;274:61–74. Weissman BA, Raveh L. Therapy against organophosphate poisoning: the importance of anticholinergic drugs with...whichmay lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

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Nadia Bakkour

2007-10-01

Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

Effectiveness of group cognitive therapy about opium addict complications on attitude of adolescents with drug dependent parents

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Kaveh Hojjat

2015-12-01

Full Text Available Background and Aim: Statistics show that 30% to 40 % of  opium addicted fathers’ children are prone to substance abuse in the future. The present study aimed at assessing the effectiveness of cognitive therapy approach  to attitude changing of adolescents with substance dependent fathers. Materials and Methods:  In this controlled. field-trail randomized study. .data collection tool was “attitude to addiction questionnaire”. The study population was all male students in the first grade of high school in Maneh - Samalghan city. . Six sessions of group cognitive therapy based on the effectiveness of drug side-effects in drug-addicted fathers’ adolescent children’s attitude were held. The above-mentioned questionnaire was filled out before and after intervention. The obtained data  was fed into SPSS software (V: 16 using. Independent t-test .and paired t-test were used for analysis and P<0.05 was taken as the significant level. Results:  There were no significant differences between the two groups in pre-test regarding their attitude about drug abuse (P=.20%. Mean score variance from pre-test to post-test in the intervention group decreased, but in the control group, it showed a slight increase. This means that the intervention reduced the positive attitude towards drugs, but the changes were not statistically significant (p=0.57. Besides, among ten factors decisive in an individual’s attitude about addiction, only group cognitive therapy  was able  to decrease mean points of an individual’s attitude about drug abuse .. Significantly (P = 0.04. Conclusion: It was found that group cognitive therapy education about opium  addict complicationsdidn`t have a significant effect on the attitude of the students with addicted fathers. Thus, a change of adolescents’ attitude requires more research.

Application of a drug delivery system using ultrasound and nano/microbubbles for anti-angiogenic therapy

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Horie, Sachiko; Kodama, Tetsuya; Sato, Yasushi

2017-01-01

The drug delivery system using ultrasound and nano/microbubbles is a molecular delivery approach using the mechanism of sonoporation. With sonoporation, an endothelium-derived negative-feedback regulator of angiogenesis, Vasohibin-1 (VASH1), was introduced specifically into tumor vessels. We found VASH1 in tumor vessels induce normalization of tumor vessels and inhibited tumor growth. A recent topic regarding tumor angiogenesis is vascular normalization. Tumor vessels are abnormal or immature that cause hyperpermeability and impaired blood flow. Tumor vascular normalization improves blood flow and tissue hypoxia, which increase the effectiveness of chemotherapy and radiotherapy and reduce tumor cell malignancy. In this review, application of drug delivery system using ultrasound for an anti-angiogenic therapy, a tumor vessel normalization therapy to treat cancer, is summarized. (author)

Inhalation Therapy in Horses.

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Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognosis of medical and economic efficiency of a patient-oriented program implementation aimed at formation of adherenceto drug therapy among rural population

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E A Kitaeva

2018-02-01

Full Text Available Aim. Development and implementation of novel organizational management technologies of medical care aimed at formation of adherence to drug therapy in patients from rural areas and calculation of medical and economic efficiency of implementation of this project. Methods. The study subject was the population of Rybnaya Sloboda district of the Republic of Tatarstan. Patient recruitment into the groups was conducted in the polyclinic of Rybnaya Sloboda central regional hospital. The duration of the study was 6 months for each of two groups with further follow-up and evaluation of adherence to therapy for 2 months. Results. Annually stroke affects 5.6 to 6.6 million of people around the world, 35% of whom die in the acute period. Recently, serious rejuvenation of cardiovascular disorders has been observed. The main reason for such trend is low patients’ compliance to drug therapy. And patients’ compliance itself allows significantly decreasing the risk of cardiovascular complications. The article discussed the issues of low compliance to drug therapy, presents the methods of its formation in patients from rural area. The examples of foreign and Russian experience of increasing patients’ compliance to drug therapy are described and the key intervention points for patients are determined. On the basis of conducted analysis, implementation was developed and suggested for patient-oriented program aimed at formation of adherence to drug therapy of rural population. Also, the authors performed evaluation of medical and economic efficiency of implementation of a patient-oriented program aimed at formation of adherence to drug therapy of rural population (assessment of expenditures for medications, hospital stay, incapacity related to the main disease; evaluation of expenditures for prevention of complications and disability. Conclusion. Effective organization of prophylactic activity is of great importance for prevention of cardiovascular disease

Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

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Gisbert, J P; Romano, M; Gravina, A G; Solís-Muñoz, P; Bermejo, F; Molina-Infante, J; Castro-Fernández, M; Ortuño, J; Lucendo, A J; Herranz, M; Modolell, I; Del Castillo, F; Gómez, J; Barrio, J; Velayos, B; Gómez, B; Domínguez, J L; Miranda, A; Martorano, M; Algaba, A; Pabón, M; Angueira, T; Fernández-Salazar, L; Federico, A; Marín, A C; McNicholl, A G

2015-04-01

The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed. © 2015 John Wiley & Sons Ltd.

[Development of a standardized guide for optimizing drug adherence information to be dispensed during a pharmaceutical counseling with a multiple myeloma patient: Initial validation].

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Favier-Archinard, Camille; Leguelinel-Blache, Géraldine; Dubois, Florent; Le Gall, Tanguy; Bourquard, Pascal; Passemard, Nadège; Tora, Sandrine; Rey, Aurélie; Rossi, Marie; Chevallier, Thierry; Cousin, Christelle; Favier, Mireille

2018-05-01

The safety of the community treatment with oral anticancer therapies is a strong theme of the cancer plan 2014-2019. The objective of this study was to develop a Pharmaceutical Counseling Guide to improve medication adherence in patients treated for multiple myeloma with oral anticancer therapies. A multidisciplinary professional working group selected a list of relevant medication adherence-related items that served as the framework for the design of the pharmaceutical counseling support materials in patient-accessible language. The readability, understanding and memorization of the information were validated in ten patients treated for myeloma. Twelve items were selected for treatment information (5 items), treatment planning (5 items), and adverse drug effects (2 items). A pharmacist guide, a patient guide, a medication schedule, and three self-questionnaires to evaluate medication knowledge and understanding of patients were developed. The patient test resulted in changes in these documents. This study carried out the initial validation of documents to standardize the pharmaceutical counseling for patients treated for myeloma so that it can be reproduced from one patient to another regardless of the pharmacist, by standardizing the information issued. This study needs to be completed by a final validation in myeloma patients, free from oral anticancer therapies. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma

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Bonetta A

2017-04-01

Full Text Available Alberto Bonetta,1 Giandomenico Roviello,2,3 Daniele Generali,3,4 Laura Zanotti,3 Maria Rosa Cappelletti,3 Chiara Pacifico,5 Francesco Di Pierro6 1Oncological Radiotherapy Operative Unit, ASST, Cremona, 2Department of Molecular and Translational Medicine, University of Brescia, Brescia, 3Molecular Therapy and Pharmacogenomics Unit, ASST, Cremona, 4Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, 5Department of Medical, Surgical and Neurological Sciences, University Hospital of Siena, Siena, 6Velleja Research Scientific Department, Milan, Italy Introduction: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs. Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370® in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID and antibiotic use during radiotherapy for prostate carcinoma was evaluated. Methods: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489 or not (n=435 the enteric-coated, highly standardized cranberry extract for 6–7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann–Whitney U test and Pearson’s X2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria. Results: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

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Germovsek, Eva; Barker, Charlotte I S; Sharland, Mike; Standing, Joseph F

2018-04-19

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies.

IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer.

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Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

2016-04-17

Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

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Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

2016-05-01

Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

Mechanisms of termination and prevention of atrial fibrillation by drug therapy

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Workman, AJ; Smith, GL; Rankin, AC

2011-01-01

Atrial fibrillation (AF) is a disorder of the rhythm of electrical activation of the cardiac atria. It is the most common cardiac arrhythmia, has multiple aetiologies, and increases the risk of death from stroke. Pharmacological therapy is the mainstay of treatment for AF, but currently available anti-arrhythmic drugs have limited efficacy and safety. An improved understanding of how anti-arrhythmic drugs affect the electrophysiological mechanisms of AF initiation and maintenance, in the setting of the different cardiac diseases that predispose to AF, is therefore required. A variety of animal models of AF has been developed, to represent and control the pathophysiological causes and risk factors of AF, and to permit the measurement of detailed and invasive parameters relating to the associated electrophysiological mechanisms of AF. The purpose of this review is to examine, consolidate and compare available relevant data on in-vivo electrophysiological mechanisms of AF suppression by currently approved and investigational anti-arrhythmic drugs in such models. These include the Vaughan Williams class I-IV drugs, namely Na+ channel blockers, β-adrenoceptor antagonists, action potential prolonging drugs, and Ca2+ channel blockers; the “upstream therapies”, e.g., angiotensin converting enzyme inhibitors, statins and fish oils; and a variety of investigational drugs such as “atrial-selective” multiple ion channel blockers, gap junction-enhancers, and intracellular Ca2+-handling modulators. It is hoped that this will help to clarify the main electrophysiological mechanisms of action of different and related drug types in different disease settings, and the likely clinical significance and potential future exploitation of such mechanisms. PMID:21334377

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

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Michaela Thomas

2017-11-01

Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

[Development of legislation and standardization of acupuncture therapy in the United States of America].

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Wang, Shou-Dong; Hou, You-Juan; Meng, Fan-Hong; Chen, Shu-Juan; Wang, Yan-Yao; Jiang, Fan; Ding, Ming

2012-06-01

In the present article, the authors summarized the state of acupuncture therapy in the United States of America from 1) history and current state, 2) legislation and its contents, management system and introduction of health insurance system, and 3) standardization. Acupuncture therapy, as a complementary or alternative therapy, has been widely supported and approved by majority of states in the USA. The authors hold that due to differences between the oriental and western cultures and difficulties of Chinese medicine in quantitative and qualitative studies, the legislation on acupuncture therapy for approval of the American Parliament needs paying more efforts.

A controlled evaluation of family behavior therapy in concurrent child neglect and drug abuse.

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Donohue, Brad; Azrin, Nathan H; Bradshaw, Kelsey; Van Hasselt, Vincent B; Cross, Chad L; Urgelles, Jessica; Romero, Valerie; Hill, Heather H; Allen, Daniel N

2014-08-01

Approximately 50% of child protective service (CPS) referrals abuse drugs; yet, existing treatment studies in this population have been limited to case examinations. Therefore, a family-based behavioral therapy was evaluated in mothers referred from CPS for child neglect and drug abuse utilizing a controlled experimental design. Seventy-two mothers evidencing drug abuse or dependence and child neglect were randomly assigned to family behavior therapy (FBT) or treatment as usual (TAU). Participants were assessed at baseline, 6 months, and 10 months postrandomization. As hypothesized, intent-to-treat repeated measures analyses revealed mothers referred for child neglect not due to their children being exposed to illicit drugs demonstrated better outcomes in child maltreatment potential from baseline to 6- and 10-month postrandomization assessments when assigned to FBT, as compared with TAU mothers and FBT mothers who were referred due to child drug exposure. Similar results occurred for hard drug use from baseline to 6 and 10 months postrandomization. However, TAU mothers referred due to child drug exposure were also found to decrease their hard drug use more than TAU mothers of non-drug-exposed children and FBT mothers of drug-exposed children at 6 and 10 months postrandomization. Although effect sizes for mothers assigned to FBT were slightly larger for marijuana use than TAU (medium vs. large), these differences were not statistically significant. Specific to secondary outcomes, mothers in FBT, relative to TAU, increased time employed from baseline to 6 and 10 months postrandomization. Mothers in FBT, compared to TAU, also decreased HIV risk from baseline to 6 months postrandomization. There were no differences in outcome between FBT and TAU for number of days children were in CPS custody and alcohol intoxication, although FBT mothers demonstrated marginal decreases (p = .058) in incarceration from baseline to 6 months postrandomization relative to TAU mothers

Cost-effectiveness analysis of antithyroid drug therapy, 131I therapy and subtotal thyroidectomy for Graves' disease

International Nuclear Information System (INIS)

Yano, Fuzuki; Watanabe, Sadahiro; Hayashi, Katsumi; Kita, Tamotsu; Yamamoto, Masayoshi; Kosuda, Shigeru; Tanaka, Yuji

2007-01-01

The objective of this study was to assess the cost-effectiveness of antithyroid drug (ATD) therapy vs. radioiodine therapy (RIT) vs. subtotal thyroidectomy (STT) by calculating expected lifelong cost and utility based on Graves' disease patients' responses to questionnaires using a decision-tree sensitivity analysis and relevant variables. The decision-tree sensitivity analysis to determine expected lifelong cost and utility in Graves' disease patients was designed on the basis of the 4 competing strategies consisting of: (1) ATD therapy plus RIT strategy, (2) ATD therapy plus STT strategy, (3) low-fixed-dose (185 MBq) RIT alone strategy, and (4) high-fixed-dose (370 MBq) RIT alone strategy. One-way sensitivity analysis was designed in the ATD therapy plus RIT strategy, for replacement with RIT in place of ATD, ranging from a 1% incidence of ATD side effects to 30%. The low-fixed-dose RIT alone strategy was least costly, and the high-fixed-dose RIT alone strategy most costly. The lifelong utility of high-fixed-dose RIT alone strategy with a 5% rate of discounting was highest (lifelong utility for 30 years: 15.2/patient), and the utility of the ATD plus RIT strategy with 1% side effects of the ATD was lowest (14.1/patient). The cost-effectiveness ratio was lowest (yen 5 008/utility) in a low-fixed-dose RIT alone strategy. In conclusion, a low-fixed-dose RIT alone strategy is preferred treatments in view of cost-effectiveness ratio, and RIT should be used more widely in Japan. (author)

Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

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Stimson Gerry V

2006-03-01

Full Text Available Abstract Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs. Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups

[Treatment of typical trigeminus neuralgias. Overview of the current state of drug and surgical therapy].

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Möbius, E; Leopold, H C; Paulus, W M

1984-10-11

Carbamazepine continues to be the most useful drug in the treatment of trigeminal neuralgia. Diphenylhydantoin may be given in addition to or instead of Carbamazepine. Refractory cases may benefit from combination with Baclofen or Chlorphenesin. In cases of persistent pain the concomitant use of tricyclic antidepressant drugs is recommended. If pain continues in spite of multiple medical therapies or if serious side effects develop, then surgical procedures such as percutaneous controlled thermocoagulation or microvascular decompression are indicated. Percutaneous thermocoagulation is associated with the lowest mortality and morbidity rate and can easily be repeated. Microvascular decompression should especially be offered to young patients, who want to avoid any sensory disturbance of the face, and recommended for other patients for whom all other forms of therapy including percutaneous thermocoagulation have failed.

Drug delivery system design and development for boron neutron capture therapy on cancer treatment

International Nuclear Information System (INIS)

Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

2014-01-01

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

Data Decision and Drug Therapy Based on Non-Small Cell Lung Cancer in a Big Data Medical System in Developing Countries

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Jia Wu

2018-05-01

Full Text Available In many developing or underdeveloped countries, limited medical resources and large populations may affect the survival of mankind. The research for the medical information system and recommendation of effective treatment methods may improve diagnosis and drug therapy for patients in developing or underdeveloped countries. In this study, we built a system model for the drug therapy, relevance parameter analysis, and data decision making in non-small cell lung cancer. Based on the probability analysis and status decision, the optimized therapeutic schedule can be calculated and selected, and then effective drug therapy methods can be determined to improve relevance parameters. Statistical analysis of clinical data proves that the model of the probability analysis and decision making can provide fast and accurate clinical data.

Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

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Anusuya, Shanmugam; Natarajan, Jeyakumar

2012-12-01

Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

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Feldman, Steven R; Huang, William W; Huynh, Tu T

2014-06-01

Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

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Wolbers, Marcel; Heemskerk, Dorothee; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Caws, Maxine; Farrar, Jeremy; Day, Jeremy

2011-02-02

In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design. We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the

Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

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Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-08-08

Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

PHARMACOECONOMIC ANALYSIS OF CHRONIC HEART FAILURE DRUG THERAPY IN PATIENTS WITH COMORBID CONDITIONS

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S. K. Zyryanov

2018-01-01

Full Text Available Aim. To perform pharmacoeconomic analysis of CHF therapy with supramolecular sacubitril/valsartan complex compared to routine therapy in patients with diabetes type 2 and ACE inhibitor intolerance within context of Russian healthcare system.Material and methods. A Markov model based on Russian Standards of treatment and clinical practice results was built. Cost-effectiveness analysis was done by comparing two patient groups of 1000 people each. Budget impact analysis required 27,451 simulated patients. Randomized controlled clinical trials results of sacubitril/valsartan vs. routine practice were used as source of efficacy and safety data. Time horizon was set at 3 years. Quality Adjusted Life Years (QALY were used as effectiveness. Single-factor sensitivity analysis (SA was used to ensure the results are robust to changes in market situation.Results. Cost-effectiveness ratio for sacubitril/valsartan is 301,145.7 rub. per QALY while cost-effectiveness ratio for routine practice is 510,621 rub. Budget impact analysis results indicate that during three years, in case of sacubitril/valsartan usage budgetary burden can be reduced by more than 220,000 rubles per patient and leads to savings of more than six billion rubles in terms of the whole population. Sensitivity analysis has confirmed the robustness of results.Conclusion. These results indicate benefits of sacubitril/valsartan using for CHF patients with type 2 diabetes and ACE inhibitor intolerance and justify inclusion of this drug into reimbursement lists that allow to reduce risk of hospitalization, lethal outcomes and budget of healthcare system.

Drug therapy in spinal tuberculosis.

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Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

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Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

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Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

2017-05-01

To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

Current therapy for Parkinson's disease

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A. V. Obukhova

2014-01-01

Full Text Available The main goal of therapy for Parkinson's disease (PD is to correct dopamine deficiency in the nigrostriatal system. Levodopa preparations and dopamine receptor agonists (DRAs that are prescribed with regards to patient age and disease severity are mainly used now. Notwithstanding the fact that levodopa preparations are the gold standard of therapy, their long-term use gives rise to complications as motor fluctuations and drug-induced dyskinesias. The currently available DRAs are the drugs of choice for the therapy of early-stage PD as they are as effective as levodopa preparations. In extensive-stage PD, DRAs are used to enhance the therapy and correction of developed motor fluctuations and dyskinesias. Pramipexole is one of the most commonly used representatives of non-ergoline DRAs. The paper analyzes the efficacy of the medication used as both monotherapy and part of combined therapy, its effect on tremor and depression in PD. A novel extended-release formulation of pramipexole is considered separately. Both immediate- and extended-release pramipexole formulations contain the same active ingredient and have the same dopamine-receptor interaction profile, but differ in the tablet release rate of the active ingredient. The advantages of the novel formulation are its more steady-state plasma concentration and 24-hour action, which ensures continuous dopaminergic stimulation ofpostsynaptic receptors to prevent and treat already developed motor complications. The once-daily extended-release formulation of the drug makes its treatment regimen easier and patient compliance higher.

The detection and evaluation of drug-induced changes in the gastrointestinal motility of beagle dogs using a 111In-labelled resin mixed into a standard meal as tracer

International Nuclear Information System (INIS)

Dormehl, I.C.; Du Plessis, M.; Pilloy, W.; Meyer, B.J.; Maree, M.

1985-01-01

An investigation was performed to establish the usefulness of 111 In-labelled polymer beads mixed into a standard meal as a tracer of gatrointestinal (GI)-motility changes due to the influence of various drugs. The labelled polymer beads were well mixed into the food, which was then fed to healthy beagle dogs undergoing drug therapy. GI motility was monitored using a gamma camera and data processor. The results were compared to those obtained from corresponding placebo studies on the same dogs. A significant acceleration of gastric emptying and colon transit was noted under the influence of a gastric and intestinal prokinetic coded R 51619. No influence on GI motility could, however, be detected after the administration of a calcium-blocking agent to the dogs. (orig.)

Detection and evaluation of drug-induced changes in the gastrointestinal motility of beagle dogs using a /sup 111/In-labelled resin mixed into a standard meal as tracer

Energy Technology Data Exchange (ETDEWEB)

Dormehl, I.C.; Du Plessis, M.; Pilloy, W.; Meyer, B.J.; Maree, M.

1985-03-01

An investigation was performed to establish the usefulness of /sup 111/In-labelled polymer beads mixed into a standard meal as a tracer of gatrointestinal (GI)-motility changes due to the influence of various drugs. The labelled polymer beads were well mixed into the food, which was then fed to healthy beagle dogs undergoing drug therapy. GI motility was monitored using a gamma camera and data processor. The results were compared to those obtained from corresponding placebo studies on the same dogs. A significant acceleration of gastric emptying and colon transit was noted under the influence of a gastric and intestinal prokinetic coded R 51619. No influence on GI motility could, however, be detected after the administration of a calcium-blocking agent to the dogs.

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder

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Bieleninik, Łucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J.; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo

2017-01-01

Importance Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14

Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Liu, Kuang-Kai; Wang, Chi-Ching; Chao, Jui-I [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30013, Taiwan (China); Zheng, Wen-Wei; Lo, Yu-Shiu; Chen, Chinpiao [Department of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan (China); Chiu, Yu-Chung; Cheng, Chia-Liang, E-mail: clcheng@mail.ndhu.edu.tw, E-mail: chinpiao@mail.ndhu.edu.tw, E-mail: jichao@faculty.nctu.edu.tw [Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan (China)

2010-08-06

A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 {mu}g ml{sup -1} ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.

Enzyme Replacement Therapy for Fabry Disease

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Maria Dolores Sanchez-Niño PhD

2016-11-01

Full Text Available Fabry disease is a rare X-linked disease caused by the deficiency of α-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human α-galactosidase A (agalsidase are available in most markets: agalsidase-α and agalsidase-β, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-α. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-α is 0.2 mg/kg/2 weeks, while the dose for agalsidase-β is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-β is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death. In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.

Strategies of bringing drug product marketing applications to meet current regulatory standards.

Science.gov (United States)

Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

2015-08-01

In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

Science.gov (United States)

Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

2016-05-01

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Application of the Pareto principle to identify and address drug-therapy safety issues.

Science.gov (United States)

Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

2014-06-01

Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

METHODOLOGY OF THE DRUGS MARKET VOLUME MODELING ON THE EXAMPLE OF HEMOPHILIA A

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N. B. Molchanova

2015-01-01

Full Text Available Hemophilia A is a serious genetic disease, which may lead to disability of a patient even in early ages without a required therapy. The only one therapeutic approach is a replacement therapy with drugs of bloodcoagulation factor VIII (FVIII. The modeling of coagulation drugs market volume will allow evaluation of the level of patients’ provision with a necessary therapy. Modeling of a “perfect” market of drugs and its comparison with the real one was the purpose of the study. During the modeling of market volume we have used the data about the number of hamophilia A patients on the basis of the federal registry, Russian and international morbidity indices, and the data of a real practice about average consumption of drugs of bloodcoagulation factors and data about the drugs prescription according to the standards and protocols of assistance rendering. According to the standards of care delivery, average annual volume of FVIII drugs consumption amounted to 406 325 244 IU for children and 964 578 678 IU for adults, i.e. an average volume of a “perfect” market is equal to 1 370 903 922 IU for all patients. The market volume is 1.8 times bigger than a real volume of FVIII drugs which, according to the data of IMS marketing agency, amounted to 765 000 000 IU in 2013. The modeling conducted has shown that despite a relatively high patients’ coverage there is a potential for almost double growth.

National indicators for quality of drug therapy in older persons: the Swedish experience from the first 10 years.

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Fastbom, Johan; Johnell, Kristina

2015-03-01

Inappropriate drug use is an important health problem in elderly persons. Beginning with the Beers' criteria in the early 1990s, explicit criteria have been extensively used to measure and improve quality of drug use in older people. This article describes the Swedish indicators for quality of drug therapy in the elderly, introduced in 2004 and updated in 2010. These indicators were designed to be applied to people aged 75 years and over, regardless of residence and other characteristics. The indicators are divided into drug specific, covering choice, indication and dosage of drugs, polypharmacy, drug-drug interactions (DDIs), drug use in decreased renal function and in some symptoms; and diagnosis specific, covering the rational, irrational and hazardous drug use in common disorders in elderly people. During the 10 years since introduction, the Swedish indicators have several applications. They form the basis for recommendations for drug therapy in older people, are implemented in prescribing supports and drug utilisation reviews, are used in national benchmarking of the quality of Swedish healthcare and have contributed to initiatives from pensioner organisations. The indicators have also been used in several pharmacoepidemiological studies. Since 2005, there have been signs of improvement of the quality of drug prescribing to elderly persons in Sweden. For example, the prescribing of drugs that should be avoided in older persons decreased by 36 % between 2006 and 2012 in persons aged 80 years and older. Similarly, drug combinations that may cause DDIs decreased by 26 % and antipsychotics by 41 %. The indicators have likely contributed to this.

Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy: Using Explorys in the MS Population.

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Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander

2016-01-01

Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

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Patel, Mira A.; Kim, Jennifer E.; Ruzevick, Jacob [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States); Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, 1201 Welch Rd., P309 MSLS, Stanford, CA 94305 (United States); Lim, Michael, E-mail: mlim3@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States)

2014-09-29

The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

International Nuclear Information System (INIS)

Patel, Mira A.; Kim, Jennifer E.; Ruzevick, Jacob; Li, Gordon; Lim, Michael

2014-01-01

The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders

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D'Angelo S

2017-03-01

Full Text Available Salvatore D’Angelo,1 Giuseppina Tramontano,1 Michele Gilio,1 Pietro Leccese,1 Ignazio Olivieri1,2 1Rheumatology Institute of Lucania (IRel - Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, 2Basilicata Ricerca Biomedica (BRB Foundation, Potenza, Italy Abstract: Psoriatic arthritis (PsA is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab as well as interleukin (IL-12/23 (ustekinumab and IL-17 (secukinumab inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient’s preferences (e.g., administration route, and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed. Keywords: psoriatic arthritis, treatment, biological drugs, TNF inhibitors, ustekinumab, secukinumab

Carbon dioxide therapy in the treatment of cellulite: an audit of clinical practice.

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Lee, Georgia S K

2010-04-01

The clinical practice of using carbon dioxide therapy for localized adiposities was audited over a 4-year period. Patients receiving physical, dietary, or drug concurrent therapy were excluded from the audit. Original measurements in terms of mean +/- standard error of the mean (SEM) were compared with those obtained after five sessions. This series included 101 women who underwent abdominal therapy. Significant reduction (p carboxytherapy is safe and effective.

Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial

NARCIS (Netherlands)

van Tubergen, A.; Landewé, R.; van der Heijde, D.; Hidding, A.; Wolter, N.; Asscher, M.; Falkenbach, A.; Genth, E.; Thè, H. G.; van der Linden, S.

2001-01-01

To determine the efficacy of combined spa-exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS). A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean

The application of carbon nanotubes in target drug delivery systems for cancer therapies

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Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

2011-10-01

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

Antifungal therapy: drug-drug interactions at your fingertips

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Lempers, V.J.; Bruggemann, R.J.

2016-01-01

The Information Age has revolutionized the ability of healthcare professionals (HCPs) to oversee a substantial body of clinically relevant information literally at one's fingertips. In the field of clinical pharmacology, this may be particularly useful for managing drug-drug interactions (DDIs). A

Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

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Abraham, John; Davis, Courtney

2009-08-01

Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

How we make cell therapy in Italy.

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Montemurro, Tiziana; Viganò, Mariele; Budelli, Silvia; Montelatici, Elisa; Lavazza, Cristiana; Marino, Luigi; Parazzi, Valentina; Lazzari, Lorenza; Giordano, Rosaria

2015-01-01

In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

Addressing brain tumors with targeted gold nanoparticles: a new gold standard for hydrophobic drug delivery?

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Cheng, Yu; Meyers, Joseph D; Agnes, Richard S; Doane, Tennyson L; Kenney, Malcolm E; Broome, Ann-Marie; Burda, Clemens; Basilion, James P

2011-08-22

EGF-modified Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide-targeted Au NPs. Compared to the untargeted conjugates, EGF-Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard-to-reach cancers. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation.

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Ji, Tianjiao; Zhao, Ying; Ding, Yanping; Wang, Jing; Zhao, Ruifang; Lang, Jiayan; Qin, Hao; Liu, Xiaoman; Shi, Jian; Tao, Ning; Qin, Zhihai; Nie, Guangjun; Zhao, Yuliang

2016-01-18

A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein-α (FAP-α), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug-loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP-α cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Therapeutic drug monitoring of infliximab : performance evaluation of three commercial ELISA kits

NARCIS (Netherlands)

Schmitz, E.M.H.; van de Kerkhof, D.; Hamann, D.; van Dongen, J.L.J.; Kuijper, P.H.M.; Brunsveld, L.; Scharnhorst, V.; Broeren, M.A.C.

2016-01-01

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences

Pharmacy Characteristics Associated with the Provision of Drug Therapy Services in Nonmetropolitan Community Pharmacies

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Gadkari, Abhijit S.; Mott, David A.; Kreling, David H.; Bonnarens, Joseph K.

2009-01-01

Context: Higher prevalence of chronic diseases and reduced access to other health professionals in rural areas suggest that rural Medicare enrollees will benefit from pharmacist-provided drug therapy services (DTS). Purpose: The purpose of this study was to describe non-metropolitan community pharmacy sites in Wisconsin, the provision of DTS at…

Current standard treatment for pediatric glioma patients

International Nuclear Information System (INIS)

Sonoda, Yukihiko; Kumabe, Toshihiro; Saito, Ryuta; Kanamori, Masayuki; Yamashita, Yoji; Tominaga, Teiji

2012-01-01

In this paper, we selected three representative disorders among pediatric gliomas and reviewed standard treatments for these diseases. The formation of this rare disease is involved with BRAF mutation as well as cerebellar pilocytic astrocytoma. Radical resection is not recommended as initial therapy due to high morbidity. Despite its good tumor control, radiotherapy is not a standard therapy due to neuroendocrine and neurocognitive dysfunction. Several papers have reported the effectiveness of platinum-based chemotherapy, which is a useful for induction therapy. Recent progress in molecular analyses has suggested that some markers might be used for staging ependymoma. While total resection is considered to be strongly correlated with patients' survival, the majority of recurrence occurs in the primary site. Despite many clinical trials, chemotherapeutic agents were not found to be effective for this disease. Since whole brain radiation cannot prevent dissemination, local radiation is recommended for adjuvant therapy. The prognosis of this disease is still dismal, and median survival time is within 1 year. Although clinical trials have been conducted to assess the efficacy of chemotherapy prior to, concomitantly with, or after radiotherapy, an effective regimen has not yet been established. Therefore, only conventional local radiotherapy is the standard regimen for this disease. A new therapeutic approach, such as convection-enhanced drug delivery, would be required for improved outcomes in patients with this disease. (author)

Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

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Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

2015-04-01

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

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Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

2016-01-01

With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

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Bulaj, Grzegorz; Ahern, Margaret M.; Kuhn, Alexis; Judkins, Zachary S.; Bowen, Randy C.; Chen, Yizhe

2016-01-01

Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products

Autoimmune liver disease and therapy in childhood

Directory of Open Access Journals (Sweden)

Matjaž Homan

2013-10-01

Full Text Available Autoimmune hepatitis is a chronic immune-mediated disease of the liver. In childhood, autoimmune liver disorders include autoimmune hepatitis type I and II, autoimmune sclerosing cholangitis, Coombs-positive giant cell hepatitis, and de novo autoimmune hepatitis after liver transplantation. Autoimmune liver disease has a more aggressive course in children, especially autoimmune hepatitis type II. Standard therapy is a combination of corticosteroids and azathioprine. Around 80 % of children with autoimmune liver disease show a rapid response to combination therapy. The non-responders are treated with more potent drugs, otherwise autoimmune disease progresses to cirrhosis of the liver and the child needs liver transplantation as rescue therapy.

Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

Science.gov (United States)

Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

2016-03-31

There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

Will NOACs become the new standard of care in anticoagulation therapy?

Directory of Open Access Journals (Sweden)

Ergene Oktay

2015-06-01

Full Text Available Atrial fibrillation is the most common cardiac arrhythmia in the general population, with a prevalence of 1–3%, which increases with age, reaching 15% in elderly people. Prophylaxis of ischemic stroke with warfarin was the gold standard of medical management for many years. On the other hand heparin and warfarin was the main pharmacologic agents for the prophylaxis/treatment of venous thromboembolism. In the last 5 years warfarin is getting replaced by non-vitamin K antagonist oral anticoagulants at least partly. In this article it is attempted to foresee whether new oral anticoagulants will become the new standard of care in anticoagulation therapy.

DRUG THERAPY IN THE PROGRESSED CML PATIENT WITH MULTI-TKI FAILURE

Directory of Open Access Journals (Sweden)

Ibrahim C. Haznedaroglu

2015-02-01

Full Text Available The aim of this paper is to outline pharmacotherapy of the ‘third-line management of CML’ (progressive disease course after sequential TKI drugs. Current management of CML with multi-TKI failure is reviewed. TKI (bosutinib, ponatinib, dasatinib, nilotinib and non-TKI (omacetaxine mepussecinate, IFN or PEG-IFN drugs are available. The literature search was made in PubMed with particular focus on the clinical trials, recommendations, guidelines and expert opinions, as well as international recommendations. Progressing CML disease with multi-TKI failure should be treated with alloSCT based on the availability of the donor and EBMT transplant risk scores. The TKI and non-TKI drugs shall be used to get best promising (hematological, cytogenetic, molecular response. During the CP-CML phase of multi-TKI failure, 2nd generation TKIs (nilotinib or dasatinib are used if they remained. Bosutinib and ponatinib (3rd generation TKIs can be administered in triple-TKI failed (imatinib and nilotinib and dasatinib patients. The presence of T315I mutation at any phase requires ponatinib or omacetaxine mepussecinate therapy before allografting. During the AP/BC-CML phase of multi-TKI failure, the most powerful TKI available (ponatinib or dasatinib if remained together with chemotherapy should be given before alloSCT. Monitoring of CML disease and drug off-target risks (particularly vascular thrombotic events are vital.

HSA-based multi-target combination therapy: regulating drugs' release from HSA and overcoming single drug resistance in a breast cancer model.

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Gou, Yi; Zhang, Zhenlei; Li, Dongyang; Zhao, Lei; Cai, Meiling; Sun, Zhewen; Li, Yongping; Zhang, Yao; Khan, Hamid; Sun, Hongbing; Wang, Tao; Liang, Hong; Yang, Feng

2018-11-01

Multi-drug delivery systems, which may be promising solution to overcome obstacles, have limited the clinical success of multi-drug combination therapies to treat cancer. To this end, we used three different anticancer agents, Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)-based multi-drug delivery systems in a breast cancer model to investigate the therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells in vivo, and to regulate the drugs' release from HSA. The HSA complex structure revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N-donor residue replacing a leaving group and coordinating to their metal centers, respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release behavior of three agents form HSA can be regulated at different pH levels. Importantly, in vivo results revealed that the HSA-NAMI-A-Cu(BpT)Br-DOX complex not only increases the targeting ability compared with a combination of the three agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance to drug-resistant breast cancer cell lines.

Emerging drugs for the treatment of obesity

DEFF Research Database (Denmark)

Martinussen, Christoffer; Bojsen-Møller, Kirstine Nyvold; Svane, Maria Saur

2017-01-01

INTRODUCTION: 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...

Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

Science.gov (United States)

Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

2016-11-01

 The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Botanical and phytochemical therapy of acne: a systematic review.

Science.gov (United States)

Fisk, Whitney A; Lev-Tov, Hadar A; Sivamani, Raja K

2014-08-01

Acne is prevalent among adolescents and adults with significant psychological effects. Standard oral and topical therapies can have significant side effects including skin irritation, gastrointestinal upset, and the development of drug-resistant bacteria. The use of botanicals and phytochemicals in dermatological products is increasingly popular, and many patients are turning to these alternative therapies for treatment of acne. This study aimed to systematically review clinical studies that have investigated the use of botanical agents in the treatment of acne. PubMed and Embase databases were searched in March 2013 for trials assessing botanical therapies in the treatment of acne vulgaris. Data from these trials are presented, and methodology of each study is assessed. Twenty-three trials met inclusion criteria. Interventions included plant extracts, herbal formulations, and phytochemicals. All studies reported favorable results, and several showed equal or superior treatment to standard therapies. No serious adverse events were reported. Few studies were methodologically rigorous. Each botanical was studied in only one or two trials. Botanicals are promising therapies for acne vulgaris although further research is warranted, especially with regard to severe acne and acne resistant to conventional therapy. There is a need for standardized methods for grading acne and assessing therapeutic effects. Copyright © 2014 John Wiley & Sons, Ltd.

Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

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Wang ZY

2015-03-01

inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole, the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers. The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4, paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.Conclusion: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring. Keywords: clopidogrel, drug–drug interactions, drug metabolism, drug transporter, genotype, pharmacokinetics, polypharmacy, pharmacogenetics, P2Y12 receptor inhibitors, risk management 

On the MTD paradigm and optimal control for multi-drug cancer chemotherapy.

Science.gov (United States)

Ledzewicz, Urszula; Schättler, Heinz; Gahrooi, Mostafa Reisi; Dehkordi, Siamak Mahmoudian

2013-06-01

In standard chemotherapy protocols, drugs are given at maximum tolerated doses (MTD) with rest periods in between. In this paper, we briey discuss the rationale behind this therapy approach and, using as example multidrug cancer chemotherapy with a cytotoxic and cytostatic agent, show that these types of protocols are optimal in the sense of minimizing a weighted average of the number of tumor cells (taken both at the end of therapy and at intermediate times) and the total dose given if it is assumed that the tumor consists of a homogeneous population of chemotherapeutically sensitive cells. A 2-compartment linear model is used to model the pharmacokinetic equations for the drugs.

Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

International Nuclear Information System (INIS)

2017-01-01

Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

International Nuclear Information System (INIS)

2017-01-01

Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

Directory of Open Access Journals (Sweden)

Nathan W Kopper

2008-10-01

Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

Effect of acupuncture combined with drug therapy on the nerve cytokine secretion and oxidative stress in convalescence of cerebral infarction

Directory of Open Access Journals (Sweden)

Xiao-Jie Dai

2017-09-01

Full Text Available Objective: To explore the effect of acupuncture combined with drug therapy on the nerve cytokine secretion and oxidative stress in convalescence of cerebral infarction. Methods: A total of 118 patients in convalescence of cerebral infarction who were treated in the affiliated hospital of our school between August 2014 and December 2016 were divided into control group (n=59 and observation group (n=59 according to the random number table method. Control group received routine drug therapy, and the observation group received acupuncture combined with drug therapy. The differences in serum levels of neurotrophic factors, nerve injury factors and oxidative stress indexes were compared between the two groups before and after treatment. Results: The differences in serum levels of neurotrophic factors, nerve injury factors and oxidative stress indexes were not statistically significant between the two groups before treatment. After treatment, serum neurotrophic factors IGF-1, BDNF and NGF levels of observation group were higher than those of control group; nerve injury factors S-100β, NSE, GFAP and UCH-L1 levels were lower than those of control group; oxidative stress indexes MDA, AOPPs and LHP levels were lower than those of control group while SOD and GSH-Px levels were higher than those of control group. Conclusion: Acupuncture combined with drug therapy can effectively optimize the nerve function, reduce the nerve injury and suppress the systemic oxidative stress response of patients in convalescence of cerebral infarction.

Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy

Science.gov (United States)

Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.

2014-01-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

Science.gov (United States)

Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

2016-06-14

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

Simulated Prism Therapy in Virtual Reality produces larger after-effects than standard prism exposure in normal healthy subject - Implications for Neglect Therapy

DEFF Research Database (Denmark)

Wilms, Inge Linda

2018-01-01

BACKGROUND: Virtual reality is an important area of exploration within computer-based cognitive rehabilitation of visual neglect. Virtual reality will allow for closer monitoring of patient behaviour during prism adaptation therapy and perhaps change the way we induce prismatic after......-effects. OBJECTIVE: This study compares the effect of two different prism simulation conditions in virtual reality to a standard exposure to prism goggles after one session of Prism Adaptation Therapy in healthy subjects. METHOD: 20 healthy subjects were subjected to one session of prism adaptation therapy under...... training for rehabilitation of hemi spatial attentional deficits such as visual neglect....

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

Directory of Open Access Journals (Sweden)

Farrar Jeremy

2011-02-01

Full Text Available Abstract Background In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design. Methods We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. Results In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Conclusions Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of

Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

Science.gov (United States)

Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

2014-01-01

The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (ptextbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education. PMID:25250889

Hyperactivity--Drug Therapy/Food Additives/Allergies. A Selective Bibliography. Exceptional Child Bibliography Series No. 602.

Science.gov (United States)

ERIC Clearinghouse on Handicapped and Gifted Children, Reston, VA.

The annotated bibliography on Hyperactivity--Drug Therapy/Food Additives/Allergies contains approximately 65 abstracts and associated indexing information for documents or journal articles published from 1968 to 1975 and selected from the computer files of the Council for Exceptional Children's Information Services and the Education Resources…

Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

Directory of Open Access Journals (Sweden)

Meigs James B

2009-02-01

Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

Evaluation of short course drug therapy for tuberculosis in pediatric ward of Imam Khomeini Hospital

Directory of Open Access Journals (Sweden)

Daneshjoo Kh

1999-07-01

Full Text Available Tuberculosis appears to be a disease as old as human history. Tuberculosis is of great public health importance in the developing countries. Its clinical profile is different in developing countries in comparison to countries of Europe and North America. The recent epidemic of HIV has slowed down the declining trend in the incidence of tuberculosis. Bacilli are transmitted from one infected person to the others as an aerosol. In some cases contaminated milk may also be responsible. However despite effective regimens and addition of new drugs and improved pharmacokinetic knowledge the chemotherapy of tuberculosis still remains a challenge. Poor drug-compliance by patients being one of the foremost reason for frequent relapses and bacterial resistance. Some important and concrete steps to meet these challenges have been judicious use of two or more bactericidal drugs and introduction of short courses regiment. Multiple drugs therapy may shorten the duration of treatment and prevent emergence of drug resistance.

ADEpedia: a scalable and standardized knowledge base of Adverse Drug Events using semantic web technology.

Science.gov (United States)

Jiang, Guoqian; Solbrig, Harold R; Chute, Christopher G

2011-01-01

A source of semantically coded Adverse Drug Event (ADE) data can be useful for identifying common phenotypes related to ADEs. We proposed a comprehensive framework for building a standardized ADE knowledge base (called ADEpedia) through combining ontology-based approach with semantic web technology. The framework comprises four primary modules: 1) an XML2RDF transformation module; 2) a data normalization module based on NCBO Open Biomedical Annotator; 3) a RDF store based persistence module; and 4) a front-end module based on a Semantic Wiki for the review and curation. A prototype is successfully implemented to demonstrate the capability of the system to integrate multiple drug data and ontology resources and open web services for the ADE data standardization. A preliminary evaluation is performed to demonstrate the usefulness of the system, including the performance of the NCBO annotator. In conclusion, the semantic web technology provides a highly scalable framework for ADE data source integration and standard query service.

Cost-effectiveness of computer-assisted training in cognitive-behavioral therapy as an adjunct to standard care for addiction.

Science.gov (United States)

Olmstead, Todd A; Ostrow, Cary D; Carroll, Kathleen M

2010-08-01

To determine the cost-effectiveness, from clinic and patient perspectives, of a computer-based version of cognitive-behavioral therapy (CBT4CBT) as an addition to regular clinical practice for substance dependence. PARTICIPANTS, DESIGN AND MEASUREMENTS: This cost-effectiveness study is based on a randomized clinical trial in which 77 individuals seeking treatment for substance dependence at an outpatient community setting were randomly assigned to treatment as usual (TAU) or TAU plus biweekly access to computer-based training in CBT (TAU plus CBT4CBT). The primary patient outcome measure was the total number of drug-free specimens provided during treatment. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves (CEACs) were used to determine the cost-effectiveness of TAU plus CBT4CBT relative to TAU alone. Results are presented from both the clinic and patient perspectives and are shown to be robust to (i) sensitivity analyses and (ii) a secondary objective patient outcome measure. The per patient cost of adding CBT4CBT to standard care was $39 ($27) from the clinic (patient) perspective. From the clinic (patient) perspective, TAU plus CBT4CBT is likely to be cost-effective when the threshold value to decision makers of an additional drug-free specimen is greater than approximately $21 ($15), and TAU alone is likely to be cost-effective when the threshold value is less than approximately $21 ($15). The ICERs for TAU plus CBT4CBT also compare favorably to ICERs reported elsewhere for other empirically validated therapies, including contingency management. TAU plus CBT4CBT appears to be a good value from both the clinic and patient perspectives. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Effective experimental tumor therapy with targeted polymer drug delivery systems based on HPMA copolymers.

Czech Academy of Sciences Publication Activity Database

Šírová, Milada; Horková, Veronika; Sivák, Ladislav; Etrych, Tomáš; Říhová, Blanka; Studenovský, Martin

SI (2016), s. 24-24 ISSN 0014-2980. [3rd Meeting of Middle – European Societies for Immunology and Allergology. 01.12.2016-03.12.2016, Budapest ] R&D Projects: GA ČR(CZ) GA14-12742S Institutional support: RVO:61388971 ; RVO:61389013 Keywords : Tumor therapy * polymer drug * HPMA copolymers Subject RIV: EE - Microbiology, Virology

Adolescent and parent alliances with therapists in Brief Strategic Family Therapy with drug-using Hispanic adolescents.

Science.gov (United States)

Robbins, Michael S; Mayorga, Carla C; Mitrani, Victoria B; Szapocznik, José; Turner, Charles W; Alexander, James F

2008-07-01

This study examined the relationship between alliance and retention in family therapy. Alliance was examined at the individual (parent, adolescent) and family level (within-family differences) for families that either dropped out or completed family therapy. Participants were 31 Hispanic adolescents and their family members who received brief strategic family therapy for the treatment of adolescent drug use. Videotapes of first sessions were rated to identify parent and adolescent alliances with the therapist. Results demonstrated that Completer cases had significantly higher levels of alliance across all family members than Dropout cases, and Dropout cases had significantly higher unbalanced alliances than Completer cases. Clinical implications are discussed.

131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment

Science.gov (United States)

Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

2015-01-01

The aim of this study is to evaluate the safety and long-term results of 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with 131I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to 131I therapy, all patients were given low-iodine diet. The dose of 131I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total 131I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that 131I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. PMID:26341470

131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment.

Science.gov (United States)

Ding, Yong; Xing, Jialiu; Fang, Yi; Wang, Yong; Zhang, Youren; Long, Yahong

2016-02-01

The aim of this study is to evaluate the safety and long-term results of (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with (131)I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to (131)I therapy, all patients were given low-iodine diet. The dose of (131)I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total (131)I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective. © 2015 by the Society for Experimental Biology and Medicine.

Adding chiropractic to standard medical therapy for nonspecific low back pain

DEFF Research Database (Denmark)

Goertz, Christine M; Long, Cynthia R; Hondras, Maria

2013-01-01

Study Design. Randomized controlled trial.Objective. To assess changes in pain levels and physical functioning in response to standard medical care (SMC) versus SMC plus chiropractic manipulative therapy (CMT) for the treatment of low back pain (LBP) among 18 to 35-year-old active-duty military...... physical functioning when compared with only standard care, for men and women between 18 and 35 years of age with acute LBP........ The primary outcome measures were changes in back-related pain on the numerical rating scale and physical functioning at 4 weeks on the Roland-Morris Disability Questionnaire and back pain functional scale (BPFS).Results. Mean Roland-Morris Disability Questionnaire scores decreased in both groups during...

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

Directory of Open Access Journals (Sweden)

Unterweger H

2015-11-01

Full Text Available Harald Unterweger,1 Daniel Subatzus,1 Rainer Tietze,1 Christina Janko,1 Marina Poettler,1 Alfons Stiegelschmitt,2 Matthias Schuster,3 Caroline Maake,4 Aldo R Boccaccini,5 Christoph Alexiou11ENT Department, Section of Experimental Oncology and Nanomedicine (SEON, Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen; 2Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, 3Materials for Electronics and Energy Technology, Department of Materials Science and Engineering, University Erlangen-Nürnberg, Erlangen, Germany; 4Institute of Anatomy, University of Zurich, Winterthurerstr, Zurich, Switzerland; 5Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany Abstract: Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55–85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5–5.0 nm. Surface chemistry of those

Antiherpetic Drugs in Equine Medicine.

Science.gov (United States)

Maxwell, Lara K

2017-04-01

Since vaccination may not prevent disease, antiherpetic drugs have been investigated for the therapy of several equine herpesviruses. Drug efficacy has been assessed in horses with disease, but most evidence is in vitro, in other species, or empirical. Oral valacyclovir is most often administered in the therapy of equine herpesvirus type-1 (EHV-1) to protect adult horses from equine herpesvirus myeloencephalopathy, while oral acyclovir is frequently administered for EHV-5 infection in the therapy of equine multinodular pulmonary fibrosis. Other antiherpetic drugs are promising but require further investigation. Several topical drugs are also empirically used in the therapy of equine viral keratitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of music therapy in state-trait anxiety rate of addicts in drug-free rehabilitation stage

Directory of Open Access Journals (Sweden)

E Soleimani

2016-02-01

Full Text Available Objective: This study was an attempt to investigate the effect of music therapy on addicts’ state-trait anxiety rate in the stage of drug-free rehabilitation. Method: A quasi-experimental research design, along with pretest-posttest and control group was employed for the conduct of this study. The statistical population of the study included the addicts in the rehabilitation stage who had referred to the clean collaborators rehabilitation camp in Ardebil province in November 2014. From this population, the number of 32 addicts in 16-50-year-old age range was selected as the participants of the study by convenience sampling method. State-Trait Anxiety Inventory was used for data collection. Results: The results of multivariate covariant analysis showed that there is a significant difference between control and experimental groups in state and trait anxiety. In other words, the state and trait anxiety of addicts in the experimental group had been reduced after music therapy. Conclusion: Considering the obtained results, it can be concluded that music therapy alone or along other psychological interventions can be an effective method for reducing addicts’ anxiety in drug-free rehabilitation stage.

Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia.

Science.gov (United States)

Vijay, Aishwarya; Bazazi, Alexander R; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L

2015-07-01

Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experiences with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (polder age (ppeople who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics aimed at improving entry into and retention in treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Biologic Drugs: A New Target Therapy in COPD?

Science.gov (United States)

Yousuf, Ahmed; Brightling, Christopher E

2018-04-23

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria based on the presence of fixed airflow obstruction and symptoms do not integrate the complex pathological changes occurring within the lung and they do not define different airway inflammatory patterns. The current management of COPD is based on 'one size fits all' approach and does not take the importance of heterogeneity in COPD population into account. The available treatments aim to alleviate symptoms and reduce exacerbation frequency but do not alter the course of the disease. Recent advances in molecular biology have furthered our understanding of inflammatory pathways in pathogenesis of COPD and have led to development of targeted therapies (biologics and small molecules) based on predefined biomarkers. Herein we shall review the trials of biologics in COPD and potential future drug developments in the field.

Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

Science.gov (United States)

Simoens, Steven

2011-01-01

This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

[Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams].

Science.gov (United States)

Yokaichiya, Chizuru Minami; Figueiredo, Wagner dos Santos; Schraiber, Lilia Blima

2007-12-01

To understand the perceptions of pharmacy teams about their role in the healthcare assistance challenges and adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

Clinical Management of HIV Drug Resistance

Science.gov (United States)

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

How we make cell therapy in Italy

Directory of Open Access Journals (Sweden)

Montemurro T

2015-08-01

Full Text Available Tiziana Montemurro, Mariele Viganò, Silvia Budelli, Elisa Montelatici, Cristiana Lavazza, Luigi Marino, Valentina Parazzi, Lorenza Lazzari, Rosaria GiordanoCell Factory, Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyAbstract: In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.Keywords: advanced therapy medicinal product, good manufacturing practices, stem cells

RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

D E Karateev

2008-01-01

Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

Development of job standards for clinical nutrition therapy for dyslipidemia patients.

Science.gov (United States)

Kang, Min-Jae; Seo, Jung-Sook; Kim, Eun-Mi; Park, Mi-Sun; Woo, Mi-Hye; Ju, Dal-Lae; Wie, Gyung-Ah; Lee, Song-Mi; Cha, Jin-A; Sohn, Cheong-Min

2015-04-01

Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

Directory of Open Access Journals (Sweden)

Jona Kräenbring

Full Text Available The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001. Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001 and highest in the category "indication" (91.3% ± 2.0% when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

Science.gov (United States)

Kräenbring, Jona; Monzon Penza, Tika; Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

2014-01-01

The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001). Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001) and highest in the category "indication" (91.3% ± 2.0%) when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

Pharmacokinetic drug-drug interaction and their implication in clinical management

OpenAIRE

Palleria, Caterina; DI PAOLO, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2013-01-01

Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In thi...

Dual drug encapsulated thermo-sensitive fibrinogen-graft-poly (N-isopropyl acrylamide) nanogels for breast cancer therapy.

Science.gov (United States)

Rejinold, N Sanoj; Baby, Thejus; Chennazhi, K P; Jayakumar, R

2014-02-01

5-FU/Megestrol acetate loaded fibrinogen-graft-PNIPAAm Nanogels (5-FU/Meg-fib-graft-PNIPAAm NGs) were prepared for thermo responsive drug delivery toward α5β1-integrins expressing breast cancer cells in vitro (MCF-7 cells). The 60-100 nm sized fib-graft-PNIPAAm nanogels (LCST=35 °C) were prepared by CaCl2 cross-linker. 5-FU/Meg-fib-graft-PNIPAAm NGs showed particle size of 165-195 nm size. The drug loading efficiency with 5-FU was 60% and 70% for Meg. "Drug release was greater above the lower critical solution temperature (LCST). Above LCST, drug release system triggers apopotosis and enhance toxicity to MCF-7 cells when compared to the equivalent dose of the free drug. This effect was due to the greater uptake of the drug by MCF-7 cells". 5-FU/Meg-fib-graft-PNIPAAm NGs is portrayed here as a new combinatorial thermo-responsive drug delivery agent for breast cancer therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

A Study of the Trend and Extent of Drug Abuse Among Drug ...

African Journals Online (AJOL)

The findings show that drug-abusers are predominantly males, single, unskilled workers, traders, unemployed and civil servants. Psychiatric hospitals and rehabilitation centres served as treatment centres for participants with previous admission records. Drug therapy, psychotherapy and occupational therapy were the ...

Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Caixia; Ye, Yuqiu; Liu, Chunyong; Zhou, Yongming; Lv, Linsheng; Cheng, Cailian; Li, Shaomin; Lou, Tanqi; Liu, Xun

2017-08-01

Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients. © 2017 Royal Australasian College of Physicians.

Comparative effectiveness of oral drug therapies for lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and network meta-analysis.

Directory of Open Access Journals (Sweden)

Xinghuan Wang

Full Text Available Lower urinary tract symptoms (LUTS due to benign prostatic hyperplasia (BPH are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs plus phosphodiesterase 5 inhibitors (PDE5-Is ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax with a mean difference (MD of 1.98 (95% CI, 1.12 to 2.86 as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other

Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

International Nuclear Information System (INIS)

Hinkle, G.H.; Basmadjian, G.P.; Peek, C.; Barker, K.K.; Ice, R.D.

1982-01-01

Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate

Medical-legal aspects of the fungal infection drug therapy in neonatology: evidence-based medicine and off-label prescribing

Directory of Open Access Journals (Sweden)

Marta Ciuffi

2014-06-01

Full Text Available The aim of this paper is to focus on the well-known issue of the clinical use of off-label drug therapy in neonatology with respect to evidence-based medicine, with particular reference to antifungal products, in comparison with the wider use in pediatric and adult population. Then we considered the new regulatory approaches carried out in the past decade by the FDA (Food and Drug Administration and the EMA (European Medicine Agency, aimed to improve newborn and children population inclusion into scientific trials and to promote drug labeling with respect to pediatric indications, and the goals nowadays achieved through the American Pediatric Research Equity Act / Best Pharmaceuticals for Children Act and the European Pediatric Investigation Plans. Finally we pointed out, on the basis of the Italian regulatory framework, the Italian medical-legal liability profiles related to the use of off-label therapies in neonatology. Further efforts are required in the international context to carry forward the process started while in the particular Italian scenario it is to be hoped that a general change of mind towards the off-label drug use in neonatology clinical practice may take place.

Novel drugs targeting Toll-like receptors for antiviral therapy.

Science.gov (United States)

Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

2014-09-01

Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

[Cognitive-behavioral therapy for alcohol and drug use disorders].

Science.gov (United States)

Rangé, Bernard P; Marlatt, G Alan

2008-10-01

Cognitive-behavioral therapies have been successfully used to treat addiction. This article is in part a review on addiction models such as relapse prevention by Marlatt & Gordon, stages of change by Prochaska, DiClemente & Norcross, deriving from motivational interview, developed by Miller & Rollnick, as well as the cognitive models by Beck et al. Based on literature evidence for the development of effective treatment programs, we report on a group treatment model used in a group of alcoholics referred by the Department of Worker's Health Surveillance at Universidade Federal do Rio de Janeiro to the Alcoholism Rehabilitation and Research Center. Results are presented indicating that this type of treatment could be one alternative to others treatments in use. New research is needed to better validate cognitive-behavioral approach to alcohol and drug problems.

Review of Real-Time 3-Dimensional Image Guided Radiation Therapy on Standard-Equipped Cancer Radiation Therapy Systems: Are We at the Tipping Point for the Era of Real-Time Radiation Therapy?

Science.gov (United States)

Keall, Paul J; Nguyen, Doan Trang; O'Brien, Ricky; Zhang, Pengpeng; Happersett, Laura; Bertholet, Jenny; Poulsen, Per R

2018-04-14

To review real-time 3-dimensional (3D) image guided radiation therapy (IGRT) on standard-equipped cancer radiation therapy systems, focusing on clinically implemented solutions. Three groups in 3 continents have clinically implemented novel real-time 3D IGRT solutions on standard-equipped linear accelerators. These technologies encompass kilovoltage, combined megavoltage-kilovoltage, and combined kilovoltage-optical imaging. The cancer sites treated span pelvic and abdominal tumors for which respiratory motion is present. For each method the 3D-measured motion during treatment is reported. After treatment, dose reconstruction was used to assess the treatment quality in the presence of motion with and without real-time 3D IGRT. The geometric accuracy was quantified through phantom experiments. A literature search was conducted to identify additional real-time 3D IGRT methods that could be clinically implemented in the near future. The real-time 3D IGRT methods were successfully clinically implemented and have been used to treat more than 200 patients. Systematic target position shifts were observed using all 3 methods. Dose reconstruction demonstrated that the delivered dose is closer to the planned dose with real-time 3D IGRT than without real-time 3D IGRT. In addition, compromised target dose coverage and variable normal tissue doses were found without real-time 3D IGRT. The geometric accuracy results with real-time 3D IGRT had a mean error of real-time 3D IGRT methods using standard-equipped radiation therapy systems that could also be clinically implemented. Multiple clinical implementations of real-time 3D IGRT on standard-equipped cancer radiation therapy systems have been demonstrated. Many more approaches that could be implemented were identified. These solutions provide a pathway for the broader adoption of methods to make radiation therapy more accurate, impacting tumor and normal tissue dose, margins, and ultimately patient outcomes. Copyright © 2018

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

OpenAIRE

de Lange, Elizabeth CM

2013-01-01

Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

Family Advocacy Program Standards and Self-Assessment Tool

Science.gov (United States)

1992-08-01

Adults and Adolescents. 6. Drug and Alcohol Counseling. 7. Family Therapy. 8. Conjoint Therapy for Couples. 9. Play Therapy for Children. 10. Victims...Older Children. 6. Drug and Alcohol Counseling. 7. Family Therapy. 8. Conjoint Therapy for Couples. 9. Play Therapy for Children. PS 5.33: Clinically

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

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Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

2017-08-01

Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross

Failure of Chemotherapy in Hepatocellular Carcinoma Due to Impaired and Dysregulated Primary Liver Drug Metabolizing Enzymes and Drug Transport Proteins: What to Do?

Science.gov (United States)

Ul Islam, Salman; Ahmed, Muhammad Bilal; Shehzad, Adeeb; Ul-Islam, Mazhar; Lee, Young Sup

2018-05-28

Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes. In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical resection, and locoregional therapies. This review details the dysregulation of primary drug metabolizing enzymes and drug transport proteins of the liver in HCC and their influence on chemotherapeutic drugs. Furthermore, it emphasizes the adoption of safe alternative therapeutic strategies to chemotherapy. The future of HCC treatment should emphasize the understanding of resistance mechanisms and the finding of novel, safe, and efficacious therapeutic strategies, which will surely benefit patients affected by advanced HCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intra-articular therapies for osteoarthritis.

Science.gov (United States)

Yu, Shirley P; Hunter, David J

2016-10-01

Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.

Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

Directory of Open Access Journals (Sweden)

Haeberle Anne

2012-09-01

Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.

Science.gov (United States)

Unterweger, Harald; Subatzus, Daniel; Tietze, Rainer; Janko, Christina; Poettler, Marina; Stiegelschmitt, Alfons; Schuster, Matthias; Maake, Caroline; Boccaccini, Aldo R; Alexiou, Christoph

2015-01-01

Combining the concept of magnetic drug targeting and photodynamic therapy is a promising approach for the treatment of cancer. A high selectivity as well as significant fewer side effects can be achieved by this method, since the therapeutic treatment only takes place in the area where accumulation of the particles by an external electromagnet and radiation by a laser system overlap. In this article, a novel hypericin-bearing drug delivery system has been developed by synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) with a hypericin-linked functionalized dextran coating. For that, sterically stabilized dextran-coated SPIONs were produced by coprecipitation and crosslinking with epichlorohydrin to enhance stability. Carboxymethylation of the dextran shell provided a functionalized platform for linking hypericin via glutaraldehyde. Particle sizes obtained by dynamic light scattering were in a range of 55-85 nm, whereas investigation of single magnetite or maghemite particle diameter was performed by transmission electron microscopy and X-ray diffraction and resulted in approximately 4.5-5.0 nm. Surface chemistry of those particles was evaluated by Fourier transform infrared spectroscopy and ζ potential measurements, indicating successful functionalization and dispersal stabilization due to a mixture of steric and electrostatic repulsion. Flow cytometry revealed no toxicity of pure nanoparticles as well as hypericin without exposure to light on Jurkat T-cells, whereas the combination of hypericin, alone or loaded on particles, with light-induced cell death in a concentration and exposure time-dependent manner due to the generation of reactive oxygen species. In conclusion, the combination of SPIONs' targeting abilities with hypericin's phototoxic properties represents a promising approach for merging magnetic drug targeting with photodynamic therapy for the treatment of cancer.

Integrity, standards, and QC-related issues with big data in pre-clinical drug discovery.

Science.gov (United States)

Brothers, John F; Ung, Matthew; Escalante-Chong, Renan; Ross, Jermaine; Zhang, Jenny; Cha, Yoonjeong; Lysaght, Andrew; Funt, Jason; Kusko, Rebecca

2018-06-01

The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development. We describe standardized approaches for maximizing the utility of publicly available or privately generated biological data and address some of the common pitfalls. We also discuss the increasing interest to integrate and interpret cross-platform data. Principles outlined here should serve as a useful broad guide for existing analytical practices and pipelines and as a tool for developing additional insights into therapeutics using big data. Copyright © 2018 Elsevier Inc. All rights reserved.

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

Science.gov (United States)

Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

2009-01-01

Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles

Science.gov (United States)

Baek, Seonmi; Singh, Rajendra K.; Khanal, Dipesh; Patel, Kapil D.; Lee, Eun-Jung; Leong, Kam W.; Chrzanowski, Wojciech; Kim, Hae-Won

2015-08-01

Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.

A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

International Nuclear Information System (INIS)

Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong

2009-01-01

In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

Energy Technology Data Exchange (ETDEWEB)

Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong, E-mail: Zheng-qx@163.co [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

2009-12-15

In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

Challenges and perspectives of compliance with pediatric antiretroviral therapy in Sub-Saharan Africa.

Science.gov (United States)

Dahourou, D L; Leroy, V

2017-12-01

More than 3 million children aged less than 15years are infected with HIV worldwide, mainly in Sub-Saharan Africa. The survival of HIV-infected children depends on their access to antiretroviral therapy whose success mainly depends on a good life-long compliance with antiretroviral therapy. Given its complexity and specificity, assessment and monitoring of pediatric compliance with antiretroviral therapy is a major challenge. There is no consensus on a gold standard for monitoring compliance with antiretroviral therapy. Compliance is also influenced by many factors related to the child, the caregiver, the healthcare staff, the healthcare system, and antiretroviral drugs. This review aimed to assess scientific knowledge on pediatric compliance with antiretroviral therapy in Sub-Saharan Africa, and to identify areas for future interventions to improve compliance. Good compliance is essential to achieve the "90% coverage of children on antiretroviral therapy" gold standard of the World Health Organization, and to eliminate HIV infection by 2030. Copyright © 2017. Published by Elsevier SAS.

Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

International Nuclear Information System (INIS)

Weissman, Ben Avi; Raveh, Lily

2008-01-01

Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission

HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

Directory of Open Access Journals (Sweden)

Kazuaki Chayama

2015-10-01

Full Text Available Sustained virological response (SVR rates have increased dramatically following the approval of direct acting antiviral (DAA therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.

Patient compliance with drug therapy in schizophrenia. Economic and clinical issues.

Science.gov (United States)

Lindström, E; Bingefors, K

2000-08-01

The effectiveness of drug treatment in clinical practice is considerably lower than the efficacy shown in controlled studies. The lower effectiveness in practice presumably leads to lower cost effectiveness of drug treatment in real-life situations compared with that demonstrated by studies based on results from controlled trials. Improved cost effectiveness in routine clinical practice would be a significant advantage in the treatment of schizophrenia, one of the most costly diseases in society. The aetiology of schizophrenia is unknown, and there is no cure. The main aims of therapy with antipsychotic medication include the effective relief of symptoms without the introduction of adverse effects or serious adverse events, improved quality of life, cost effectiveness and a positive long term outcome. The older classical antipsychotic drugs do not always meet these requirements because of their well-known limitations, such as a lack of response in a subgroup of individuals with schizophrenia and intolerable adverse effects. There has long been a need for new antipsychotics that can ameliorate more symptoms and have no or few adverse effects. Some of the recently introduced antipsychotics have been shown to be more effective in certain clinical situations and to have a more favourable adverse effect profile than the classical antipsychotics. A major factor contributing to the lower effectiveness of drug treatment is noncompliance, which may be very high in schizophrenia. There are several factors influencing compliance, including drug type and formulation, patient, disease status, physician, health care system, community care and family. There have been very few studies of compliance improvement strategies in schizophrenia or, indeed, in medicine in general. Current methods are relatively complex and there are differing opinions on their effectiveness. There are several ways to increase compliance in schizophrenia--the evidence is strongest for psychoeducative

Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

Science.gov (United States)

Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

2013-10-01

Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users